Patent Publication Number: US-2023160793-A1

Title: Methods and systems for slide processing

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of co-pending U.S. patent application Ser. No. 17/892,493, filed Aug. 22, 2022, which is a continuation application of U.S. patent application Ser. No. 16/240,579, filed Jan. 4, 2019, which is a divisional application of U.S. patent application Ser. No. 15/112,310, filed Jul. 18, 2016, which is the 35 U.S.C. § 371 national stage application of PCT Application No. PCT/US2015/011879, filed Jan. 17, 2015, which claims priority to, and the benefit of, U.S. provisional application entitled “METHODS AND SYSTEMS FOR SLIDE PROCESSING” having Ser. No. 61/928,566, filed Jan. 17, 2014; U.S. provisional application entitled “METHODS AND SYSTEMS FOR SLIDE PROCESSING” having Ser. No. 62/061,015, filed Oct. 7, 2014; and U.S. provisional application entitled “METHODS AND SYSTEMS FOR SLIDE PROCESSING” having Ser. No. 62/089,084, filed Dec. 8, 2014, all of which are hereby incorporated by reference in their entireties. 
    
    
     BACKGROUND 
     Microscope slides are prepared by hand for examination under a microscope. After a sample has been transferred to the slide and dried, the sample can be stained using a pipet or a bath to aid in examination. Such processing can be labor intensive. After drying, the slide is positioned under a microscope for examination and evaluation. In some cases, the processed slide is physically shipped to another facility for examination and evaluation. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views. 
         FIG.  1    is a drawing of an example of a slide processing unit in accordance with various embodiments of the present disclosure. 
         FIG.  2    is a perspective view of an example of the interior of the slide processing unit of  FIG.  1    in accordance with various embodiments of the present disclosure. 
         FIGS.  3 A- 3 D  are perspective views of the interior of the slide processing unit of  FIG.  2    illustrating positioning of a slide in accordance with various embodiments of the present disclosure. 
         FIGS.  4 A- 4 F  are perspective views of an example of a mounting plate and slide clamp that can be used in the slide processing unit of  FIGS.  1  and  2    in accordance with various embodiments of the present disclosure. 
         FIGS.  5 A and  5 B- 5 D  are front and perspective views (respectively) of an example of the interior of the slide processing unit of  FIGS.  1  and  2    in accordance with various embodiments of the present disclosure. 
         FIGS.  6 A and  6 B- 6 C  are front and perspective views (respectively) of an example of the interior of the slide processing unit of  FIGS.  1  and  2    including a slide dispenser unit in accordance with various embodiments of the present disclosure. 
         FIGS.  7 A- 7 H  include various views of an example of a slide dispenser used in the slide processing unit of  FIGS.  1  through  5 D  in accordance with various embodiments of the present disclosure. 
         FIGS.  8 A- 8 D and  8 E- 8 F  are perspective and side views (respectively) of an example of the interior of the slide processing unit of  FIGS.  1  and  2    including a slide treatment system in accordance with various embodiments of the present disclosure. 
         FIGS.  9 A- 9 D  are perspective, side, front and top internal views (respectively) of another slide treatment system of the slide processing unit of  FIGS.  1  and  2    in accordance with various embodiments of the present disclosure. 
         FIG.  10    is a graphical representation of a system for remote access and storage of slide processing using a slide processing unit of  FIGS.  1  and  2    in accordance with various embodiments of the present disclosure. 
         FIG.  11    is a schematic block diagram that illustrates an example of processing circuitry employed in the slide processing unit of  FIGS.  1  and  2    in accordance with various embodiments of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     Disclosed herein are various examples of methods and systems related to microscope slide processing. Reference will now be made in detail to the description of the embodiments as illustrated in the drawings, wherein like reference numbers indicate like parts throughout the several views. 
     Slide processing units can be used for automated processing and imaging samples on a slide. Samples can include fluids (e.g., blood or other bodily fluids), tissue or other types of samples. Once transferred to a slide, the sample can be processed and imaged for examination by a user. Images of the sample can be captured with a camera and displayed and/or stored for examination by the user. The images of the slide can be locally and/or remotely accessed by the user in real time, or can be accessed by the user after capture and storage. For example, images of the processed sample can be stored in memory and subsequently accessed by the user when his or her schedule allows. 
     Referring to  FIG.  1   , shown is a perspective view of an example of a slide processing unit (or slide processor)  100 , in accordance with various embodiments of the present disclosure. The slide processing unit  100  includes a display screen  103  for displaying and/or accessing information about the slide processing unit  100 . For example, the processing status of a slide (e.g., staining, drying, imaging, etc.) can be indicated on the display screen  103 . After the slide has been processed, an image of the sample can be provided through the display screen  103 . In some implementations, the image of the sample can be manipulated through the display screen  103 . The display screen  103  can be touch-sensitive to allow for user input through the display screen  103 . In other embodiments, a user interface unit (e.g., keyboard, mouse, touch pad, etc.) can be communicatively coupled to the slide processing unit  100  through a communications interface. The connection can be through a wireless link (e.g., WiFi, Bluetooth®, Kleer, Infrared, etc.) or through a wired connection. 
     Processing of the slide can be carried out in an enclosed environment to reduce the chance of contamination. A carriage  106  allows a user to insert a slide into the slide processing unit  100  for processing. With the carriage  106  pulled out of the slide processing unit  100 , a slide including a sample can be inserted into the carriage  106 . A guide or slot in the bottom of the carriage  106  can be used to hold the slide in the proper orientation for acquisition by a slide positioner that repositions the slide for processing and imaging within the slide processing unit  100 . 
     Referring next to  FIGS.  2  and  3 A- 3 D , show various perspective views of an example of a portion of the interior of the slide processing unit  100  with the cover including the display screen  103  removed. As shown in  FIG.  2   , the slide processing unit  100  includes a slide positioner  203 , a light source  206 , one or more microscopic lenses  209  and an image capture unit  212 . The structure and operation of the slide positioner  203  is further illustrated in  FIGS.  3 A- 3 D . As seen in  FIG.  3 A , the slide positioner  203  includes a slide clamp  303  that grips the slide  306  when inserted through the carriage  106 . The slide clamp  303  is supported by a mounting plate  309  that can be positioned along the x-axis and y-axis using guide rails and stepper or servo motors with finely pitched jack screws (with a high number of threads per inch). A first pair of guide rails  312  support the mounting plate  309  and allow for its movement along the x-axis. The guide rails  312  are secured in position by end plates  315  that are supported by a second pair of guide rails  318 . The second pair of guide rails  318  allows movement of the first pair of guide rails  312 , and thus the mounting plate  309  and slide clamp  303 , along the y-axis. 
