Automated rapid cytological diagnosis device and staining agent

Abstract

An automated rapid cytology (ROSE) system for smearing, staining, and capturing digital images of biological specimens, such as fine needle aspiration (FNA) specimens, is presented. The system includes a housing with a user interface monitor or screen, a smearing system, a staining system, and an image capture system. The housing may further include a receiver for the biological specimen, capable of directing the specimen to a specimen slide. The smearing system is configured to smear the specimen onto the specimen slide. The staining system is configured to stain the specimen. The image capture system is configured to capture a magnified image of the specimen and store the digital image within the housing or remotely. The digital image may be immediately available for local or off-site review. The latency between staining the specimen and capturing the image may be less than 60 seconds.

Description

[Technical field]

[0001] Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 871,907, filed July 9, 2019, and entitled “AUTOMATED RAPID ON-SITE EVALUATION MACHINE AND STAIN,” which is hereby incorporated by reference in its entirety.

[0002] The present disclosure relates generally to the field of rapid cytology (ROSE). More specifically, some embodiments relate to an automated ROSE device for smearing, staining, and capturing images of biological specimens, such as fine needle aspiration (FNA) specimens, for diagnosis. Summary of the Invention [Means for solving the problem]

[0003] The written disclosure herein describes exemplary embodiments that are non-limiting and non-exhaustive, and reference is made to some of such exemplary embodiments that are depicted in the Figures. [Brief description of the drawings]

[0004] [Figure 1] FIG. 1 is an isometric view of an automated rapid cytology (ROSE) device for smearing, staining, and capturing images of a biological specimen, according to one embodiment of the present disclosure. [Diagram 2] FIG. 2 is a perspective view of the automated ROSE device of FIG. 1. [Diagram 3] Fine needle aspirate (FNA) specimens stained with toluidine, eosin and alcohol (TEA) stain are shown. [Figure 4] FIG. 1 illustrates an isometric view of an automated ROSE device for receiving a biological specimen, according to one embodiment of the present disclosure. [Diagram 5] FIG. 5 shows a perspective view of the automated ROSE device of FIG. 4, equipped with a smear system, a staining system and an image capture system. [Figure 6]FIG. 6 shows a detailed perspective view of the smear system of the automated ROSE device of FIG. 5. [Figure 7] FIG. 6 shows a detailed perspective view of the staining system of the automated ROSE apparatus of FIG. 5. [Figure 8] FIG. 6 shows a detailed diagram of the image capture system of the automated ROSE device of FIG. [Figure 9] A detailed view of the automated ROSE device is shown after smearing, staining and imaging of a biological specimen with the ROSE device. [Figure 10] 2 shows a flow chart of a method or process for using the automated ROSE of FIG. 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0005] Rapid Examination of Cytology (ROSE) is a procedure performed by pathologists and cytotechnologists to confirm the cellularity and adequacy of biological specimens such as fine needle aspiration (FNA) biopsy smears and biopsy impressions. Specimens may be taken from a number of body sites, including lung, thyroid, pancreas, breast sentinel lymph nodes, and skin. ROSE can inform the operator of the adequacy of the cellularity of the specimen and the adequacy of the specimen smear and biopsy impression. If the specimen does not have sufficient cellularity, i.e., the specimen is uninformative, an additional specimen can be taken at the time of the patient appointment, avoiding the need for a follow-up appointment to take a new specimen.

[0006] In some embodiments, ROSE allows for a preliminary diagnosis so that additional specimens can be requested for ancillary testing, such as flow cytometry, microbiological culture, or molecular testing. Although demand for ROSE is high, this service may not be readily available due to various issues such as staffing and resources. ROSE-related services provided by cytotechnologists, residents, or fellows may also not be reimbursed. Time spent on ROSE may therefore represent lost revenue.

[0007] The present disclosure relates to an automated ROSE device for on-site diagnosis of biological specimens, such as FNA specimens. However, the automated ROSE device may also be used to analyze other body fluids, frozen sections, and the like. The automated ROSE device may be used without the assistance of a cytologist, thereby allowing hospitals to meet the demand for ROSE diagnosis. The automated ROSE device may perform smears and stains automatically. Use of the automated ROSE device may result in significant cost savings, as manual microscopic examination is eliminated and digital images of specimen smears may be captured, temporarily or permanently stored, and immediately available for local or off-site review. In further embodiments, the present disclosure also relates to stains that may be used in the automated ROSE device or another diagnostic device.

