Patent Publication Number: US-2023139131-A1

Title: Sheet Lighting for Particle Detection in Drug Product Containers

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This is a continuation of U.S. patent application Ser. No. 17/414,544, which is a national stage application based on PCT Patent Application No. PCT/US19/66458, filed Dec. 16, 2019, which claims the benefit U.S. Provisional Patent Application No. 62/780,542, filed Dec. 17, 2018. The entire disclosure of each of the above-identified applications is hereby incorporated herein by reference. 
    
    
     FIELD OF DISCLOSURE 
     The present application relates generally to particle detection techniques, and more specifically to particle detection techniques capable of distinguishing particles within a container (e.g., syringe, vial, etc.) from particles on the outside surface of the container. 
     BACKGROUND 
     Foreign particles in drug product containers pose a serious health and safety risk for patients, particularly with respect to injected drug products. While automated visual inspection equipment can in some cases detect particles in containers holding liquid products with acceptable accuracy, there can be a large number of false rejects, e.g., due to small particles and blemishes on the exterior of the container wall, defects on the interior of the container wall or in the bulk of the container wall (e.g., cracks), and/or small bubbles on the inside of the container wall. 
     A conventional imaging system  100  is shown in  FIG.  1   . As seen in  FIG.  1   , a container  102  filled with a sample (e.g., liquid drug product) is illuminated by two angled lights  104 A and  104 B, which are positioned so as to generally oppose a camera  106  on the other side of container  102 . Lights  104 A and  104 B are directional, with most of the emitted light propagating in a direction orthogonal to the planar surfaces shown in  FIG.  1    (i.e., as shown by the arrows in  FIG.  1   ). This requires that each of lights  104 A,  104 B be large enough to evenly illuminate the entire container. Since most of the emitted light is not directed at the lens of camera  106 , the resulting image is a dark background against bright particles, if any particles exist.  FIG.  2    depicts another conventional imaging system  200  that is typically used for larger, opaque particles (over 500 um), or fibers that might be stuck to the inside wall of the container. As seen in  FIG.  2   , container  202  is illuminated by a back light  204 , opposite camera  206 . In this case, camera  206  images the shadow cast by a particle, and the particle appears as a black object against a relatively bright background. 
     A problem with both of these conventional illumination approaches is that the entire container is flooded with light, such that particles and surface blemishes on both the inside and the outside of the container are illuminated. As a result, it can be difficult to distinguish particles inside the container from particles outside the container. Because particles outside the container may not be relevant to a quality control procedure, this difficulty heightens the risk of false positives. For rear, angled light arrangements such as imaging system  100 , a technique known as “image subtraction,” or “minimum intensity projection” (MIP), is commonly used to distinguish smaller particles (˜100-500 um) inside the container from particles outside the container. This technique involves spinning the container about its central axis at high speed (˜600-5000 RPM), stopping the spinning abruptly, acquiring a series of images of the stopped container at approximately 10 to 50 ms intervals, and then subtracting subsequent images such that only those objects that moved between images appear in the resulting difference image. This effectively cancels out the small particles and surface blemishes that may be on the outside of the container, while highlighting objects that are suspended in, and carried by the momentum of, the liquid in the container. However, this technique may be inadequate for highly viscous drug products, as there may be very little or no motion of the fluid and particles after the container stops spinning. Back-lit arrangements such as imaging system  200  also have drawbacks, as they can “bleach out” small particles, or particles that are not opaque, and generally depend on particles inside the container being large enough to be distinguished from the smaller particles that typically reside on the exterior surface of containers. 
     Some manufacturers of automated inspection equipment for pharmaceutical products have proposed, and implemented, techniques that attempt to address these problems. For example, U.S. Pat. No. 8,036,444 (Nielsen), entitled “Method and System for Irradiating and Inspecting Liquid-Carrying Containers,” describes an imaging system in which two line scan cameras generate flattened images of a spinning container. One camera is aligned with the central axis of the container, while the other camera is offset from the central axis. The technique leverages the basic principle that, when the container is rotated, particles on the outside of a container will move a longer distance horizontally (i.e., in a direction orthogonal to the container central axis) than particles inside the container. Images from the two line scan cameras are compared after multiple images have been acquired at different rotations, and the distances between particles are computed. This distance can in some cases be used to distinguish particles on the inside and outside of the container. 
     As another example, European Patent No. 3,062,292 (Kwoka), entitled “Inspection Method and Inspection Device for Monitoring Production Processes,” describes an imaging system that uses a single area scan camera. When a particle is detected at a position along the central axis of the container, the position is digitally shifted to a point where it would be if it were on the outside of the container and the container were precisely rotated about its central axis a preset angle (˜45°. The container is then rotated and a new image is taken. If the particle is in fact on the outside of the container, it should overlap with the digitally shifted image. If the particle is instead inside the container, it will be offset from the digitally shifted particle by some amount. 