     As can be seen in  FIGS.  3 B and  3 C , a stepper or servo motor  321   a  can be mounted to one of the end plates  315  to control movement along the first pair of guide rails  312 . The treads of the jack screw  324   a  can engage with a threaded portion of a bracket  327   a  (e.g., a threaded sleeve mounted to the bracket or a threaded opening through the bracket) secured to the mounting plate  309  such that rotation of the jack screw  324   a  moves the mounting plate  309  along the first pair of guide rails  312 . Another stepper or servo motor  321   b  can be mounted (e.g., to a support structure) to control movement of the assembly including the slide clamp  303 , mounting plate  309 , first pair of guide rails  312  and end plates  315  along the second pair of guide rails  318  as illustrated in the cutaway view of  FIG.  3 D . The treads of the jack screw  324   b  can engage with a threaded portion of a bracket  327   b  (e.g., a threaded sleeve mounted to the bracket or a threaded opening through the bracket) secured to one of the end plates  315 . Rotation of the jack screw  324   b  moves the assembly along the first pair of guide rails  312 . 
     A low wear, low friction material such as a layer of polymer (e.g., polytetrafluoroethylene (PTFE), fluorinated ethylene propylene, etc.) or other appropriate material can be used to provide for smooth movement of the mounting plate  309  across the first pair of guide rails  312  and/or the end plates  315  across the second pair of guide rails  318 . The position of the slide positioner  203  can be detected using one or more sensors. For example, a sensor  333  (e.g., a capacitive sensor, a magnetic sensor, an infrared sensor, a photosensitive sensor, etc.) can be used to detect the position of an end plate  315  when it reaches a travel limit along the second pair of guide rails  318  as illustrated in  FIG.  3 D . Similar sensors can be used to detect the position of the mounting plate  309  as it reaches a travel limit along the first pair of guide rails  312 . These sensors can also be used as reference points for calibration and/or control of the slide positioner  203 . 
     Referring to  FIGS.  4 A- 4 G , shown are various perspective views of a rotator assembly including the slide clamp  303  and mounting plate  309 . A stepper or servo motor  330  can be mounted to a lower side of the mounting plate  309  as illustrated in  FIGS.  3 A and  3 B . The shaft of the stepper or servo motor  330  can extend through the mounting plate  309 . With the slide clamp  303  secured to the shaft of the motor  330 , the motor  330  can be used to control rotation of the slide clamp  303  about the z-axis defined by the motor shaft. The slide clamp  303  includes an alignment arm  403  on a first side and a clamping arm  406  on a second side. The sample slide  306  can be inserted between the two arms  403  and  406 . The alignment arm  403  is fixed in position to align one side of the slide, while the clamping arm  406  applies pressure to the opposite side the sample slide  306  to hold it in position against the alignment arm  403  during processing by the slide processing unit  100 . A spring can be used to apply a clamping force with the clamping arm  406 . As illustrated in  FIGS.  4 E and  4 F , the clamping arm  406  can include a textured edge  409  that can help grip the slide  306 . In some implementations, the textured edge  409  can be provided by a flexible material (e.g., rubber) that aids in gripping the slide  306 . 
     The mounting plate  309  acts as a stage for microscopic examination of the sample slide  306 . As shown in  FIGS.  4 A- 4 F , the mounting plate  309  includes an opening  412  that allows the light source  206  to illuminate the sample during image capture, when the slide  306  is positioned over the opening  412 . The slide clamp  303  can utilize a spring assembly (e.g., a hold down spring) to apply downward pressure on the slide  306  to hold it against the mounting plate, which acts as a stage during microscopic imaging of the sample. A pressure plate  415  ( FIGS.  4 E and  4 F ) that extends over the alignment arm  403  and clamping arm  406  can be used to secure the hold down spring (or other spring assembly) in position on the slide clamp  303 . A lower edge  418  ( FIG.  4 A ) of the clamping arm  406  and/or the alignment arm  403  can be beveled outward to aid in holding the slide  306  against the surface of the mounting plate  309 . 
     As previously discussed, the stepper or servo motor  330  ( FIGS.  3 A- 3 B ) can be used to control rotation of the slide clamp  303 . The position of the slide clamp  303  can be detected using one or more sensors. In the example of  FIGS.  4 E and  4 F , a sensor  421  is used to detect when the slide clamp  303  has been rotated to a reference position where the slide clamp  303  is aligned to receive a sample side  306  from or return the sample slide  306  to the carriage  106  ( FIG.  1   ). A tab  424  affixed to the slide clamp  303  can be used to detect the position of the slide clamp  303  with the sensor  421  (e.g., a capacitive sensor, a magnetic sensor, an infrared sensor, a photosensitive sensor, etc.). For example, the tab  424  extends from a side of the slide clamp  303  such that it can be detected by the sensor  421  when the slide clamp  303  is oriented with the carriage  106 , where can receive a sample slide  306 . With the reference position known, the stepper or servo motor  330  can be controlled to position the sample slide  306  in the proper orientation for processing and for imaging. 