[0008] The components of the embodiments generally described and illustrated herein could be arranged and designed in a wide variety of different configurations. Thus, the following more detailed description of various embodiments, as illustrated in the figures, is not intended to limit the scope of the disclosure, but is merely representative of various embodiments. While various aspects of the embodiments are presented in drawings, the drawings are not necessarily drawn to scale unless specifically indicated.

[0009] The term "coupled" is broad enough to refer to any suitable connection or other form of interaction (including mechanical and fluid) between two or more entities. Thus, two components may be coupled to one another even if they are not in direct contact with one another. The term "fluid communication" is used in its ordinary sense and is broad enough to refer to an arrangement in which a fluid (e.g., gas or liquid) can flow from one element to another when the elements are in fluid communication with one another.

[0010] FIG. 1 presents an isometric view of the automated ROSE apparatus 100. FIG. 2 shows a perspective view of the automated ROSE apparatus 100. The automated ROSE apparatus 100 may include a housing 102 that may house various components of the automated ROSE apparatus 100. In some embodiments, the ROSE apparatus 100 may include a user interface screen or monitor 110, a slide and / or specimen receiver 120 for receiving biological specimens, a primary motor or track system 130 for transporting or moving specimens within the automated ROSE apparatus 100 and to various systems of the automated ROSE apparatus 100, a slide smearing system 140 for smearing the specimens, a staining system 150 for staining the specimens, and an imaging system 160 for imaging the stained specimens.

[0011] The automated ROSE device 100 can process biological specimens obtained by an operator, smear the specimens, stain the specimens, and capture magnified images of the stained specimens. Figure 3 shows an exemplary image of a stained FNA specimen obtained by the automated ROSE device 100.

[0012] The user interface screen 110 may enable an operator to input patient information, initiate the smearing, staining and / or imaging process, change one or more parameters of the ROSE device 100, etc. For example, the user may control the amount of stain used, the magnification of the image capture, whether to skip certain steps in the process, etc.

[0013] The user interface screen 110 may be an interactive touch screen that may allow an operator to control the automated ROSE apparatus 100. The user interface screen 110 may also display a live image of the stained specimen currently in the automated ROSE apparatus 100. The user interface screen 110 may also display previous images captured by the automated ROSE apparatus 100 that are stored in the memory of the ROSE apparatus 100.

[0014] The slide and / or specimen receiver 120 may be configured to receive a specimen, such as an FNA specimen, from an operator. However, the disclosure is not so limited, and the slide and / or specimen receiver 120 may be configured to receive a variety of different specimens, such as bodily fluids and frozen sections. The slide and / or specimen receiver 120 may include a sample inlet port 121 for inputting a specimen. In other words, the sample inlet port 121 is simply an opening in the housing 102 of the automated ROSE device 100 for inserting a specimen into the automated ROSE device 100. In some embodiments, the slide and / or specimen receiver 120 may include a shelf 122 extending from the inlet port 121. The shelf 122 may be configured to hold a specimen slide 123. It will be understood that various types of slides may be used in accordance with the present disclosure, including, but not limited to, glass slides, polymer slides, and plastic slides. The specimen may be placed on the specimen slide 123 by an operator. The operator may place the specimen in various locations on the specimen slide 123. For example, the operator may load the specimen near the center of the specimen slide 123 or near a lateral edge of the specimen slide 123. The automated ROSE device 100 is configured to draw the specimen into the automated ROSE device 100 for smearing, staining, and imaging the specimen after the operator loads the specimen and activates the automated ROSE device.

[0015] In some embodiments, the automated ROSE apparatus 100 may accommodate multiple slides 123 within the automated ROSE apparatus 100, which may be transported to the shelf 122. First, a specimen is collected from a patient, and then an operator may place a predetermined amount of specimen directly onto the specimen slide 123 on the shelf 122 (which may house or receive slides). The shelf 122 may be flat so that when the specimen is placed onto the specimen slide 123, the specimen does not fall off the specimen slide 123 due to gravity. In some embodiments, the slide and / or specimen receiver 120 does not include a shelf 122, and simply the specimen slide 123 with the specimen is inserted into the entry port 121 of the slide and / or specimen receiver 120.

[0016] The track system 130 of the automated ROSE apparatus 100 is configured to transport the specimen slides 123 having specimens thereon to various locations within the automated ROSE apparatus 100. For example, the track system 130 is configured to transport the specimen slides 123 to the smear system 140, the staining system 150, and the imaging system 160. Other types of transport systems can also be used in addition to or instead of the track system 130.