     While the techniques of U.S. Pat. No. 8,036,444 (Nielsen) and European Patent No. 3,062,292 (Kwoka) may improve upon the conventional image subtraction method described above in some respects, both approaches have significant drawbacks of their own. One difficulty is that, with both approaches, any slight vibration of the container between images can cause significant errors. Moreover, if a particle on the inside of the container “slips” while the container is rotated, it may not be in the expected position to be properly detected. Furthermore, limitations on the spatial resolution of imagers may make the techniques insufficient to distinguish small blemishes inside the glass, which can be a large source of false rejects. 
     Further, while promising 3D imaging techniques are being developed and offer the ability to determine particle size and morphology from images, they are very computationally expensive, and may not work at typical manufacturing line rates (e.g., 300 to 600 containers per minute). Accordingly, there remains a need for improved methods to detect particles inside liquid-filled drug product containers, particularly (but not only) for containers holding highly viscous samples/products. 
     SUMMARY 
     Embodiments described herein relate to systems and methods that improve upon conventional automated visual inspection techniques. In particular, an imaging system illuminates a container with a relatively thin sheet of laser light, with the laser sheet impinging upon the container from a direction substantially orthogonal to the imaging axis of the camera. The laser sheet may pass through the central axis of the container, for example. With this lighting configuration, particles can only be seen in the resulting image (or can only be seen with a certain intensity level, etc.) if those particles are within the thickness of the laser sheet. Thus, by using the laser sheet and the orthogonal orientation of the camera, it can easily be determined whether a particle seen in an image is inside or outside of the container: any imaged particles that are outside the container will be outside the container walls in the image, and any imaged particles that are inside the container will be between the container walls in the image. 
     In some embodiments, the container is rotated a number of times about its central axis, and imaged at each rotation while the laser sheet is still applied, in order to inspect the entire volume of the drug product (or other sample) within the container. While numerous rotations may be required, the image processing and computational load can be very light, and the probability of false rejects can be very low. Moreover, the technique has the unexpected benefit that some of the laser light scatters within the sample, or refracts at the container/sample (e.g., glass/liquid) interface, and travels around the inside perimeter of the container (e.g., if the container is cylindrical). This scattered or refracted light may illuminate bubbles that are located anywhere inside the container, even if those bubbles do not intersect the laser sheet. This phenomenon results from the large difference in refractive index at the surface (which causes substantial reflection and refraction), and may be leveraged to distinguish bubbles from particles (e.g., debris, protein aggregates, etc.) with greater accuracy than other approaches that rely solely on the different morphologies of bubbles and particles. The ability to better discriminate bubbles (which are typically benign) from other particles can be important, as bubbles are typically a significant source of false rejects (e.g., when using conventional image subtraction methods). 
     Other, more complex arrangements may be used to build upon the laser sheet technique. For example, two laser sheets that oppose each other by 180 degrees (both orthogonal to a single camera) may be used, to compensate for the fact that the optical scattering of a laser sheet is different where the laser sheet enters the container as compared to where the laser sheet exits the container. This may reduce the number of required rotations/images by a factor of two. As another example, one or more additional laser sheets may be applied at angles oblique to a first laser sheet, in order to better image particular areas of the container (e.g., a shoulder or stopper area). As yet another example, the imaging system may include a first laser source that generates a laser sheet of one color (e.g., red), and a second laser source that generates a laser sheet of another color (e.g., blue), with some angular offset between the two laser sheets relative to the central axis of the container. Two cameras (each tuned to a different one of the two colors) may then simultaneously capture images. Alternatively, a single camera may be used (e.g., with one or more mirrors, prisms, and/or other optical components) to capture images that preserve the visual information provided by the illumination of each of the differently colored laser sheets (e.g., using a camera that implements a Bayer filter, or using a camera that includes optics and filters to map the different colors of the two laser sheets to different parts of the camera sensor). Whether one or two cameras are used, this approach may reduce the number of required rotations/images by a factor of two (or possibly three, if three differently colored laser sheets are used). As still another example, the imaging system may include a laser source that generates a laser sheet of one color (e.g., red), and an illumination source that generates light of another color (e.g., blue) that illuminates essentially the entire container volume. By using cameras tuned to different colors, it is possible to discriminate between particles inside and outside the container in one plane (within the laser sheet), and simultaneously obtain a snapshot of the entire volume (using the other illumination source). 
     The techniques described above, and elsewhere herein, may provide a number of advantages, such as making possible the automated detection of fibers and other particles in highly viscous products, allowing accurate automated detection of small particles stuck to the inside wall of a container, improving the discrimination of bubbles from particles inside the container, avoiding false detection or other problems arising from small blemishes on the inside wall of the container, reducing the risk of non-compliance due to particles that are not actually inside the container or due to bubbles (i.e., reducing false rejects, which can result in an entire batch of a drug product being discarded), reducing the need for costly manual inspection to avoid false rejects, and/or reducing patient risk. Moreover, it may be possible to implement the techniques by retrofitting current automated inspection equipment with minimal hardware changes (e.g., simply by adding one or more laser sources). 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The skilled artisan will understand that the figures, described herein, are included for purposes of illustration and do not limit the present disclosure. The drawings are not necessarily to scale, and emphasis is instead placed upon illustrating the principles of the present disclosure. It is to be understood that, in some instances, various aspects of the described implementations may be shown exaggerated or enlarged to facilitate an understanding of the described implementations. In the drawings, like reference characters throughout the various drawings generally refer to functionally similar and/or structurally similar components. 