     For imaging, the sample slide  306  is positioned over the opening  412  of the mounting plate  309 . To ensure that the alignment of the sample slide  306  over the opening  412  is repeatable, the mounting plate  309  can include a guide shoulder  427  opposite from the slide clamp  303  as illustrated in  FIGS.  4 A and  4 B . The guide shoulder  427  can be machined or otherwise formed on the mounting plate  309  so that, as a sample slide  306  is rotated over the opening  412 , the distal end of the slide  306  opposite the slide clamp  303  contacts the guide shoulder  427  to align the position along the longitudinal axis of the slide  306 . The downward pressure applied by the spring assembly of the slide clamp  303  can hold the slide  306  against the mounting plate  309  and prevent the distal end of the slide  306  from moving over the guide shoulder  427 . A slide stop  430  can be used to prevent the distal end of the slide  306  from moving beyond the desired orientation. The slide stop  430  can be machined or otherwise formed on the mounting plate  309  adjacent to the guide shoulder  427 . The combination of the alignment arm  303 , guide shoulder  427  and slide stop  430  allows for consistent positioning of sample slides  306  on the mounting plate  309  during imaging with the microscopic lenses  209  and image capture unit  212  ( FIG.  3 C ). In addition, a sample slide  306  can be reinserted and positioned for reexamination at the same location at different times. The mounting plate  309  can include a backside groove (shoulder or boss) with a clamp stop  433  to provide a hard stop to ensure a 90 degree alignment and prevent over-rotation during positioning of the slide  306  under the digital microscope. Consistency of positioning allows the slide processing unit  100  to relocate image positions on the sample slide  306  after it has been removed and replaced. 
     Referring back to  FIGS.  3 A- 3 D , the movement of a slide  306  by the slide positioner  203  is illustrated. As shown in  FIG.  3 A , the slide positioner  203  includes a slide clamp  303  that grips a sample slide  306  when inserted through the carriage  106 . With the carriage  106  closed, a proximal end of the sample slide  306  extends into the slide processing unit  100 . With the slide clamp  303  rotated to the reference position as detected by sensor  421  ( FIGS.  4 E- 4 F ), the stepper or servo motors  321  can be controlled to align the slide clamp  303  with, but offset from, the proximal end of the sample side  306 . In some embodiments, this can be a default position when no slide  306  is being handled by the slide processing unit  100 . The slide positioner  203  can then be advanced along the y-axis by stepper or servo motor  321   b  to secure the proximal end of the sample slide  306  between the alignment arm  403  and clamping arm  406  of the slide clamp  303 . Pressure from the clamping arm  406  forces the opposite side of the slide  306  against the alignment arm  403 , which properly orients the slide  306  in the slide clamp  303 . 
     The slide clamp  303  can also include a spring assembly for holding the slide  306  in position on the mounting plate. For example, a hold down spring can be configured to apply downward pressure on the top of the slide  306  to avoid twisting of the slide  306  in the slide clamp  303 . In other embodiments, the inner surface of the alignment and clamping arms  403  and  406  can be tapered or beveled outward from top to bottom such that a force is applied to the top edges of the sides of the slide  306  to avoid twisting in the slide clamp  303 . With the slide clamp  303  holding the proximal end of the sample slide  306 , the slide positioner  203  can then be retracted along the y-axis by stepper or servo motor  321   b  to remove the slide  306  from the carriage  106 . With the sample slide  306  clear of the carriage  106 , the slide positioner  203  can reposition the slide  306  along the x-axis and y-axis by moving along the rails  312  and  318 , as well as by rotating the slide  306  about the z-axis. 
     For example, a small drop of blood can be placed on an enumerated location on an unprepared glass microscope slide  306 . The sample slide  306  can then be placed in the carriage  106  ( FIGS.  1 - 2   ) and inserted into the slide processing unit  100 . The slide clamp  303  may then be positioned to grip the proximal end of the slide  306  as illustrated in  FIG.  3 A . The carriage  106  is not shown for illustration. Pressure from the clamping arm  406  forces the slide  306  against the alignment arm  403  as depicted. The slide positioner  203  can then draw the slide  306  out of the carriage  106  and reposition it for processing of the sample. For example, the slide clamp  303  can rotate about 90 degrees for smearing and/or treatment of the blood sample as shown in  FIG.  3 B . 
     In one embodiment, the sample slide  306  is positioned so that a second smearing slide (not shown) drops down to contact the slide at a predefined angle (e.g., about 45 degrees). With the smearing slide resting on the sample slide  306 , the slide processing unit  100  can advance the mounting plate  309  along the first pair of slide rails  312  such that the sample slide  306  moves forward until a short edge of the smearing slide reaches the enumerated location, where it contacts and waits momentarily for capillary action to fully engage the blood droplet along the edge of the smearing slide. In some implementations, the slide processing unit  100  can be configured to optically detect when the sample has reached the smearing slide using one or more sensors and/or light sources. The slide  306  is then backed out from under the smearing slide, allowing capillary action to smear the blood along the length of the slide  306 . In this way, a monolayer of cells can be achieved along at least a portion of the resulting sample smear. The slide  306  with the sample continues to be retracted until the smearing slide drops off the end of the sample slide  306  and falls to the bottom of the slide processing unit  100  where it becomes waste. In some implementations, a drawer in the bottom of the slide processing unit  100  can catch the falling slides so that they can be retrieved by a user for disposal or cleaning and reuse. The mounting plate  309  can again position the slide  306  for further processing of the sample. 
     The slide  306  with the smeared sample can be moved to a desiccation position where it is air or vacuum desiccated for a brief period of time by a small fan in the slide processing unit  100 . Once the smeared sample is desiccated, the slide  306  travels forward as shown in  FIG.  3 B  to be positioned under a slide treatment system containing, e.g., methanol which is sprayed, using micro streams of fluid, over the entire surface of the slide  306 . The position of the slide  306  can be incrementally controlled along the x-axis and y-axis by the stepper or servo motors  321 . This process “fixes” the slide  306 . The slide  306  can then be returned to the desiccation position and the methanol evaporated using forced air. In some embodiments, a vacuum can be used to desiccate the treated sample by drawing air across the slide  306  towards a suction tube located adjacent to the slide  306 . 
     The slide  306  can then be moved forward to one or more treatment positions that each can, in sequence, spray a liquid stain (or other chemical treatment) onto all or a portion of the sample. Various stains or other treatments can be discharged through electronically controlled jet nozzles. Additional rinsing with alcohol and/or other solvents can be accomplished as previously described to provide for Gram staining of slides. A reservoir in the bottom of the slide processing unit  100  can collect any overflow liquid from the slide  306 . A drain connection can allow the overflow liquid to drain from the reservoir into an appropriate disposal system. 