[0017] In some embodiments, the port 121 of the slide and / or specimen receiver 120 may be a receptacle for receiving a specimen. For example, the port 121 of the slide and / or specimen receiver 120 may simply be an opening into which an operator may insert a specimen. After the specimen is inserted into the port 121, the automated ROSE device 100 may direct the specimen to a specific location to prepare the specimen for smearing, staining, and image capture.

[0018] The track system 130 may include a drive motor 132 configured to transport the specimen slides 123 to various locations within the automated ROSE apparatus 100. In some embodiments, the track system 130 transports the shelf 122 itself within the automated ROSE apparatus 100 to various locations within the automated ROSE apparatus 100. In some embodiments, the track system 130 transports the specimen slides 123 within the automated ROSE apparatus 100 to various locations within the automated ROSE apparatus 100. In other embodiments, the shelf 122 includes a stage that holds the specimen slides 123, and the stage and the specimen slides 123 are transported together within the automated ROSE apparatus 100 to various locations within the automated ROSE apparatus 100.

[0019] In some embodiments, the track system 130 further includes a worm gear 134. The drive motor 132 is configured to rotate the worm gear 134 to transport the specimen slide 123 longitudinally through the automated ROSE apparatus 100. Other mechanical devices can also be used in addition to or in place of the worm gear 134.

[0020] The smearing system 140 may be configured to automatically smear the specimen onto the specimen slide 123. This may be done in a number of different ways. Smearing is the process of spreading the specimen evenly on the specimen slide 123. The smearing system 140 may smear the specimen using a smearing mechanism. The smearing mechanism of the automated ROSE device 100 may smear the specimen using another slide (e.g., a smear slide), thereby creating two slide smears, if desired (one on each slide, i.e., a specimen slide and a smear slide).

[0021] In the illustrated embodiment, the smearing system 140 includes a slide smearing entrance port 141, a slide smearing exit port 142, and a slide storage chamber 143. A slide (not shown) may be inserted into the slide smearing entrance port 141 and then stored in the slide storage chamber 143. The slide storage chamber 143 may be configured to accommodate a plurality of slides (e.g., glass slides, polymer slides, or plastic slides).

[0022] In one embodiment, the specimen may be smeared onto the specimen slide 123 by ejecting or pushing the smear slide from the slide storage chamber 143 near the bottom of the slide storage chamber 143 onto the specimen slide 123 with the specimen. The smear slide may be ejected from the slide storage chamber 143 via a servo motor or other mechanical device. Once the smear slide is on the specimen slide 123 with the specimen, the drive motor 132 may move the specimen slide 123 to release the smear slide used for smearing, and the smear slide may move down the ramp 144 to the slide smear ejection port 142. The smear slide may have enough specimen thereon for additional staining.

[0023] The above example is just one way in which a specimen may be stained. A specimen may be stained in multiple other ways. For example, in one embodiment, a specimen may be placed on the specimen slide 123 at a location near a first edge of the specimen slide 123. After placing the specimen on the specimen slide, a smear slide may be placed on top of the specimen slide 123. The smear slide may be released / dropped from the slide storage chamber 143. The automated ROSE device 100 may then pull the smear slide in a direction toward a second lateral edge (opposite the first lateral edge), optionally at an angle relative to the specimen slide, thereby smearing the specimen. If desired, this method may be used to create two slides (a specimen slide and a smear slide), each with a specimen smear. The smear slide may then be ejected via the slide smear ejection port 142 for later submission to a lab for permanent staining.

[0024] In another embodiment, the specimen may be placed near the center of the specimen slide 123. After placing the specimen on the specimen slide 123, the smear slide may be placed on top of the specimen slide 123 at an angle relative to the specimen slide 123. The smear slide may be released / dropped from the slide storage chamber 143. The smear slide may be rotated in either a clockwise or counterclockwise direction relative to the specimen slide 123. The rotation may be between 15 degrees and 175 degrees. The specimen may be smeared on the specimen slide 123 by rotating the slides relative to each other. In some embodiments, the specimen slide 123 and the smear slide may be rotated relative to each other simultaneously. For example, the specimen slide 123 may be rotated clockwise and the smear slide may be rotated counterclockwise, or vice versa. Once the slides are rotated relative to each other, the smear slide is removed from the specimen slide 123 and ejected via the specimen smear ejection port 142. Once the smear glass slide is removed from the specimen slide 123, the specimen is smeared and ready for staining.