         FIGS.  1  and  2    depict conventional imaging systems for particle detection. 
         FIGS.  3 A and  3 B  depict different perspectives of a first embodiment of an example imaging system operating according to the principles described herein. 
         FIG.  4    depicts an example image of a container illuminated by an imaging system similar to the imaging system of  FIGS.  3 A and  3 B . 
         FIG.  5    depicts a second embodiment of an example imaging system operating according to the principles described herein. 
         FIG.  6    depicts a third embodiment of an example imaging system operating according to the principles described herein. 
         FIG.  7    depicts a fourth embodiment of an example imaging system operating according to the principles described herein. 
         FIG.  8    is a simplified block diagram of an example automated inspection system that may be used with the imaging system of  FIG.  3 ,  5 ,  6  or  7   . 
         FIG.  9    is a flow diagram of an example method for imaging a container containing a sample. 
     
    
    
     DETAILED DESCRIPTION 
     The various concepts introduced above and discussed in greater detail below may be implemented in any of numerous ways, and the described concepts are not limited to any particular manner of implementation. Examples of implementations are provided for illustrative purposes. 
     A first embodiment is shown in  FIGS.  3 A and  3 B , which provide different perspectives of an example imaging system  300 . Specifically,  FIG.  3 A  provides an off-axis perspective view, while  FIG.  3 B  provides a top-down view. In  FIGS.  3 A and  3 B , one or more images of a container  302  (in a holder  303 ) are captured by an imager  304 , while container  302  is being illuminated by a laser source  306 . While container  302  is depicted as a syringe in  FIGS.  3 A and  3 B , it is understood that container  302  may instead be any other suitable type of container, and may have any suitable size and shape. For example, container  302  may instead be a vial, a test tube, a cartridge, and so on. Container  302  may be made of glass, plastic, or any other suitable material (or combination of materials) that is at least partially transparent or translucent so as to allow the passage of light from laser source  306 , and the passage of light to imager  304 . In operation, container  302  may hold a liquid sample. In some use cases, however, container  302  may hold a non-liquid sample, such as a lyophilized or frozen sample. 
     Holder  303  may include any hardware needed to maintain container  302  in a desired position, and to rotate container  302  to allow imager  304  to capture images from other perspectives. Holder  303  may be just one portion of some suitable means for positioning container  302  in one or more desired positions and/or orientations. The positioning means may include any suitable combination of hardware, firmware and/or software, depending on the requirements of imaging system  300 . For example, the positioning means may merely include a platform (e.g., flat base component) from which holder  303  vertically protrudes, either in a fixed orientation or such that holder  303  can be rotated. In other embodiments, however, the positioning means may include automated/robotic hardware (e.g., a robotic arm that includes holder  303  or another suitable holding means such as “fingers” that can grasp/pinch container  302 ). In these latter embodiments, the positioning means may also include a processing unit (e.g., a microprocessor, and/or an application specific integrated circuit (ASIC) or field-programmable gate array (FPGA), etc.), and a memory (e.g., a solid state memory or hard drive memory) storing instructions that the processing unit can execute to grasp/hold/fix, shift, and/or rotate container  302 . Other positioning means are of course also possible. 
     Imager  304  may be a camera including one or more charge-coupled device (CCD) sensors, for example. Alternatively, imager  304  may include one or more complementary metal oxide semiconductor (CMOS) sensors, and/or any other suitable type of imaging device/sensor. Imager  304  may include a telecentric lens, for example, or any other suitable lens (or combination of multiple lenses). In various embodiments, imager  304  may include any suitable combination of hardware and/or software, such as image sensors, optical stabilizers, image buffers, frame buffers, frame grabbers, and so on. More generally, imaging system  300  may include any suitable means for capturing one or more images of container  302  (or another suitable container), with the imaging means including imager  304  and/or any other suitable imaging device or devices (e.g., imager  304  plus one or more mirrors, additional lenses, etc.). 