     When the slide preparation is completed, the slide  306  can be moved under a digital microscope as shown in  FIG.  3 C . The digital microscope includes lenses  209  and image capture unit  212 , which includes mirrors, lenses, and/or an imaging device  803  such as, e.g., CCD&#39;s or CMOS circuitry. An image of the sample on the slide  306  can be digitized automatically in a mosaic fashion and stored in memory. The digitized image can be made visible to either the local operator on the display screen  103  (e.g., a self-contained high resolution color monitor) and/or sent via the Internet and/or intranet for review by others skilled in the art of pathology. Focus may be adjusted by adjusting the position of the microscopic lenses  209  over the slide  306 . The light source  206  illuminates the sample during image capture.  FIG.  3 D  illustrates the position of the slide  306  over the light source  206  with the image capture unit  212  removed from view. 
     Referring to  FIGS.  5 A through  5 D , shown are various views of an interior of the slide processing unit  100  that illustrate the orientation of the smearing slide  503  with respect to the sample slide  306 . As can be seen in  FIG.  5 A , the sample slide  306  is positioned so that the smearing slide  503  makes contact at a predefined angle (e.g., about 45 degrees). By allowing the smearing slide  503  to freely move or rock when making contact with the sample slide, the short edge of the smearing slide  503  can rest evenly across the width of the sample slide  306 . With the smearing slide  503  resting on the sample slide  306 , the slide processing unit  100  can advance the mounting plate  309  along the first pair of slide rails  312  such that the sample slide  306  moves forward until a short edge of the smearing slide contacts the blood droplet and allows capillary action to draw it across the edge of the smearing slide  503 . After waiting for a predefined period to allow for the capillary action, the slide processing unit  100  can retract the mounting plate  309  along the first pair of slide rails  312  such that the sample slide  306  moves backward, which smears the blood sample along the length of the sample slide  306 . As the sample slide  306  is retracted from under the smearing slide  503 , the smearing slide  503  can drop to the bottom of the slide processing unit  100  where it can be retrieved from at a later time. For example, a drawer or other access can be included to allow the discarded slides to be retrieved by a user for cleaning and reuse or for appropriate disposal. 
     In other implementations, the smearing slide  503  can be advanced on the sample slide  306  until the short edge reaches the enumerated location and then withdrawn to smear the blood along the length of the slide  306 . In some embodiments, a filament (e.g., a multi-fiber or mono filament) may be used instead of the smearing slide. The filament can extend across the width of, and resting on top of, the slide  306  between two spools (e.g., a dispensing spool and a take-up spool). The slide  306  can be advanced and withdrawn to smear the blood along the length of the slide  306 . After the filament is clear of the slide  306 , the soiled portion of the filament may be wound up on the take-up spool while a clean portion of the filament is uncoiled from the dispensing spool. 
       FIGS.  6 A through  6 D  illustrate an example of a slide dispenser unit  603  that can be used to dispense smearing slides  503  onto the sample slide  306 . In this embodiment, the slide dispenser unit  603  includes a smearing slide magazine  606  configured to hold one or more smearing slides  503  and discharge single smearing slides  503  into a slide sled  609  from an end of the smearing slide magazine  606 . After a sample slide  306  with a sample is received by the slide clamp  303 , the slide positioner  203  can reposition it for smearing of the sample. A smearing slide  503  can be dispensed from the smearing slide magazine  606  by moving down a slide sled  609  and contacting the sample slide  306  at an angle in the range of about 30 degrees to about 60 degrees (e.g., 45 degrees). The smearing slide  503  can be dispensed from the smearing slide magazine  606  using, e.g., a blade that extends to push the smearing slide  503  out of the smearing slide magazine  606  or a wheel that turns to push the smearing slide  503  out of the smearing slide magazine  606 . 
     As the smearing slide  503  leaves the smearing slide magazine  606 , it drops into the slide sled  609  where it slides down until contacting the sample slide  306  located below. A holding bar  612  extending across the distal end of the slide sled  609  holds the smearing slide  503  in the slide sled  609  when the sample slide  306  is moved forward during smearing. The holding bar  612  can include a pivot point that extends toward the bottom of the trough of the slide sled  609  to allow the smearing slide  503  to rock about the center point (side-to-side) when making contact with the sample slide  306 . For example, the holding bar  612  can have a shallow v-shape with the center point providing the pivot point or can include a point or tip that extends downward from the center of the holding bar  612  to provide the pivot point. The pivot point allows the end of smearing slide  503  to self-align with the surface of the sample slide  306 , which aids in the capillary action during smearing. The weight of the smearing slide  503  provides the contact pressure onto the slide  306  with the sample. 
     A hinged joint between the slide magazine  606  and slide sled  609 , which can be controlled using a servo or stepper motor, allows the contact angle to be adjusted. In the example of  FIGS.  6 A- 6 C , the smearing slide  503  contacts the slide  306  with the sample at an angle of about 45 degrees. A capped pin (e.g., a stud, screw, bolt, etc.) can be located at the proximal end of the slide sled  609  such that it extends upward from the bottom of the trough. When the smearing slide  503  is dispensed, it moves over and past the top of the capped pin as it travels down the trough of the slide sled  609 . When the smearing slide  503  reaches the sample slide  306 , the capped pin can press against the opposite end of the smearing slide  503  to restrict movement of the smearing slide  503  back up the slide sled  609  when the sample slide  306  is retracted during smearing. The cap at the top of the capped pin catches the lip of the smearing slide  503  to prevent it from moving back over the top of the capped pin. 
     With the smearing slide  503  in position on the sample slide  306 , the slide positioner  203  can advance the slide  306  until the sample contacts the lower edge of the smearing slide  503  and wait momentarily for the capillary action to fully engage the sample with the lower edge and form a meniscus. The sample slide  306  can then be retracted allowing the capillary action to smear the blood along the length of the slide  306 . The slide  306  with the sample continues to retract until the smearing slide  503  drops off the end of the slide  306  and into the bottom of the slide processing unit  100 . The used smearing slide  503  can be cleaned and sterilized for reuse or can be disposed of appropriately. The slide  306  with the smeared sample can then be moved to a desiccation position where the smeared sample is air desiccated for a brief period of time by a small fan in the slide processing unit  100 . 