[0025] In another embodiment, the specimen may be placed near a lateral edge of the specimen slide 123. After placing the specimen on the specimen slide 123, the edge of the smear slide may be placed in contact with the specimen at an angle relative to the specimen slide 123. A constant force may then be applied to the specimen by the edge of the smear slide to smear the specimen across the specimen slide 123. The force applied to the specimen may form a substantially constant smear across the specimen slide 123. After the specimen is smeared, the smear slide is removed from the specimen slide 123 and the specimen is ready for staining.

[0026] In some embodiments, the smearing system 140 may include a spreader mechanism (not shown). The spreader is configured to smear a specimen onto the specimen slide 123. The spreader may extend to the height of the specimen slide 123, and the spreader may move laterally relative to the specimen slide 123. Thus, when the track system 130 transports the specimen slide 123 to the smearing system 140, the spreader engages with the upper surface of the specimen slide 123 and moves laterally to smear the specimen disposed on the specimen slide 123. Also, the spreader may be similar to the spreader on the glass slide adapter of U.S. Provisional Patent Application No. 62 / 871,907, filed July 9, 2019, and entitled "AUTOMATED RAPID ON-SITE EVALUATION MACHINE AND STAIN."

[0027] The staining system 150 may be configured to automatically stain the specimen on the specimen slide 123. Staining is the process of applying a stain to the specimen on the specimen slide 123 to facilitate visualization of cellular morphology and structure under a microscope. The automated ROSE device 100 may stain the specimen with one or more histological stains to aid in the diagnostic process. Contemplated stains include TEA stain (described below), methyl green, methylene blue, pyronin G, toluidine blue, acid fuchsin, aniline blue, eosin, orange g, and the like.

[0028] The specimen may be stained in a number of different ways. In some embodiments, the staining system 150 includes a programmable fluid dispensing system. The programmable fluid dispensing system may be pneumatic or non-pneumatic. The fluid dispensing system may be configured to dispense a staining agent onto the specimen smear. The staining solution may include a single staining agent or may include multiple staining agents. Each staining agent may be dispensed onto the specimen smear one at a time, and the staining agents may be configured to diffuse throughout the specimen smear. After a first staining agent is dispensed onto the specimen smear, a second staining agent may optionally be dispensed onto the specimen smear if desired.

[0029] The staining system 150 includes a plurality of stain reservoirs 151, 152, 153, stain dispensers 154, 155, 156, and a tube 157 connecting the stain reservoirs 151, 152, 153 to the dispensers 154, 155, 156. The stain reservoirs 151, 152, 153 may each contain a different stain or may hold the same stain. In some embodiments, one of the stain reservoirs 151, 152, 153 holds water or a cleaning agent for washing off excess stain.

[0030] Stain dispensers 154, 155, 156 deliver precise amounts of stain onto the specimen on specimen slide 123. When multiple stains are used, the stains may be applied sequentially. In some embodiments, the stains may be applied simultaneously.

[0031] Also, various types of stains may be employed by the automated ROSE device 100 disclosed herein. For example, in certain embodiments, commercially available stains such as Diff-Quik stains may be used. Additional stains disclosed herein may also be used. The ROSE device 100 may be adapted for other stains and staining protocols.

[0032] In one embodiment, the present disclosure relates to a stain comprising toluidine and / or eosin. For example, the automated ROSE device 100 may employ a stain comprising toluidine, eosin and alcohol (TEA). The image in FIG. 3 shows an FNA specimen stained with a TEA stain. The TEA stain is cost-effective and can be applied quickly, making it suitable for automated ROSE diagnosis. The TEA formulations disclosed herein may include or may be formulated from a variety of components or ingredients, each of which may impart one or more properties and / or characteristics to the stain formulation. In some embodiments, for example, a TEA stain formulation includes one or more fixative reagents, an acidophilic solution, and a basophilic solution. Additional components (e.g., deionized water, additives, etc.) may also be included in the formulation as needed. The TEA stain may provide excellent image quality staining in 6-10 seconds without the need for air drying.

[0033] In some embodiments, toluidine and eosin may be combined and applied as a single stain, while in other embodiments, individual toluidine and eosin stains may be applied sequentially (e.g., toluidine stain followed by eosin stain or eosin stain followed by toluidine stain).