     Laser source  306  generates a laser sheet  310  that generally conforms to a plane. While laser sheet  310  is referred to herein as a “sheet,” it is understood that real-world limitations on laser source  306 , as well as the media that laser sheet  310  passes through (i.e., air or other gases, the walls of container  302 , and the liquid or other sample within container  302 ), will prevent laser sheet  310  from forming a uniformly flat sheet. For example, laser sheet  310  will experience some diffusion when entering container  302 , and when exiting container  302 . In some embodiments, laser source  306  is a diode laser with 1 to 5 mW power, 30 to 60 degree line fan angle, and 1 to 1.5 mm line width (thickness). In one embodiment, laser source  306  is the Edmund Optics Micro VLM Laser Diode Line part #52-267, with 3.5 mW power, 670 nm wavelength, and 60 degree line fan angle. In another embodiment, laser source  306  is the Edmund Optics Micro VLM Laser Diode Line part #52-268, with 1.6 mW power, 670 nm wavelength, and 30 degree line fan angle. More generally, imaging system  300  may include any suitable means for generating laser sheet  310 , such as laser source  306  or another suitable laser source. In some embodiments (e.g., if container  302  is dark brown in order to block visible light), laser source  306  generates laser sheet  310  using infrared laser light. As the term is used herein, “light” does not necessarily refer to the portion of the electromagnetic spectrum that is visible to humans. 
     As seen in the example embodiment of  FIG.  3 A , laser sheet  310  impinges upon container  302  in a direction  322  that corresponds to (i.e., aligns with) a first axis  330 , and generally conforms to a plane defined by the first axis  330  and a second, orthogonal axis  332 . The second axis  332  is, in the depicted embodiment, parallel to the central axis  320  of container  302 . Moreover, as shown more clearly in  FIG.  3 B , an imaging axis  324  of imager  304  passes through the center of container  302  (i.e., through central axis  320 ), in the depicted embodiment. The imaging axis  324  of imager  304  is substantially parallel to a third axis  334 , where the third axis  334  is orthogonal to both the first axis  330  and second axis  332 . The term “substantially” is used, in this context, to reflect the fact that the alignment of components is never absolutely perfect, and to indicate that small deviations may be acceptable so long as they do not destroy the primary benefits provided by the techniques described herein. For example, in some use cases, imaging axis  324  may be within five degrees of perfect orthogonality to axes  330  and  332 , or within three degrees, within two degrees, within one degrees, etc. 
     Laser sheet  310  has a finite thickness  340  that covers a small range of the third axis  334 . Thickness  340  may represent a 3 times beamwidth of laser sheet  310  along the third axis  334 , for example. Because laser source  306  is not ideal (theoretically perfect), thickness  340  is not precisely uniform at all points along the axis  330 . At least at the locations where laser sheet  310  enters container  302 , however, thickness  340  is substantially less than the diameter of container  302 . Thickness  340  may be set as a design parameter based on both the size (e.g., diameter) of container  302  and the desired (or maximum acceptable, etc.) number of rotations/images. In particular, thickness  340  may be set such that, when container  302  is rotated a certain number of times (to allow imager  304  to capture images from those perspectives), and with a certain angular offset per rotation, all portions of the volume of container  302  (or some large percentage thereof) will eventually become illuminated. This may also require consideration of whether, for any given rotational position of container  302 , laser sheet  310  sufficiently illuminates both sides of container  302  (i.e., both where laser sheet  310  enters container  302 , and where laser sheet exits container  302 ). For example, if container  302  is to be rotated/imaged 90 times for full coverage, and if laser sheet  310  sufficiently illuminates both the entry and exit sides of container  302 , thickness  340  may be set such that laser sheet  310  covers 1/90th (or just over 1/90th) of the circumference of container  302 , with half of that coverage corresponding to where laser sheet  310  enters container  302  and half of that coverage corresponding to where laser sheet  310  exits container  302 . On the other hand, if laser sheet  310  does not sufficiently illuminate the exit side of container  302 , thickness  340  may still be set such that laser sheet  310  covers about 1/90th of the circumference of container  302 , but now with all of that coverage occurring where laser sheet  310  enters container  302 . Thus, for example, thickness  340  may be set to roughly 2 mm if the diameter of container  302  is 100 mm and laser sheet  310  adequately illuminates both container sides: 100 mm*π/(90 rotations)=3.49 mm/rotation of coverage by laser sheet  310  (with half of the coverage occurring on each side of container  302  such that thickness  340  can be 3.49 mm/2=1.74 mm, allowing an extra 0.26 mm of thickness to ensure full coverage). Conversely, thickness  340  may be set to roughly 4 mm (or, alternatively, the number of rotations increased from  90  to  180 ) if laser sheet  310  does not adequately illuminate the exit side of container  302 . 
     While thickness  340  may be constrained on the low end by what is required to give full coverage/illumination, thickness  340  may be constrained on the high end by the need to avoid illuminating too much of the wall of container  302  for any given rotation/image. In particular, the improved discrimination offered by imaging system  300  begins to diminish if laser sheet  310  illuminates any particles that are outside of container  302  but nonetheless appear (from the perspective of imager  304 ) to be between the outermost boundaries of container  302 . In various embodiments, thickness  340  is greater than zero but less than 1 mm, less than 2 mm, less than 3 mm, less than 4 mm, less than 5 mm, etc. Stated as a range, in various embodiments, thickness  340  may be somewhere between 1 and 3 mm, somewhere between 1 and 5 mm, somewhere between 0.5 and 5 mm, etc. 