     Referring to  FIGS.  7 A through  7 H , shown are various views of another example of a slide dispenser unit  615  that can be utilized in the slide processing unit  100 .  FIGS.  7 A and  7 D  provide front and back views (respectively),  FIGS.  7 B and  7 C  provide left and right side views (respectively),  FIG.  7 E  provides a top view, and  FIGS.  7 F- 7 H  provide various perspective views of the slide dispenser unit. In this embodiment, the slide dispenser unit  615  includes a smearing slide magazine  618  configured to hold one or more smearing slides  503  and discharge single smearing slides  503  into a slide sled  621  from a side of the smearing slide magazine  618 . The smearing slides  503  are held in position by stacking guides  624  that include a gap  627  at the bottom to allow a single smearing slide  503  to be dispensed from the bottom of a stack. 
     After a sample slide  306  with a sample is received by the slide clamp  303 , the slide positioner  203  can reposition it for smearing of the sample. A smearing slide  503  can be dispensed from the smearing slide magazine  618  by a blade  630  that extends to push the smearing slide  503  out of the smearing slide magazine  618  and into the slide sled  621  and then retracts back to allow the next slide in the stack to move into position for dispensing. In the example of  FIGS.  7 A- 7 H , the smearing slide  503  drops into the trough of the slide sled  621  and it guided to the bottom by an end wall  633  and side walls of the slide sled  621 . The bottom of the slide sled  621  is set at a predefined angle (e.g., about 45 degrees) that controls the angle of contact with the sample slide  306 . When the smearing slide  503  reaches the bottom of the trough, the smearing slide  503  moves forward under the bottom of the end wall  633  (as illustrated in  FIGS.  7 A and  7 D ) until it reaches the sample slide  306 . With the smearing slide  503  resting on the bottom of the slide sled  621 , the weight of the smearing slide  503  provides the contact pressure onto the sample slide  306 . The slide sled  621  can be placed approximately the same location as the slide sled  609  shown in  FIGS.  6 A- 6 C . 
     The end wall  633  of the slide sled  621  holds the smearing slide  503  in the slide sled  621  when the sample slide  306  is moved forward during smearing. As seen in  FIG.  7 B , the end wall  633  includes a pivot point  636  that extends toward the centerline of smearing slide  503  to allow the smearing slide  503  to rock about the center point (side-to-side) when making contact with the sample slide  306 . The pivot point  636  allows the end of smearing slide  503  to self-align with the surface of the sample slide  306 , which aids in the capillary action during smearing. A capped pin (e.g., a stud, screw, bolt, etc.) can be located at the upper end of the slide sled  621  such that it extends upward from the bottom of the trough. For example, a small screw or bolt can be secured through a hole or opening  639  in the slide sled  621 . When the smearing slide  503  is dispensed, it moves over and past the top of the capped pin as it travels down the trough of the slide sled  621 . When the smearing slide  503  reaches the sample slide  306 , the capped pin can press against the opposite end of the smearing slide  503  to restrict movement of the smearing slide  503  back up the slide sled  621  when the sample slide  306  is retracted during smearing. The cap at the top of the capped pin catches the lip of the slide  706  to prevent it from moving back over the top of the capped pin. 
     When the smearing slide  503  is ejected, the blade presses against an edge of the bottom slide of a stack of slides in a slide magazine. An electric motor  642  (or solenoid) rotates a lever arm  645  to push the blade forward against a side of the bottom slide. For example, a rod at the end of the lever arm  645  can move inside a channel or groove to translate the rotational motion of the lever arm  645  into linear motion of the blade  630 . Linear motion of the blade  630  can be ensured using guide pins in a groove. The thickness of the blade  630  is less than the thickness of a smearing slide  503  and the height of the gap  627  is more than the thickness of a smearing slide  503 , but less than twice the thickness of the slides, to avoid dispensing more than one slide at a time. 
     The pivot point  636  of the slide sled  621  holds the smearing slide  503  in position while the sample slide  306  is moved forward by the slide clamp  303  until the edge of the smearing slide  503  contacts the sample. At that point, capillary action draws the sample across the edge of the smearing slide  503 . The sample slide  306  can then be retracted while the smearing slide  503  pulls the sample along the surface of the sample slide  306 . The capped pin of the slide sled  621  holds the smearing slide  503  in position while the sample slide  306  is moved back by the slide clamp  303 . As the end of the smearing slide  503  passes over the end of the sample slide  306 , the smearing slide  503  drops out of the slide sled  621  into the bottom of the slide processing unit  100  (e.g., the reservoir or a collection drawer). The slide  306  with the smeared sample can then be moved to a desiccation position where the smeared sample is air or vacuum desiccated for a brief period of time. In some embodiments, a vacuum can be used to desiccate the treated sample by drawing air across the sample slide  306  towards a suction tube located adjacent to the slide  306 . In other implementations, forced air can be blown on the sample slide  306  by a small fan in the slide processing unit  100 . 
     Once desiccated, the sample slide  306  can be positioned under the slide treatment system  703  for staining and/or other chemical treatment of the sample. Referring next to  FIGS.  8 A through  8 F , shown are various views of an example of the slide processing unit  100  including the slide treatment system  703  for staining and/or other chemical treatment of the sample on the slide  306 . The slide treatment system  703  includes one or more jet nozzles  706  for application of a fluid (e.g., stain, water, air, oil or other chemical) to the sample on the slide  306 . The slide treatment system  703  also includes one or more reservoirs  609  for holding the treatment fluids. The fluids can be provided through external supply lines attached to corresponding jet nozzles  706  or from a reservoir  709  that is attached to a jet nozzle  606  through an internal supply line and pressurized using pressure regulated air or other appropriate gas. The slide processing unit  100  can include one or more pressure regulators  712  to ensure that appropriate pressure is applied to the reservoirs  709  for control of the jet sprays. The jet nozzles  706  can be electronically controlled to emit pulsed bursts of fluid fora predefined period of time (e.g.,  20 psec). 
     The jet nozzles  706  can be aligned to focus the fluid spray or micro streams at a known or common location on the surface of the slide  306 . By positioning the jet nozzles  706  at a fixed position above the sample slide  306  and controlling the pressure of the applied fluid, a well-defined application area can be provided.  FIG.  8 A  shows an example of a multi-nozzle arrangement including three jet nozzles  706  that are configured to apply treatment fluids. The jet nozzles  706  can be aligned so that different fluids can be applied to the same location on the sample slide  306  without movement of the slide  306 . For example, four jet nozzles  706  can be arranged and aligned to direct different fluid sprays (e.g., a fixative, a stain, a water wash, and/or an air blast for drying) at a predetermined location. One or more stains and/or fixatives can be stored in individual reservoirs  709 , while the water and air may be supplied from an external source. In other embodiments, some or all of the jet nozzles  706  may be aligned to different locations on the surface of the slide  306 . 