[0034] In embodiments employing two separate stains (e.g., a toluidine stain and an eosin stain), the first stain stored in the first stain reservoir may include a basophilic solution (e.g., a thiazide dye) and a fixative. For example, in some embodiments, the basophilic solution is toluidine blue and the fixative is an alcohol, such as ethanol. Toluidine blue is a basic thiazine metachromatic dye that has a high affinity for acidic tissue components. Toluidine blue stains nucleic acids blue and polysaccharides purple. Toluidine blue powder can be mixed with ethanol (e.g., 95% ethanol) and water to form this stain. In some embodiments, the amount of toluidine blue ranges from 0.1% to 5% (v / v) in the first stain. In other embodiments, the amount of toluidine blue ranges from 1% to 4% (v / v) or 2% to 3% (v / v) in the first stain.

[0035] The second staining agent stored in the second reservoir includes an acidophilic solution (e.g., a xanthene dye) and a fixative reagent. For example, in some embodiments, the second staining agent includes Eosin Y as the acidophilic solution and alcohol (e.g., ethanol) as the fixative reagent. Eosin Y is a fluorescent acidic compound that combines with basophilic or acidophilic compounds, such as proteins containing amino acid residues such as arginine and lysine, to form salts and stain them dark red or pink as a result of the action of bromine on the fluorescein. In some embodiments, the amount of Eosin Y ranges from 0.5% to 5% (v / v) in the second staining agent. In other embodiments, the amount of Eosin Y ranges from 1% to 4% (v / v) or 2% to 3% (v / v) in the second staining agent.

[0036] As discussed above, the first stain component and the second stain component (e.g., toluidine blue and eosin Y) may be combined or mixed to form a single stain or mixture capable of staining the specimen. In some embodiments, the ratio between the first stain and the second stain may be 50:50. In other embodiments, the ratio between the first stain and the second stain may range from 60:40 to 40:60, 70:30 to 30:70, or 80:20 to 20:80. In still other embodiments, the ratio between the first stain and the second stain may range from 90:10 to 10:90.

[0037] The image capture system 160 may employ a high-resolution camera mounted in the optical path of the microscope / magnifier to capture 2D or 3D images. The wait time to capture an image after staining may be, for example, 120 seconds or less, 100 seconds or less, 80 seconds or less, or 60 seconds or less. The automated ROSE device 100 may include a built-in digital camera and may include magnification options of 1×, 2×, 4×, 10×, 20×, 40×, 60×, or 100×, with or without a ×10 wide-field eyepiece, for a magnification of up to 1000×. Higher magnifications are also within the scope of this disclosure. The automated ROSE device 100 may also include an LED illumination system and a rheostat-based brightness control to match the level of illumination to the object. The focus of the automated ROSE device 100 may be fixed so that the operator of the automated ROSE device 100 does not have to adjust the focus. In some embodiments, the focus may be adjustable by the operator. The digital camera may also be supported by software appropriate for known operating systems.

[0038] Digital images captured by the digital camera may be stored on the automated ROSE device 100 or may be stored at a remote location. The digital images may be immediately available for local or off-site review.

[0039] 4-9 illustrate a process for smearing, staining, and imaging a biological specimen using the automated ROSE apparatus 100. FIG. 4 illustrates the automated ROSE apparatus 100. An operator obtains a biological specimen (such as an FNA specimen) and places the specimen on a specimen slide 123. The operator may label the specimen slide 123 with appropriate patient identification information. The specimen slide 123 may be placed on a shelf 122. After the specimen is placed on the specimen slide 123, a track system 130 transports the specimen slide 123 into the housing 102 of the automated ROSE apparatus 100. The operator may initiate operation of the automated ROSE apparatus 100 by pressing a "start" button on the user interaction screen 110. The specimen slide 123 may be retrieved from the slide storage chamber 143 and transported to the shelf 122 via the track system 130, and the automated ROSE apparatus 100 may be configured to label the specimen slide 123 with appropriate patient identification information.

[0040] 5 shows a perspective view of the automated ROSE apparatus 100. The specimen slide 123 is transported rearwardly by a track system 130 towards a smear system 140. A drive motor 132 drives the movement of the track system 130.