     In some embodiments, the distance of laser source  306  from container  302 , and the beam angle of laser sheet  310  along the second axis  332 , may be fixed such that laser sheet  310  illuminates an entire cross-section of container  302  in the plane defined by axes  330 ,  332 . In other embodiments, however, laser sheet  310  only illuminates a smaller cross-section of container  302  (e.g., excluding a shoulder or stopper area as shown in  FIG.  3 A , and/or only including an area known to hold a sample, etc.). Moreover, in some embodiments, laser sheet  310  does not fan out at a particular beam angle. For example, laser source  306  may instead generate a more collimated sheet (e.g., a laser sheet covering a substantially fixed/constant range of the second axis  332 ), such as by illuminating a series of cylindrical lenses with a normal Gaussian laser beam. 
     In some embodiments, imaging system  300  is configured differently than shown in  FIGS.  3 A and  3 B . For example, imager  304  may be positioned such that the imaging axis  324  is parallel with (e.g., aligned with) the central axis  320  of container  302 . As another example, the imaging axis  324  of imager  304  may be angled such that it is slightly elevated above, or slightly declined below, the plane defined by the axes  330 ,  334 . As yet another example, the direction  322  of laser sheet  310  may be angled such that it is slightly elevated above, or slightly declined below, the plane defined by the axes  330 ,  334  (e.g., to better illuminate a shoulder or stopper area, etc.). As still another example, imaging system  300  may include one or more additional imagers and/or illumination sources (e.g., as discussed below with reference to  FIGS.  5  through  7   ). 
       FIG.  4    depicts an example image  400  of a container illuminated by an imaging system, such as imaging system  300  of  FIGS.  3 A and  3 B . The imaged container may be container  302  when being illuminated by laser sheet  310 , for example. In particular,  FIG.  4    corresponds to a scenario in which the laser sheet impinges upon the container from the left side of the area depicted in image  400 , and an embodiment in which the laser sheet does not adequately illuminate the exit side of the container (i.e., the right side of the area depicted in image  400 ). 
     Because the thickness of the laser sheet (e.g., thickness  340  of  FIGS.  3 A and  3 B ) only illuminates a small “slice” of the container at any one time/rotation, any particles on the outside of the container (e.g., dust or fibers) are only illuminated (at least, at a level sufficient for clear imaging) along the portion of the container wall that faces the laser sheet source (e.g., where a curving container wall has a surface normal vector that is substantially orthogonal to the imaging axis). Thus, any particles that are on the outside of the container wall will only be visible (or only be clearly visible) when an image shows those particles being unambiguously outside of the container. In the example image  400 , this means that particles on the outside of the container only appear immediately to the left of (and in contact with) the container wall. In embodiments where the laser sheet also adequately illuminates the exit (right) side of the container, the image may also show external particles as being immediately to the right of (and in contact with) the container. Any external particles located on other portions of the container wall, however (i.e., on a part of the wall nearer to the center of image  400 ) would not be illuminated, or at best would be only very faintly illuminated by scattered/refracted light. Accordingly, any particles shown between the left-most and right-most bounds of the container in image  400  would unambiguously be inside the container (i.e., within the portion/slice of the sample illuminated by the laser sheet as it passes through the interior of the container). 
     As seen in  FIG.  4   , the laser sheet illuminates a number of small, dust-like particles on the left side of the exterior of the container, as well as a larger particle (a fiber) just inside the left-side wall of the container. A small particle inside the container is also seen in image  400 , a short distance to the right of the fiber. As used herein, the term “particle” refers to any object that is small relative to the container and solid (e.g., a fiber or other debris, or a protein aggregate, etc.), or possibly a microemulsion, in some use cases. 
     A secondary benefit of imaging with the laser sheet is that bubbles may be illuminated anywhere they are present within the container, even if those bubbles do not intersect the laser sheet. This is caused by the high reflectivity of bubbles, and the fact that some of the laser light scatters and/or refracts at the container/sample interface and/or due to interactions with objects within the sample. One such bubble is depicted in  FIG.  4   . As a result, it may be easier to distinguish bubbles from particles. For example, automated image analysis/processing may initially count an object appearing between the walls of the container as a “candidate” particle, but then decide that the object is a bubble rather than an actual particle if other images, at other rotation points, continue to show the object at positions that would be expected based on the initial object position and the known rotation angle. Conversely, the automated image analysis/processing may identify an object (candidate particle) as an actual particle if the object does not reappear in the corresponding positions of other images at other rotations. 