     The fluids may be applied to the sample on the slide using short pulses while the position of the slide  306  is varied by the slide positioner  203  (or slide manipulation mechanism). In this way, various stains or other chemical treatments can be applied to different portions of the smeared sample on the slide  306 . For instance, a stain may be applied to a defined area of the smeared sample after application of a fixative. A water wash may then be applied to remove excess material and a series of air blasts or vacuum applied to dry the sample. Excess fluids can flow off the slide  306  and into a reservoir in the bottom of the slide processing unit  100  for disposal or draining. As shown in  FIGS.  8 B and  8 F , a backsplash  715  can be provided to minimize dispersion of the fluids during treatment of the slide  306 . The slide positioner  203  can position the slide  306  under the jet nozzles  706  and over the backsplash  715  for application of the fluids to the smeared sample. In some implementations, oil may be deposited on the treated sample in order to enhance focusing and imaging. 
     Referring now to  FIGS.  9 A through  9 D , shown in an example of another slide treatment system in accordance with various embodiments of the present disclosure.  FIG.  9 A  shows a perspective view and  FIGS.  9 B- 9 D  show side, front and top internal views (respectively) of the slide processing unit  100 . The slide processing unit  100  includes a slide treatment system having one or more cartridges  718 . The cartridges  718  can hold stains or other chemicals for treatment of the sample on the slide  306 . The stain or other chemical can be applied using deflected micro streams in a manner similar to ink jet printers. By adjusting the position of the sample slide  306  under the nozzles of the cartridges  718 , treatment of the smeared sample can be controlled. 
     When the slide preparation is completed, the slide positioner  203  can retract and rotate the slide  306  under the digital microscope, as illustrated in  FIGS.  3 C and  3 D , utilizing the light source  206 , one or more microscopic lenses  209  and the image capture unit  212  for imaging. As shown in  FIG.  5 A , the light source  206  is positioned below the level of the sample slide  306  for illumination during imaging. Sufficient cooling is included to prevent distortion of the captured images by heat from the light source  206 . A plurality of microscopic lenses  209  can be positioned above the level of the sample slide  306 . One of the lenses  209  can be selected for imaging by the image capture unit  212  and linearly adjusted for focus on the sample. As can be seen in  FIGS.  5 A , two or more microscopic lenses  209  can be mounted on a common baseplate  806 , which is supported by a pair of guide rails  809 . By moving the baseplate  806  along the guide rails  809 , the desired lens magnification can be selected. A motor  812  (or solenoid) can be controlled to shift the baseplate  806  to align the appropriate lens  209  with the image capture unit  212 . As depicted in  FIG.  5 C , linkage  815  can be used to translate the rotational motion of the motor  812  to the linear motion of the baseplate  806 . Sensors and/or mechanical stops can be included to ensure proper alignment of the selected lens with the image capture unit  212 . A dust shield can be provided over the back side of the lenses to avoid accumulation of dust or other dirt on the lenses  209 . 
     With the selected microscopic lens  209  in position, the lens  209  and/or light source  206  can be adjusted for examination and imaging of the sample. For example, the selected lens  209  can be adjusted using a stepper or servo motor  818 . Using appropriate gearing or thread pitch allows for very fine adjustment of the lens  209 , which improves the ability to focus the image for capture. The location of the surface of the sample slide  306  can initially be determined by focusing on an etched portion of the slide  306 . Focus of the microscopic lens  209  can then be automatically carried out by the slide processing unit  100  or manually carried out by the user of the slide processing unit  100 . A hard stop can be provided to prevent the lens  206  from striking the sample slide  306  during adjustment. 
     With the treated sample under the digital microscope, it is possible to automatically identify a monolayer of the smeared sample. As the sample is smeared across the slide  306 , the thickness of the sample on the slide  306  will decrease or be feathered out until the sample smearing is completed. Towards the end of the smearing, there is an area where a monolayer of cells exists (i.e., where the cells are one cell thick, nominally 3-5 microns). In some implementations, the location of the monolayer can be determined by measuring the light passing through the slide. Initially, light can be measured through the glass of the slide  306  on both sides of the sample where no sample exists. This allows the total amount of light coming through clear glass to be determined. The digital microscope can then search for an area where a predefined percentage of the total light is detected passing through the smeared sample. For example, when the light passing through an area of the smeared sample is about 57% of the total light through clear glass, then a monolayer exists in that area. In this way, the location of a monolayer can be determined in the smeared sample. 
     The slide processing unit  100  can be used to automatically acquire images of treated samples and transmit the images for storage and/or evaluation at a remote location. Images of the sample on the slide  306  can be digitized automatically in a mosaic fashion using the image capture unit  212 , which includes mirrors, lenses, and/or the imaging device  803 . The images may be initially acquired at a high resolution and stored in memory in the slide processing unit  100 . The location (or relative position) of each of the mosaic images, the operating conditions of the light source  206 , lens  209  and/or image capture unit  212 , and/or identification of the sample slide  306  can also be stored in memory. In some implementations, the slide processing unit  100  can also send the acquired images for external storage in a local or remote data store. For example, the images can be transmitted to secure data store in the cloud. The slide processing unit  100  can be configured to send the images for external storage at the time of acquisition or store the images in the memory of the slide processing unit  100  at the time of acquisition and send them for external storage at a later time. For example, the images can be transmitted at a scheduled time (e.g., after normal business hours when usage of the network is low) or when the slide processing unit  100  is idle. 
     The digitized images can be made visible to either the local operator on the display screen  103  ( FIG.  1   ) and/or transmitted for review by others skilled in the art of pathology.  FIG.  10    is a graphical representation illustrating a system for remotely accessing and/or controlling the slide processing unit  100 . For example, communication can be established between the slide processing unit  100  and a user device  903  (e.g., a computer, tablet, smart phone, etc.) via a secure network connection over one or more networks  906  (e.g., an intranet, the Internet and/or a cellular network). As discussed, the slide processing unit  100  can store the image data in local memory (or storage) and/or can store the image data in remote storage  909  for later access. The remote storage may be representative of one or more data stores as can be appreciated. 