[0041] FIG. 6 shows a perspective view of the automated ROSE device 100 with the specimen slide 123 in the smear system 140. As described above, the smear slide is dropped or released from the slide storage chamber 143. The smear slide is used to smear the specimen placed on the specimen slide 123. This can be achieved by dropping the smear slide onto the specimen slide 123 and then transporting the specimen slide 123 in a forward direction. The shoulder 146 engages the smear slide but allows the specimen slide 123 to pass under the shoulder 146. In this manner, the shoulder 146 pushes the smear slide away from the specimen slide 123, thereby smearing the specimen. After the smear slide is used to smear the specimen placed on the specimen slide 123, the smear slide travels down the ramp 144 and is ejected from the slide smear ejection port 142.

[0042] FIG. 7 shows a perspective view of the automated ROSE device 100 in a staining system 150. The track system 130 can transport the specimen on the specimen slide 123 to the staining system 150. The staining system 150 dispenses a precise amount of staining agent. As described above, one staining agent can be used or two staining agents can be used sequentially. After the staining agent is dispensed onto the specimen, the specimen slide 123 can be tilted and water can be dispensed from a third dispenser connected or coupled to a third staining agent reservoir to remove unwanted excess staining agent. In some embodiments, the specimen slide 123 can be tilted up to 45 degrees. Gravity can allow excess fluid to flow off the specimen slide 123. The excess fluid is then drained into a waste container.

[0043] After dispensing the stain onto the specimen slide 123, a coverslip may be placed onto the specimen slide 123. A pneumatic suction may be configured to pick up the coverslip and place it on the specimen.

[0044] FIG. 8 shows a perspective view of the automated ROSE device 100 in an imaging system 160. A track system 130 may transport a specimen on a specimen slide 123 to the imaging system 160. A high-resolution camera capable of up to 1000× magnification may be used to take live images. These images may be displayed on the user interface screen 110. Images captured by the camera may be available on the network within seconds. The specimen slide 123 may be placed on a stage that may be robotically controlled. In other words, the stage may move the specimen left, right, up, down, etc., to capture a good image of the specimen.

[0045] 9 shows the smear and stained specimen on the specimen slide 123 ejected from the inlet port 121 of the slide and / or specimen receiver 120. The specimen slide can be placed in an alcohol fixative for later processing in the laboratory. The specimen can be restained with standard PAP stain or utilized for molecular testing.

[0046] The automated ROSE device 100 may further include artificial intelligence, such as a machine learning platform. The machine learning platform may be tuned to a number of different stains, such as the TEA stain disclosed above. The machine learning platform may be configured to examine one or more captured images and analyze them for the presence or absence of tumor cells. In some embodiments, the ROSE device 100 may provide a general cytological category (poor, benign, atypical, suspicious for malignancy). In some embodiments, the ROSE device 100 may provide a result where benign or malignant cells are present. In some embodiments, the ROSE device 100 may provide a pathological diagnosis.

[0047] 10 shows a flow chart of a method or process 200 for using the automated ROSE device 100. Step S202 includes introducing a specimen into the automated ROSE device 100. As discussed above, the specimen may be an FNA specimen, a body fluid, a frozen section, etc. The specimen may be introduced directly into the automated ROSE device 100 or the specimen may be placed on a specimen slide, such as specimen slide 123, and introduced via sample inlet port 121.

[0048] Step S204 includes smearing the specimen. As described above, the automated ROSE device 100 may use the smearing system 140 to smear the specimen.

[0049] Step S206 includes staining the smeared specimen with a histological stain. As described above, the specimen may be stained with one or more stains. Contemplated stains include the disclosed TEA stains, methyl green, methylene blue, pyronin G, toluidine blue, acid fuchsin, aniline blue, eosin, orange g, and the like. The specimen may be stained using the staining system 150 described above.

[0050] Step S208 involves capturing an image of the smeared specimen. The image may be captured using a digital camera capable of capturing images using a magnification of up to 1000×.

[0051] Step S210 involves ejecting the smear from the automated ROSE device 100 for possible future analysis. For example, the smear can be placed in an alcohol fixative for later processing in a laboratory. The smear can be restained with a standard PAP stain or utilized for molecular testing.

[0052] Any method disclosed herein includes one or more steps or actions for carrying out the described method. Method steps and / or actions may be interchanged with one another. In other words, unless a specific order of steps or actions is required for proper operation of the embodiment, the order and / or use of specific steps and / or actions may be modified. Furthermore, only subroutines or portions of the methods described herein may be separate methods within the scope of the present disclosure. In other words, some methods may include only some of the steps described in a more detailed method.