       FIG.  5    depicts an alternative embodiment in which an imaging system  500  images a container  502  using an imager  504 , a first laser source  506 A and a second laser source  506 B, with laser sources  506 A and  506 B facing in directions that are opposed by 180 degrees. Referring to  FIGS.  3 A and  3 B , container  502  may be similar to container  302 , imager  504  may be similar to imager  304 , and each of laser sources  506 A and  506 B may be similar to laser source  306 , for example. Laser sources  506 A and  506 B generate laser sheets  510 A and  510 B, respectively, each of which may be similar to laser sheet  310  of  FIGS.  3 A and  3 B . In imaging system  500 , however, laser sheet  510 A impinges upon container  502  in a direction  522 A and laser sheet  510 B impinges upon container  502  in the opposite direction  522 B. An imaging axis  524  of imager  504  is substantially orthogonal to directions  522 A and  522 B. 
     By using a second, opposing laser source, imaging system  500  may better illuminate both sides of container  502  (i.e., the “left” and “right” sides, from the perspective of imager  504 ) at each rotation of container  502 , thereby reducing the required amount of rotations and images by half. Or, if the number of rotations/images is not reduced, the second laser source may allow each of laser sheets  510 A and  510 B to have roughly half the thickness (relative to thickness  340  of laser sheet  310 ), which may help ensure that no illuminated particles on the outside of container  502  appear to be just inside the walls of container  502  (e.g., close to, but between, the left- and right-most edges of container  400  in  FIG.  4   ). 
       FIG.  6    depicts another alternative embodiment, in which an imaging system  600  images a container  602  using a first imager  604 A, a second imager  604 B, a first laser source  606 A and a second laser source  606 B. Referring to  FIGS.  3 A and  3 B , container  602  may be similar to container  302 , each of imagers  604 A and  604 B may be similar to imager  304 , and each of laser sources  606 A and  606 B may be similar to laser source  306 , for example. In the embodiment of  FIG.  6   , a laser sheet  610 A generated by laser source  606 A (e.g., similar to laser sheet  310 ) impinges upon container  602  in a first direction  622 A, and a laser sheet  610 B generated by laser source  606 B (e.g., also similar to laser sheet  310 ) impinges upon container  602  in a second direction  622 B that is neither parallel nor orthogonal to the first direction  622 A. For example, there may be a 135 degree angular displacement (or 150 degrees, 120 degrees, 60 degrees, 30 degrees, etc.) between directions  622 A and  622 B. An imaging axis  624 A of imager  604 A is substantially orthogonal to the first direction  622 A, and an imaging axis  624 B of imager  604 B is substantially orthogonal to the second direction  622 B. 
     Laser sources  606 A and  606 B may generate light of different wavelengths/colors. For example, laser sheet  610 A may be red, while laser sheet  610 B may be blue, or green, etc. Moreover, optical filters of imagers  604 A and  604 B may only pass the color of the corresponding laser source (e.g., imager  604 A may be configured to image red light and not blue light, and imager  604 B may be configured to image blue light and not red light). By utilizing different colors, imaging system  600  allows simultaneous imaging by imagers  604 A and  604 B, which may have one or more advantages. For example, imaging two “slices” of the sample at any one time may cut the number of required rotations of container  602  in half relative to the use of a single laser sheet and imager, or allow the thickness of the laser sheets to decrease, as discussed above in connection with  FIG.  5   . 
     In an alternative embodiment, imaging system  600  includes imager  604 A, but imager  604 B is omitted. In such an embodiment, imaging system  600  includes suitable optics (e.g., one or more mirrors, prisms, and/or other optical components) to cause the optical path of imager  604 A to have both a first component aligning with direction  624 A, and a second component aligning with direction  624 B. Imager  604 A may include a Bayer filter (e.g., a common color CCD or CMOS chip), for example, to capture and distinctly preserve the visual information provided by the illumination from each of laser sheets  610 A,  610 B. That is, the single imager  604 A may, for each rotation of container  602 , capture a composite image that includes information sufficient to re-create a first image corresponding to the color of laser sheet  610 A (e.g., red), as well as a second image corresponding to the color of laser sheet  610 B (e.g., green). Alternatively, imager  604 A may include a camera with optics and filters suitable to map the visual information corresponding to the different colors to different parts of the camera sensor. 
       FIG.  7    depicts yet another alternative embodiment, in which an imaging system  700  images a container  702  using a first imager  704 A, a second imager  704 B, a laser source  706  generating a laser sheet  710 , and an additional illumination source  712 . Referring to  FIGS.  3 A and  3 B , container  702  may be similar to container  302 , one or both of imagers  704 A and  704 B may be similar to imager  304 , and laser source  706  may be similar to laser source  306 , for example. Illumination source  712 , however, may not produce a laser sheet, and indeed may not generate a laser at all. For example, illumination source  712  may be include one or more light-emitting diodes (LEDs) and/or another suitable light source that illuminates substantially the entire volume of container  702  at once. Laser sheet  710  (e.g., similar to laser sheet  310 ) impinges upon container  702  in a direction  722 , an imaging axis  724 A of imager  704 A is substantially orthogonal to the direction  722 , and an imaging axis  724 B of imager  704 B is neither parallel nor orthogonal to the direction  722 . While illumination source  712  is shown in a back-lighting arrangement (relative to imager  704 B) in  FIG.  7   , it is understood that, in some embodiments, illumination source  712  may be offset from the imaging axis  724 B. For example, illumination source  712  may include one or more light sources positioned above and/or below the imaging axis  724 B, and angled down and/or up to illuminate container  702  without providing a direct back light. 