     In addition, the data can be transmitted to the user device  903  of examination and evaluation. The user device  903  is representative of a plurality of devices that may be coupled to the network  906 . The user device  903  may comprise, for example, a processor-based system such as a computer system. Such a computer system may be embodied in the form of a desktop computer, a laptop computer, personal digital assistants, cellular telephones, smartphones, web pads, tablet computer systems, or other devices with like capability. The user device  903  can include a display such as, for example, a liquid crystal display (LCD) displays, gas plasma-based flat panel displays, organic light emitting diode (OLED) displays, electrophoretic ink (E ink) displays, LCD projectors, or other types of display devices, etc. 
     To improve the data transmission and reduce latency, the resolution of the acquired images can be reduced and compressed prior to transmission to the user device  903 . For example, the resolution of the acquired imaged may be reduced by a predefined amount (e.g., 10 to 1), which does not affect the image quality for review by the user, and sent to the user device  903  using an appropriate compression format (e.g., jpeg). If a higher resolution image is requested by the user during evaluation of the images, then the image processing unit  100  can communicate the higher resolution information to the user device  903  for evaluation. 
     Examination of the sample in the image processing unit  100  can also be actively controlled either locally through the display screen  103  (or other user interface) or remotely via a secure connection with the user device  903 . For example, a pathologist or other user can initially examine the lower resolution images to determine if a condition or problem exists. If there is a question regarding the sample, the higher resolution images can be requested for further examination. In some cases, the higher resolution images of specific areas of the sample can be requested by the pathologist or user to reduce the amount of data being requested. It is also possible for the pathologist or user to actively control the imaging of the sample in real time. This can be especially beneficial if a feature of the sample was captured over multiple images. 
     In some implementations, the pathologist or user can actively control some of the features of the slide processing unit  100  from a remote location. For example, examination of the treated sample can be remotely controlled in real time over the secure connection with the user device  903 . Images can be transmitted to the user device  903  while commands are sent through an interface on the user device  903  to actively control viewing of the images. The commands can allow the pathologist or user to control the examination of the different areas of the stored image data or, with the sample slide  306  in the image processing unit  100 , to control the active imaging of the sample in the image processing unit  100 . Images that have been stored in the remote storage  909  can also be accessed through the user device  903 . 
     In some cases, the user can implement real time control of the slide processing unit  100  with real time images being streamed to the user device  930 . Features such as, but not limited to, control of the iris of the light source  206 , remove switching of microscopic lenses (or objectives)  209 , and control of viewing area can be controlled by a remote operator. Linear adjustment of the lens and/or selection of different lenses can also be controlled remotely. For instance, the pathologist or user can pan between different areas or change the resolution (or magnification) of the image(s) to focus the examination as desired. The pathologist or user can also control the image processing unit  100  while images are being captured of the sample in real time. In this way, the pathologist can examine the sample as if the slide  306  were at his or her location. 
     After imaging and/or examination of the sample is complete, the sample slide  306  can be returned to the carriage  106  by the slide positioner  203 . The user can then remove the sample slide  306  from the slide processing unit  100  for retention or disposal. For example, the user can open the carriage  106  and pull the sample slide  306  out of the grasp of the slide clamp  303 . The processed sample slide  306  can be reinserted into the slide processing unit  100  for subsequent examination using the microscopic lenses  209  and image capture unit  212  ( FIG.  3 C ). The alignment arm  303  of the slide clamp  303  and the guide shoulder  427 , slide stop  430  and clamp stop  433  of the mounting plate  309  ( FIGS.  4 A- 4 F ) allow for consistent positioning of the sample slide  306  during the subsequent imaging. The sample slide  306  can be repositioned by the slide processing unit  100  to return to a location of a previously acquired image for reexamination by a user. In other implementation, the sample slide  306  can be deposited in the bottom of the image processing unit  100  for subsequent removal and disposal. For example, the sample slide  306  may be released and deposited in a receptacle in the bottom of the slide processing unit  100 . 
     Tissue samples may also be processed by the slide processing unit  100  in a similar fashion. Thin slices of tissue may be placed on a slide  306  and introduced to the slide processing unit  100 . As smearing would not be needed, the sample slide  306  would progress through the staining process described earlier (e.g., desiccation and/or chemical treatment) and positioned under the microscope lens  209  for digitization and/or review. In some implementations, a lump section of tissue may be introduced into the slide processing unit  100  in an appropriate sample jar and frozen section preparation may be automatically accomplished. The lump section can be dehydrated by forced air and/or vacuum desiccation with heat. The tissue can then be sectioned using, e.g., a piezo electrically driven knife (or sharp edge) and the resultant thin sections automatically placed on a slide  306 . The sample slide  306  would then progress through the treatment process (e.g., staining) described earlier and positioned under the microscope lens  209  for digitization and/or review. 
     With reference now to  FIG.  11   , shown is a schematic block diagram of an example of processing circuitry that may be used to control the operation of the image processing unit  100  in accordance with various embodiments of the present disclosure. The processing circuitry includes at least one processor circuit, for example, having a processor  1003  and a memory  1006 , both of which are coupled to a local interface  1009 . To this end, the processing circuitry  1000  may be implemented using one or more circuits, one or more microprocessors, microcontrollers, application specific integrated circuits, dedicated hardware, digital signal processors, microcomputers, central processing units, field programmable gate arrays, programmable logic devices, state machines, or any combination thereof. The local interface  1009  may comprise, for example, a data bus with an accompanying address/control bus or other bus structure as can be appreciated. The processing circuitry  1000  can include a display screen  103  for rendering of generated graphics such as, e.g., a user interface and/or receive inputs from a user. 
     The processing circuitry  1000  can also include an input/output interface  1012  through which user input can be received from a user interface unit  1015  such, e.g., a keypad, mouse or touch screen and/or output from the image processing unit  100  can be sent to an external display for rendering. In addition, the processing circuitry  1000  can include one or more communication interfaces  1018  that allow the processing circuitry  1000  to communicatively couple with other communication devices or networks. The communication interfaces may include one or more wireless connection(s) such as, e.g., Bluetooth®, WiFi (e.g., 802.11) or other radio frequency (RF) connection and/or one or more wired connection(s). The processing circuitry  1000  can also include one or more control interface(s)  1021  in communication with motors (e.g., stepper or servo motors  321  and  330 ), solenoids, or other controllable devices used to control operation of the image processing unit  100 . 