[0053] The recitation of a "first" in a claim with respect to a feature or element does not necessarily imply the presence of a second or additional such feature or element. It will be apparent to those skilled in the art that changes may be made to the details of the above-described embodiments without departing from the underlying principles of the disclosure.

[0054] Throughout this specification, a reference to "an embodiment" or "the embodiment" means that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. Thus, the recited phrases or variations thereof found throughout this specification do not necessarily all refer to the same embodiment.

[0055] Similarly, in the description of the above embodiments, it should be understood by those skilled in the art having the benefit of this disclosure that various features may be grouped together in a single embodiment, figure or description thereof for the purpose of streamlining the disclosure. However, this method of disclosure should not be interpreted as reflecting an intention that any claim requires more features than are expressly recited in that claim. Rather, as the following claims reflect, inventive aspects lie in combinations of fewer than all features of any single disclosed embodiment described above. Thus, the claims following this detailed description are expressly incorporated into this detailed description with each claim standing on its own as a separate embodiment. This disclosure includes all permutations of the independent claims and their dependent claims.

Claims

1. An automated rapid cytological diagnosis device, Housing and a smearing system configured to smear a biological specimen onto a specimen slide; a staining system configured to stain the specimen; an image capture system configured to capture a magnified image of the specimen; a transport system for transporting the specimen slide having the specimen thereon to at least one of the smear system, the staining system or the image capture system; a port configured to receive the specimen slide with the specimen disposed thereon; An automated rapid cytology device including:

2. 2. The automated rapid cytology device of claim 1, further comprising a shelf extending from said port for receiving said specimen slide with said specimen disposed thereon.

3. 3. The automated rapid cytological diagnosis device according to claim 1, wherein the waiting time between staining the specimen and capturing the image is less than 60 seconds.

4. 4. The automated rapid cytological diagnosis device according to claim 1, wherein the staining system uses two staining agents.

5. The automated rapid cytological diagnosis device according to any one of claims 1 to 3, wherein the staining system uses a single staining agent or any existing rapid staining agent, including Giemsa staining agent or Toluidine Blue staining agent.

6. The first staining agent is Toluidine blue and Alcohol and The automated rapid cytological diagnosis device according to claim 4, wherein the toluidine blue is in the range of 0.1% to 5%.

7. The automated rapid cytological diagnosis device according to claim 6 , wherein the first staining agent further comprises deionized water.

8. The second staining agent is Eosin Y and Alcohol and The automated rapid cytological diagnosis device according to claim 4, wherein the eosin Y is in the range of 0.5% to 5%.

9. 5. The automated rapid cytological diagnosis device of claim 4, wherein the staining agent comprises a mixture of two solutions mixed together, a first solution comprising toluidine blue and a second solution comprising eosin Y.

10. 10. The automated rapid cytological diagnosis device according to claim 9, wherein a ratio of said mixture, said first solution and said second solution is in a range of 60:40 to 40:

60.

11. The automated rapid cytological diagnosis device according to any one of claims 1 to 10, wherein the housing further includes a user interface screen.

12. The automated rapid cytological diagnosis device according to any one of claims 1 to 11, wherein the smear system includes a slide chamber disposed within the housing, and a plurality of slides are disposed within the chamber.

13. The automated rapid cytological diagnosis device of claim 12, wherein the slide chamber ejects a smear slide from the slide chamber onto the specimen slide having the specimen, and the specimen slide moves relative to the smear slide to smear the specimen onto the specimen slide.

14. The automated rapid cytological diagnosis device according to claim 13, wherein after the specimen is smeared, the smeared slide is discharged through an ejection port.

15. The automated rapid cytological diagnosis device according to any one of claims 1 to 11, wherein the smear system includes placing a cover slip on the specimen slide after staining.

16. The automated rapid cytological diagnosis device according to any one of claims 1 to 15, wherein the staining system includes a plurality of staining agent reservoirs.

17. The automated rapid cytology device of claim 16, wherein the staining system includes a plurality of dispensers, each dispenser being coupled to a corresponding staining agent reservoir.

18. The automated rapid cytological diagnosis device according to claim 16, wherein the staining system tilts the specimen slide to remove excess staining agent on the specimen slide.

19. The automated rapid cytological diagnosis device according to any one of claims 1 to 18, wherein the specimen includes a fine needle aspiration specimen or a biopsy imprint taken from a body part such as the lung, thyroid, pancreas, sentinel lymph node of the breast, or skin.

Images