     Laser source  706  and illumination source  712  generate light of different wavelengths/colors. For example, laser sheet  710  may be red, and the light produced by illumination source  712  may be blue. Moreover, optical filters of imagers  704 A and  704 B may be configured to pass the color of the corresponding illumination source (e.g., imager  704 A may be configured to image red light but not blue light, and imager  704 B may be configured to image blue light but not red light). By utilizing different colors, imaging system  700  allows simultaneous imaging by imagers  704 A and  704 B, which may have one or more advantages. For example, images generated by imager  704 B may be used to identify particles anywhere in or on container  702  for motion tracking purposes, while images generated by imager  704 A may be used to determine which of those particles are external to container  702 . 
     In an alternative embodiment, imaging system  700  includes imager  704 A but omits imager  704 B. Similar to the arrangement discussed above in connection with  FIG.  6   , for example, imager  704 A may implement a Bayer filter (or optics/filters that map different colors to different areas of the camera sensor), and imaging system  700  may include suitable additional optical components (e.g., mirror(s) and/or prism(s)) to provide imager  704 A with optical path components along both direction  724 A and  724 B. In this manner, imager  704 A may capture images that each preserve the visual information provided by the illumination from laser source  706  and the illumination from light source  712 . 
       FIG.  8    is a simplified block diagram of an example automated inspection system  800  that may be utilized with any one of the imaging systems described above in connection with  FIG.  3 ,  5 ,  6  or  7   . Automated inspection system  800  includes a computer system  802 , which receives images from an imager  804  (e.g., similar to imager  304 ). Imager  804  generates one or more images of a container holding a sample, while the container and sample are illuminated by a laser sheet as described in any of the various embodiments above. 
     Computer system  802  may be a general-purpose computer that is specifically programmed to perform the operations discussed herein, or may be a special-purpose computing device (e.g., a portion of an imaging unit that includes imager  804 ). As seen in  FIG.  8   , computer system  802  includes a processing unit  810  and a memory unit  812 . In some embodiments, however, computer system  802  includes two or more computers that are either co-located or remote from each other. In these distributed embodiments, the operations described herein relating to processing unit  810  and/or memory unit  812  may be divided among multiple processing units and/or memory units, respectively. 
     Processing unit  810  constitutes processing means for analyzing images of containers to detect particles within, and/or on an exterior surface of, those containers. Processing unit  810  includes one or more processors, each of which may be a programmable microprocessor that executes software instructions stored in memory unit  812  to execute some or all of the functions of computer system  802  as described herein. Processing unit  810  may include one or more graphics processing units (GPUs) and/or one or more central processing units (CPUs), for example. Alternatively, or in addition, some of the processors in processing unit  810  may be other types of processors (e.g., ASICs, FPGAs, etc.), and some of the functionality of computer system  802  as described herein may instead be implemented in hardware. Memory unit  812  may include one or more volatile and/or non-volatile memories. Any suitable memory type or types may be included, such as read-only memory (ROM), random access memory (RAM), flash memory, a solid-state drive (SSD), a hard disk drive (HDD), and so on. Collectively, memory unit  812  may store the instructions of one or more software applications, the data received/used by those applications, and the data output/generated by those applications. 
     One such software application stored in memory unit  812  is a particle detection application  814  that, when executed by processing unit  810 , process images generated by imager  804  (and possibly also images generated by one or more other imagers, such as imager  604 B of  FIG.  6  or  704 B  of  FIG.  7   ) to detect particles within the sample (e.g., to determine a particle count within the sample) and/or to determine characteristics of those particles (e.g., particle sizes, types, etc.). Particle detection application  814  may also perform other operations, such as scoring a particular sample based on particle count, sizes, types, and/or other factors in order to determine whether the sample is acceptable or should be discarded. 
     In a relatively simple embodiment, particle detection application  814  may analyze all “slice” images for a particular container/sample (e.g., 90 images corresponding to 90 rotations of the container, with the laser sheet in a fixed orientation), and label anything appearing between the container walls as particles inside the container and anything appearing outside the container walls as particles outside the container. As indicated above, however, more complex algorithms may be used. For example, particle detection application  814  may label anything that appears between the container walls in any image as a “candidate particle,” and then use a classifier (e.g., a trained neural network) to determine whether each candidate is indeed a particle, or instead a bubble (and/or to classify the type of particle, if not a bubble, etc.). As another example, particle detection application  814  may also analyze images from one or more additional imagers (e.g., imager  604 B of  FIG.  6    or imager  704 B of  FIG.  7   ) to more accurately detect, classify, and/or position particles within the container. For example, images from two imagers may be used to better determine three-dimensional particle positions within the container at a single time corresponding to a single rotation/position of the container (which may be needed if the sample is not very high viscosity, and particles/bubbles can move somewhat as the container is rotated from one position to the next). Particle detection application  814  may also, or instead, utilize any other suitable technique(s) to detect, classify, and/or position particles within the container and sample. 