     Stored in the memory  1006  are both data and several components that are executable by the processor  1003 . In particular, stored in the memory  1006  and executable by the processor  1003  are IPU (image processing unit) system application(s)  1024 , an operating system  1027 , and/or other applications  1030 . IPU system applications  1024  can include applications that support, e.g., control of the operation of the image processing unit  100 . For example, the IPU system applications  1024  can be configured to automatically process and acquire images of a sample on a slide  306  and provide capabilities for locally and remotely controlling the operation of the image processing unit  100  as has been described. It is understood that there may be other applications that are stored in the memory  1006  and are executable by the processor  1003  as can be appreciated. Where any component discussed herein is implemented in the form of software, any one of a number of programming languages may be employed such as, for example, C, C++, C#, Objective C, Java®, JavaScript®, Perl, PHP, Visual Basic®, Python®, Ruby, Delphi®, Flash®, LabVIEW® or other programming languages. A data store  1033  and other data such as image data captured by the image capture unit  212  can also be stored in the memory  1006 . 
     A number of software components are stored in the memory  1006  and are executable by the processor  1003 . In this respect, the term “executable” means a program file that is in a form that can ultimately be run by the processor  1003 . Examples of executable programs may be, for example, a compiled program that can be translated into machine code in a format that can be loaded into a random access portion of the memory  1006  and run by the processor  1003 , source code that may be expressed in proper format such as object code that is capable of being loaded into a random access portion of the memory  1006  and executed by the processor  1003 , or source code that may be interpreted by another executable program to generate instructions in a random access portion of the memory  1006  to be executed by the processor  1003 , etc. An executable program may be stored in any portion or component of the memory  1006  including, for example, random access memory (RAM), read-only memory (ROM), hard drive, solid-state drive, USB flash drive, memory card, optical disc such as compact disc (CD) or digital versatile disc (DVD), floppy disk, magnetic tape, or other memory components. 
     The memory  1006  is defined herein as including both volatile and nonvolatile memory and data storage components. Volatile components are those that do not retain data values upon loss of power. Nonvolatile components are those that retain data upon a loss of power. Thus, the memory  1006  may comprise, for example, random access memory (RAM), read-only memory (ROM), hard disk drives, solid-state drives, USB flash drives, memory cards accessed via a memory card reader, floppy disks accessed via an associated floppy disk drive, optical discs accessed via an optical disc drive, magnetic tapes accessed via an appropriate tape drive, and/or other memory components, or a combination of any two or more of these memory components. In addition, the RAM may comprise, for example, static random access memory (SRAM), dynamic random access memory (DRAM), or magnetic random access memory (MRAM) and other such devices. The ROM may comprise, for example, a programmable read-only memory (PROM), an erasable programmable read-only memory (EPROM), an electrically erasable programmable read-only memory (EEPROM), or other like memory device. 
     Also, the processor  1003  may represent multiple processors  1003  and the memory  1006  may represent multiple memories  1006  that operate in parallel processing circuits, respectively. In such a case, the local interface  1009  may be an appropriate network that facilitates communication between any two of the multiple processors  1003 , between any processor  1003  and any of the memories  1006 , or between any two of the memories  1006 , etc. The local interface  1009  may comprise additional systems designed to coordinate this communication, including, for example, performing load balancing. The processor  1003  may be of electrical or of some other available construction. 
     Although the IPU system application(s)  1024 , the operating system  1027 , application(s)  1030 , and other various systems described herein may be embodied in software or code executed by general purpose hardware as discussed above, as an alternative the same may also be embodied in dedicated hardware or a combination of software/general purpose hardware and dedicated hardware. If embodied in dedicated hardware, each can be implemented as a circuit or state machine that employs any one of or a combination of a number of technologies. These technologies may include, but are not limited to, discrete logic circuits having logic gates for implementing various logic functions upon an application of one or more data signals, application specific integrated circuits having appropriate logic gates, or other components, etc. Such technologies are generally well known by those skilled in the art and, consequently, are not described in detail herein. 
     Also, any logic or application described herein, including the IPU system application(s)  1024  and/or application(s)  1030 , that comprises software or code can be embodied in any non-transitory computer-readable medium for use by or in connection with an instruction execution system such as, for example, a processor  1003  in a computer system or other system. In this sense, the logic may comprise, for example, statements including instructions and declarations that can be fetched from the computer-readable medium and executed by the instruction execution system. In the context of the present disclosure, a “computer-readable medium” can be any medium that can contain, store, or maintain the logic or application described herein for use by or in connection with the instruction execution system. The computer-readable medium can comprise any one of many physical media such as, for example, magnetic, optical, or semiconductor media. More specific examples of a suitable computer-readable medium would include, but are not limited to, magnetic tapes, magnetic floppy diskettes, magnetic hard drives, memory cards, solid-state drives, USB flash drives, or optical discs. Also, the computer-readable medium may be a random access memory (RAM) including, for example, static random access memory (SRAM) and dynamic random access memory (DRAM), or magnetic random access memory (MRAM). In addition, the computer-readable medium may be a read-only memory (ROM), a programmable read-only memory (PROM), an erasable programmable read-only memory (EPROM), an electrically erasable programmable read-only memory (EEPROM), or other type of memory device. 
     It should be emphasized that the above-described embodiments of the present disclosure are merely possible examples of implementations set forth for a clear understanding of the principles of the disclosure. Many variations and modifications may be made to the above-described embodiment(s) without departing substantially from the spirit and principles of the disclosure. All such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims. 
     It should be noted that ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a concentration range of “about 0.1% to about 5%” should be interpreted to include not only the explicitly recited concentration of about 0.1 wt % to about 5 wt %, but also include individual concentrations (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within the indicated range. The term “about” can include traditional rounding according to significant figures of numerical values. In addition, the phrase “about ‘x’ to ‘y’” includes “about ‘x’ to about ‘y’”.