       FIG.  9    is a flow diagram of an example method  900  for imaging a container holding a sample. Method  900  may be performed by one or more portions of imaging system  300 ,  500 ,  600  or  700 , and/or by one or more portions of automated inspection system  800 . For example, block  902  may be performed by one of laser sources  306 ,  506 A,  606 A and  706 , block  904  may be performed by one of imagers  304 ,  504 ,  604 A and  704 A, and block  906  may be performed by computer system  802  (e.g., by processing unit  810  when executing instructions of particle detection application  814  stored in memory unit  812 ). 
     At block  902 , the container is illuminated with a laser sheet that impinges upon the container in a first direction corresponding to a first axis (e.g., direction  322  corresponding/aligning to the first axis  330  in  FIG.  3 A ). A plane of the laser sheet is defined by the first axis and a second, orthogonal axis (e.g., the second axis  332  in  FIG.  3 A ). The laser sheet may pass through a central axis of the container (e.g., the central axis  320  of  FIG.  3 A ), for example. The laser sheet is associated with a certain thickness along a third axis orthogonal to the first and second axes (e.g., the third axis  334  of  FIG.  3 A ). Where the laser sheet enters the container, the thickness of the laser sheet may be greater than zero but less than 1 mm, less than 2 mm, less than 3 mm, less than 4 mm, less than 5 mm, and so on. Stated as a range, in various embodiments, the thickness is somewhere between 1 and 3 mm, somewhere between 1 and 5 mm, somewhere between 0.5 and 10 mm, and so on. In some embodiments, the thickness is between 1/360th and 1/30th of the perimeter (e.g., circumference) of the container. The laser sheet may include white light, or may be constrained to a narrower portion of the visible spectrum (e.g., a red laser sheet), for example. 
     At block  904 , an image of the container, while illuminated by the laser sheet, is captured by an imager (e.g., imager  304 ,  504 ,  604 A or  704 A). The imager has an imaging axis (e.g., imaging axis  324  of  FIG.  3 A ) that is substantially orthogonal to at least the first (and possibly also the second) axis. 
     At block  906 , the image captured at block  904  is analyzed to detect particles within, and/or on an exterior surface of, the container. In some embodiments, external particles are “detected” only for purposes of discounting those particles (e.g., for quality control procedures where particles outside the container may not be of interest). Block  904  may also include classifying the particles that are inside the container (by type, size, etc.), counting particles that are inside the container, and/or one or more other operations. 
     In some embodiments, method  900  includes one or more additional blocks not shown in  FIG.  9   . For example, method  900  may include a first additional block in which the container is moved through a plurality of rotations, about a central axis of the container, while illuminating the container with the laser sheet. Method  900  may also include a second additional block in which a plurality of images of the container are captured by the imager (with each image corresponding to a respective one of the plurality of rotations), and a third additional block in which each of the plurality of images is analyzed to detect particles within, and/or on the exterior surface of, the container. 
     In some embodiments, the laser sheet is a first color (e.g., red), and the imager is configured to filter out colors other than that first color. In one such embodiment, method  900  includes a first additional block in which, simultaneously with illuminating the container with the laser sheet, the container is illuminated with a second laser sheet of a different color (e.g., blue). The second laser sheet may impinge upon the container in a second direction that is not parallel to the first axis (i.e., not parallel to the direction of the other laser sheet), and a plane of the second laser sheet may be defined by that second direction and a third direction substantially parallel to the second axis. Method  900  may also include a second additional block in which an additional image of the container is captured by an additional imager, with the additional imager being configured to filter out colors other than the color of the second laser sheet, and having an imaging axis that is substantially orthogonal to at least the second (and possibly the third) direction. The additional image may be captured simultaneously with the image captured at block  904 , for example. Block  906  may then include analyzing both images of the container to detect the particles. 
     In yet another embodiment, the laser sheet is a first color (e.g., red), and the imager is configured to filter out colors other than that first color, as in the above example. In this embodiment, however, method  900  includes a first additional block in which, simultaneously with illuminating the container with the laser sheet, the container is illuminated with light of a different color (e.g., blue) that illuminates all, or at least a majority, of the volume/contents of the container. Method  900  may also include a second additional block in which an additional image of the container is captured by an additional imager, with the additional imager being configured to filter out colors other than the color of the additional (e.g., non-laser) light source. The additional image may be captured simultaneously with the image captured at block  904 , for example. Block  906  may then include analyzing both images of the container to detect the particles. 
     Although the systems, methods, devices, and components thereof, have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the invention because describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention. 
     Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the scope of the invention, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept.