Abstract:
An automated sample processing system includes a sample input adapted to receive at least one sample container holder manually provided by a user, a consumable input adapted to receive one or more unused consumable supplies manually provided by a user, a waste output adapted to receive used consumable supplies, an automated processing apparatus, and a sample output, wherein the automated processing apparatus includes a decapper adapted to remove a lid from the at least one sample container, at least one agitator adapted to agitate and thereby homogenize the contents of the at least one sample container, a sample collector adapted to remove fluid specimen from the at least one sample container and transfer the specimen to at least one output carrier, and a capper adapted to replace the lid on the at least one sample container.

Description:
RELATED APPLICATION DATA 
       [0001]    This application is a continuation of U.S. patent application Ser. No. 14/068,158, filed Oct. 31, 2013, which is a continuation of U.S. patent application Ser. No. 12/465,032, filed May 13, 2009, now U.S. Pat. No. 8,574,912, which is a continuation of U.S. patent application Ser. No. 10/421,549, filed Apr. 22, 2003, now U.S. Pat. No. 7,579,190, which is a continuation of U.S. patent application Ser. No. 09/521,531, filed Mar. 8, 2000, now U.S. Pat. No. 6,562,299, and Ser. No. 10/421,549 is also a continuation-in-part of U.S. patent application Ser. No. 09/520,421, filed Mar. 8, 2000, now U.S. Pat. No. 6,572,824, the disclosures of which are incorporated by reference into the present application in their entirety. 
     
    
     TECHNICAL FIELD 
       [0002]    The present invention relates to preparation of cytological specimens and, more specifically, to an automated method and apparatus for preparing a plurality of cytological specimens from a common number of patient samples and maintaining one-to-one correlation between the patient samples and the specimens. 
       BACKGROUND 
       [0003]    Cytology is a branch of biology dealing with the study of the formation, structure, and function of cells. As applied in a laboratory setting, cytologists, cytotechnologists, and other medical professionals make medical diagnoses of a patient&#39;s condition based on visual examination of a specimen of the patient&#39;s cells. A typical cytological technique is a “pap smear” test, in which cells are scraped from a woman&#39;s cervix and analyzed in order to detect the presence of abnormal cells, a precursor to the onset of cervical cancer. Cytological techniques are also used to detect abnormal cells and disease in other parts of the human body. 
         [0004]    Cytological techniques are widely employed because collection of cell samples for analysis is generally less invasive than traditional surgical pathological procedures such as biopsies, whereby a tissue specimen is excised from the patient using specialized biopsy needles having spring loaded translatable stylets, fixed cannulae, and the like. Cell samples may be obtained from the patient by a variety of techniques including, for example, by scraping or swabbing an area, or by using a needle to aspirate body fluids from the chest cavity, bladder, spinal canal, or other appropriate area. The cell samples are placed in solution and subsequently collected and transferred to a glass slide for viewing under magnification. Fixative and staining solutions may be applied to the cells on the glass slide for preserving the specimen for archival purposes and for facilitating examination. 
         [0005]    It is generally desirable that the cells on the slide have a proper spatial distribution, so that individual cells can be examined. A single layer of cells is typically preferred. Accordingly, preparing a specimen from a fluid sample containing many cells typically requires that the cells first be separated from each other by mechanical dispersion, fluidic shear, or other techniques so that a thin, monolayer of cells can be collected and deposited on the slide. In this manner, the cytotechnologist can more readily discern abnormal cells. The cells are also able to be counted to ensure that an adequate number of cells have been evaluated. 
         [0006]    Certain methods and apparatus for generating a thin monolayer of cells on a slide advantageous for visual examination are disclosed in U.S. Pat. Nos. 5,143,627, 5,240,606, 5,269,918 and 5,282,978, all of which are assigned to the assignee of the present invention and all of the disclosures of which are incorporated herein by reference in their entirety. 
         [0007]    According to one method disclosed in these patents, a patient&#39;s cells in a preservative fluid in a sample container are dispersed using a spinning sample collector disposed therein. A controlled vacuum is applied to the sample collector to draw the fluid through a screen filter thereof until a desired quantity and spatial distribution of cells is collected against the filter. Thereafter, the sample collector is removed from the sample container and the filter portion impressed against a glass slide to transfer the collected cells to the slide in substantially the same spatial distribution as collected. 
         [0008]    While apparatus manufactured according to the teachings of one or more of these patents have been commercially successful, such as the ThinPrep® 2000 System manufactured and sold by Cytyc Corporation located in Marlborough, Mass., such apparatus requires substantially constant attendance by a trained operator. For example, for each specimen to be prepared, the operator must load the system with an open sample vial containing the patient&#39;s cells in preservative fluid, a sample collector with filter, a glass slide, and an open fixative bath vial containing a fixative solution. The system then cycles automatically, the cells being dispersed by the sample collector, collected against the filter, and transferred to the slide. The slide is then automatically deposited in the fixative bath vial where it must be retrieved by the operator for manual loading in a staining rack for further processing. Thereafter, the sample vial and sample collector must be removed from the system, to avoid inter-sample contamination, before replacements and a new slide are installed to produce another specimen from a different patient&#39;s sample. 
         [0009]    Once a specimen is prepared, fixed, and stained, the specimen may be manually visually inspected by a cytotechnologist, typically under magnification, and with or without various sources of illumination. Alternatively or additionally, automated machine vision systems have been adapted to aid cytological inspection. For example, an automated vision system may perform a preliminary assessment of the entire slide on which the specimen is disposed to alert the cytotechnologist to potentially the most relevant areas of the slide for close inspection, or may be used to rescreen specimens already analyzed by the cytotechnologist. 
       SUMMARY OF THE INVENTION 
       [0010]    While automated specimen preparation systems such as those described hereinabove perform as designed, it is desirable to further reduce manual intervention required of a system operator so as to increase system throughput and operating efficiency. Accordingly, it is desirable to provide the capability wherein a plurality of sample vials, sample collectors with filters, and inspection media such as, for example, glass slides may be loaded in the system. The system then cycles automatically until all of the sample vials are processed and respective specimen slides produced. As a result, after initial loading, the system can operate unattended. 
         [0011]    In one embodiment of the invention, a system includes a sample vial tray for loading of a plurality of closed, capped sample vials. The vials include particles of interest, such as cells, tissue samples, assay product, or other material, typically dispersed in a fluid medium. A sample vial transfer assembly serially retrieves each sample vial, unscrewing a cap thereof, and positioning the now open vial in a position for cooperation with a sample collector and filter, which may be drawn automatically from another tray having a plurality of sample collectors. A sample collector or other mechanism prepares the sample for collection such as, for example, by agitating the sample in a manner so as to create a generally uniform dispersion of particles of interest throughout the sample. Once the particles cells are dispersed, collected against the filter, and transferred to a slide drawn automatically from a slide dispenser having a plurality of clean slides stored therein, the slide is then automatically deposited in a fixative bath vial for a period sufficient to fix the specimen on the slide. Alternatively, the fixative solution may be applied directly to the specimen on the slide by spraying with an air brush or similar technique. In either case, the slide may then be transferred to one of a number of multi-position staining racks previously loaded in the system, so that the fixative solution may dry. Once a first patient&#39;s specimen is prepared, the open sample vial is recapped and replaced in the sample vial tray. The filter of the sample collector may be breached to prevent reuse and resultant inter-sample contamination. The next sample vial can then be retrieved and the specimen preparation method repeated until all of the sample vials are processed. Accordingly, once the system operator loads the sample vial tray, sample collector tray, slide dispenser, and staining racks, and initiates the automatic sequence, the system can operate unattended. 
         [0012]    In order to maintain the integrity of the specimens so produced, it is desirable to maintain one-to-one correlation between the contents of the sample vials and the respective specimens produced therefrom. When a cell sample is collected from a patient and deposited in the preservative fluid in the sample vial, creating cellular particles in a liquid suspension, the vial may be marked with unique identifying indicia corresponding to the type of sample, patient, date obtained, etc. In one embodiment, the identifying indicia may be a bar code label. When the sample vial is loaded into the system and retrieved from the sample vial tray by the sample vial transfer assembly, the indicia corresponding to the sample is identified. In the case of a bar code, a laser bar code scanner can be used. 
         [0013]    Next, an analytical element, such as a microscope slide, is marked with indicia corresponding to the sample indicia. In one embodiment, the analytical element is marked with ink transferred thereto by a printer. The ink may be transferred to multiple overlapping locations, spatially offset from each other on the analytical element, to improve the readability of the element indicia. 
         [0014]    The element indicia are then read automatically by the system. In the case where the element indicia are man-readable alphanumeric characters, an optical character recognition system can be employed in the reading step. Once the system verifies that the element indicia corresponds to the sample indicia, the cells in the sample vial are dispersed, collected, and transferred to the analytical element to produce the specimen. In one embodiment, the system collects a spatial distribution of the cellular particles from the liquid suspension and disposes the collected particles on a stratum of the analytical element or slide. The spatial distribution may be substantially a monolayer of cells collected on a filter or porous membrane of a sample collector. The filter or membrane of the sample collector may be breached mechanically, pneumatically, hydraulically, or otherwise in order to prevent reuse of the sample collector and resultant inter-sample contamination 
         [0015]    An apparatus according to the invention for processing a specimen from a fluid sample may include a processor, an identifier in communication with the processor for identifying indicia corresponding to the sample, a marker in communication with the processor for marking an analytical element with indicia corresponding to the sample indicia, and a reader in communication with the processor for reading the element indicia. Once the processor verifies that the element indicia correspond to the sample indicia, a specimen transferrer in communication with the processor transfers a specimen from the sample to the analytical element. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0016]    The invention, in accordance with preferred and exemplary embodiments, together with further advantages thereof, is more particularly described in the following detailed description taken in conjunction with the accompanying drawings in which: 
           [0017]      FIG. 1  is schematic front view of an automated specimen processing apparatus in accordance with one embodiment of the present invention; 
           [0018]      FIG. 2  is a schematic top plan view of the specimen processing apparatus depicted in  FIG. 1 ; 
           [0019]      FIG. 3  is a schematic front view of an identification correlation subsystem of a specimen processing apparatus in accordance with one embodiment of the present invention; 
           [0020]      FIG. 4  is a schematic top plan view of the identification correlation subsystem of a specimen processing apparatus depicted in  FIG. 3 ; 
           [0021]      FIG. 5  is a schematic perspective view of a capped sample vial in accordance with one embodiment of the present invention; 
           [0022]      FIG. 6  is a schematic perspective view of a sample collector during cell collection in accordance with one embodiment of the present invention; 
           [0023]      FIG. 7A  is a schematic side view of a pre-contact condition of a sample collector approaching a specimen slide; 
           [0024]      FIG. 7B  is a partial schematic cross-sectional view of the apparatus depicted in  FIG. 7A  taken along line  7 B- 7 B. 
           [0025]      FIG. 7C  is a schematic side view of an initial contact condition for a sample collector contacting a specimen slide; 
           [0026]      FIG. 7D  is a schematic side view of a full contact condition of a sample collector contacting a specimen slide; 
           [0027]      FIG. 8  is a schematic perspective view of a rotatable interface for mating with a torque pattern of a sample vial cap; 
           [0028]      FIG. 9A  is a schematic perspective view of a unidirectional interface in a sample vial tray for mating with anti-rotation features of a sample vial body; and 
           [0029]      FIG. 9B  is a schematic perspective view of a bidirectional interface for mating with anti-rotation features of a sample vial body. 
       
    
    
     DESCRIPTION 
       [0030]      FIGS. 1 and 2  are schematic front and top plan views of an automated specimen preparing system  10  for preparing a plurality of specimens from a plurality of fluid samples. The system  10  may be mounted on a wheeled instrument cart  12  for portability. Depicted with an upper cover  14  and front door  16  in open positions, the system  10  includes a specimen preparing apparatus  18  or transferrer, functionally of the type disclosed in the aforementioned patents subject to improvements discussed further herein below. Namely, the specimen preparing apparatus  18  includes subassemblies for automatically dispersing, collecting, and transferring a monolayer of cells to an analytical element, such as a microscope slide. The particular structural details of the specimen preparing apparatus  18 , however, may vary from those disclosed in the aforementioned patents. 
         [0031]    The system  10  includes a first loading station  20  for receiving a plurality of patient samples, each disposed in a sample vial  22 , as best seen in  FIG. 5 . As depicted, the sample vial loading station  20  may have more than one tier to accommodate multiple sample vial trays  24 , two trays  24  being shown. Each tray  24  is removable to facilitate handling and preloading of the vials  22 . In one embodiment, each tray  24  may include locations for forty samples vials  22 , providing a system  10  that can automatically process up to eighty samples without operator intervention. For a system  10  with a process cycle time of about ninety seconds per sample, eighty samples can be processed in about two hours of continuous, unattended operation. 
         [0032]    The system  10  also includes a second loading station  26  for receiving a plurality of sample collectors  28  disposed in a sample collector tray  30 . As best seen in  FIG. 6 , each sample collector  28  has a porous membrane or filter  29  at one end thereof against which cells are collected. The sample collector loading station  26  may have more than one tier to accommodate multiple sample collector trays  30 , two trays  30  being shown. Each tray  30  is removable to facilitate handling and preloading of the sample collectors  28 . In one embodiment, each tray  20  may include locations for one hundred sample collectors  28 , providing a system  10  which can automatically process the eighty samples without operator intervention. The collectors  28  may also be provided to the operator preloaded in the collector tray  30 , which may be reusable or discardable, as desired. Both loading stations  20 ,  26  include elevators for raising and lowering the trays  24 ,  20 , as required, so that sample vial and collector transfer assemblies can access, respectively, each of the sample vials  22  and collectors  28 . 
         [0033]    Blank glass microscope slides are preloaded in two removable cartridges  32 , each with the capacity to hold one hundred slides. Two cartridges  32  are provided to ensure that there are a sufficient number of slides available in the system  10  to process the maximum number of sample vials  22 . While glass microscope slides are typically used for preparing cytological specimens, other analytical elements, such as natural or synthetic material assay strips and the like, are suitable for other analyses and testing, as known by those skilled in the art, and could be employed in the system  10  with suitable handling equipment. 
         [0034]    One or more staining racks  34  may be provided in an unloading area  36  of the system  10  to receive the slides once the cytological specimens have been transferred thereto. In the depicted embodiment, four staining racks  34  are provided, each with a capacity of twenty slides. Accordingly, eighty sample vials  22  can be processed without having to remove the staining racks  34 . Staining rack adaptors may be provided so that the staining racks  34  can be loaded into automated, commercially available cytological specimen stainers after removal from the system  10 . Accordingly, prepared specimens can be efficiently and rapidly unloaded from the system  10  and the specimens stained with minimal manual intervention. 
         [0035]    Once a specimen has been transferred to a slide and before the slide is disposed in the staining rack  34 , a fixative solution may be applied to the specimen at a coating station  38 . The coating station  38  includes a fixative reservoir  40  which holds the solution used to fix or preserve the specimen on the slide after preparation by the system  10 . In one embodiment, the reservoir has sufficient capacity to allow at least a day and preferably a week of average usage without the need for refilling or replacement. The fixative may be applied to the specimen by an air brush technique in which the fixative solution is gently sprayed on the specimen so as not to disturb the spatial distribution of the cells on the slide. 
         [0036]    More specifically, in one embodiment, an airbrush having a generally conical spray distribution pattern may be used to apply a substantially uniformly dense layer of fixative solution to a generally circular cell transfer area on the slide. A fine mist may be applied in one or more short duration bursts to prevent displacing a monolayer of cells on the slide, typically using a very small volume of fluid dispensed from the airbrush using very low differential air pressure. For example, each burst may apply about 20.+−0.2.mu·l of fixative solution over a period of about 0.6 seconds. A slight positive pressure may be maintained in the reservoir  40  to compensate for any pressure head, thereby maintaining control of the dispensed volume per burst. The airbrush may be of any conventional design capable of handling the small volumes applied and capable of providing the desired uniform conical spray distribution pattern. In general, primarily an airbrush nozzle, needle valve, and body are employed, with flow being controlled by an external valve, rather than a trigger valve typically supplied with the airbrush. The pressure source applied to the airbrush may be calibrated and maintained at a fixed pressure in order to ensure a predetermined fixative flow rate for a particular airbrush, thereby achieving the desired dispensed volume per burst. 
         [0037]    During preparation of each specimen, a small volume of preservative fluid from the sample vial  22  is drawn through the collector membrane  29 . A waste bottle  42  is provided in fluidic communication with the specimen preparing apparatus  18  so that waste fluid can be drained during specimen preparation. The waste bottle  42  may be mounted to an interior of the front door  16  to facilitate removal and replacement of the bottle  42  for emptying. 
         [0038]    A waste bin  44  may also be provided to catch used sample collectors  28 . Prior to being discarded, the porous membrane or filter  29  of each collector  28  may be breached so that the collector  28  cannot be reused and possibly contaminate another specimen. The membrane  29  may be breached by any of a variety of methods. For example, the collector  28  may be overpressurized, pneumatically with air or hydraulically with fluid, so as to burst the membrane. Alternatively, the membrane  29  can be mechanically ruptured, for example, by impressing the membrane  29  on a sharp object, such as a pointed protrusion or knife edge mounted in the system  10 . For preparing cytological specimens, the membrane may have a pore size on the order of about ten microns or less. 
         [0039]    A computer controller or processor  46  is provided to communicate with and coordinate operation of the various sensors and components of the system  10  to permit automatic, unattended operation during specimen preparation. The processor  46  includes an appropriate operator interface  47  with associated input keypad or buttons and an output display, such as a liquid crystal diode display. Instructions, prompts, and error messages may be in text, error code, or symbol formats. Text displays may be in a variety of operator selectable languages, such as English, French, German, Italian, Japanese, and Spanish. Audible outputs corresponding to operator prompts, error conditions, keypad inputs, and completion of automatic processing may be provided. A thermal paper printer  48  or other type of printer may be provided, as well, to generate a permanent paper record of system operation and sample processing. For example, for each batch of eighty or fewer sample vials  22  processed, the printer  48  may generate a report containing the date and time processing began, a listing of the sample vials  22  not successfully processed (including error type and tray location), and a listing of the sample vials  22  successfully processed (including sample identification information and tray location). 
         [0040]    In order that the system  10  maintains correlation between each sample vial  22  and a respective specimen prepared therefrom, an identification correlation subsystem  50  is provided, as depicted schematically in front and top plan views in  FIGS. 3 and 4 , respectively. In accordance with one embodiment of the present invention, in order to prepare a specimen from a sample vial  22 , a selected capped vial  22   a  is removed from one of the sample vial trays  24  by a sample vial transfer assembly  52 . The vial transfer assembly  52  includes a four-fingered gripper  54  configured to reliably and repeatable grasp a cap  56  of the vial  22   a . The vial transfer assembly  52  is movable about a plane above the vial tray  24 , left to right and into and out of the drawing as depicted in  FIG. 3 , so that the gripper  54  can be aligned above any of the forty vials  22  loaded in the tray  24 . Once aligned with a desired vial  22   a , the tray  24  is raised by the tray elevator, the vial cap  56  grasped by the gripper  54  and tightened as will be discussed in greater detail herein below, and the tray  24  lowered. In order to access vials  22  on the other tray  24 , the vial transfer assembly  52  can be retracted to one side, outside a footprint of the trays  24  and the tray elevator operated to raise or lower the tray  24 , as necessary. Similar handling is provided for the sample collectors  28  and collector trays  30 . 
         [0041]    Each vial  22  includes identifying indicia, such as a bar code label  58  mounted thereon, which corresponds to and uniquely identifies the vial  22  and the sample contained therein. The selected vial  22   a  is then presented by the vial transfer assembly  52  to an identifier, such as a laser scanner bar code reader  60 , so that the particular vial  22   a  can be identified. Because the circumferential orientation of the vials  22  in each tray  24  and that of the respective bar code labels  58  can vary, upon presentation to the bar code reader  60 , the vial transfer assembly  52  rotates the sample vial  22   a  about a vertical axis passing generally through an axial centerline thereof, as best seen in  FIG. 4 , to present the label  58  to the reader  60 . 
         [0042]    Once the bar code label  58  or other identifying indicia has been identified and communicated to the processor  46 , the processor  46  directs the preparation of an analytical element, such as a microscope slide  62 , for receipt of a specimen from the selected vial  22   a.    
         [0043]    Referring to  FIG. 4 , a slide carriage  64 , translatable along a carriage rail  66 , first extracts a slide  62  from one of the slide cartridges  32 . Each slide  62  has tightly toleranced dimensions and chamfered edges to facilitate handling and transfer of the slide  62  by the components of the system  10  and minimize the likelihood of mishandling or jamming. In one embodiment, the slide  62  is manufactured from glass and has a width of about one inch, a length of about three inches, and a thickness of about 0.04 inches. One end  68  of the slide  62  is frosted or coated to facilitate marking, as will be discussed in greater detail herein below. The frosted end  68  may have an area of about one square inch. A frosted annulus  70 , defining an area to where the cells are transferred, may also be provided to facilitate manual or automatic scanning of sparse specimens. The bounded specimen area may have an area of about one square inch, substantially equivalent to the surface area of the membrane  29 . Additionally, one corner  72  of the frosted end  68  of each slide  62  may be chamfered to a greater degree than the other corners to ensure proper orientation of the slide  62  in the slide cartridge  32  and proper presentation of the slide  62  to downstream components. 
         [0044]    Once the bar code label  58  on the sample vial  22   a  has been identified and before the sample vial  22   a  is uncapped and a specimen produced therefrom, the slide carriage  64  conveys the slide  62  to a marker in communication with the processor  46  for marking the slide  62  with indicia corresponding to the sample indicia on the bar code label  58 . In one embodiment, the marker may be a printer  74 , such as an ink jet printer, thermal printer, laser printer, or other suitable marker capable of producing substantially permanent indicia on the slide  62 . In the depicted embodiment, the printer  74  is a dot matrix impact printer utilizing a multi-pin impact head  76  and replaceable ribbon cartridge  78 , which feeds an ink ribbon  80  to a zone between the impact head  76  and the slide  62 . 
         [0045]    The processor  46  next directs the printer  74  to mark the slide  62 . The slide indicia may have any of a variety of forms including one or more alphanumeric characters, as shown generally at  82 . It is generally desirable to mark the slides  62  with man-readable indicia so that the cytologist examining a fixed, stained specimen can readily identify the specimen and associated sample from which the specimen was prepared. Further, specimens are often archived and retained for extended periods. Accordingly, it is generally desirable to avoid using an indicia standard that may fall into disuse or become obsolete. While the slide indicia may be marked on an adhesive label bonded to the slide  62 , subsequent processing such as fixing and staining may degrade the indicia or bond. Because specimen slides  62  are often archived in slide file drawers, it is generally desirable that the slide indicia  82  be oriented along the width or narrow dimension of the frosted end  68  so as to be readable without requiring removal of the slide  62  from the file drawer. 
         [0046]    The slide indicia printing method and printing media should be resistant to the solvents used in the specimen preparing, fixing, and staining processes. Typical solvents include ethanol, methanol, xylene, water, and a clarifier solution consisting of 0.025% glacial acetic acid in distilled water. In general, commercially available carbon black based printing ink ribbons  80  have been found to perform well when printing on frosted ends  68  produced by coating the ends of the slides  62  with a white epoxy paint material. 
         [0047]    In order to generate readily discernible characters  82  using a low cost printer  74 , the processor  46  may control operation of the printer  74  and the slide carriage  64  so as to first transfer a spot of ink to a first location on the slide  62  and then transfer another spot of ink to a second location offset spatially and slightly overlapping the first location. By double-striking, or alternatively striking a third or more times in different offset directions to blend the ink spots in a particular region of the character, a relatively low cost nine pin dot matrix printer can produce alphanumeric characters substantially visually consistent with those produced by a much more expensive dot matrix printer having many more pins in the impact head. 
         [0048]    Once the slide  62  is marked, the processor  46  directs the slide carriage  64  to advance the slide  62  along the carriage rail  66  to a reader in communication with the processor  46  for reading the slide indicia  82 . In the case where the specimen indicia is composed of alphanumeric characters, the reader may be an optical character recognition (OCR) scanner  84  or system. In one embodiment, a total of four strikes are employed per pin using a nine pin printer in order to meet OCR font specifications typical for higher resolution dot matrix printers. 
         [0049]    The processor  46  verifies both that the slide indicia  82  is readable by the OCR scanner  84  and that the slide indicia  82  corresponds to the sample indicia identified from the bar code label  58  on the selected vial  22   a . In the event the slide indicia  82  cannot be read or the slide indicia  82  does not correspond to the sample indicia, the slide  62  may be removed automatically from the slide carriage  64  using an ejector or other apparatus, as discussed in greater detail hereinbelow, and discarded in the waste bin  44  or other waste receiving area. If multiple slides  62  fail in succession or if more than a predetermined number of slides fail during processing of a batch of sample vials  22 , the system  10  may be programmed optionally to halt automatic operation and alert the operator with a suitable error message. 
         [0050]    Upon verification of both criteria, the sample vial transfer assembly  52  removes the cap  56  from the sample vial  22   a  so that the specimen preparing apparatus  18  can cycle. A sample collector  28  is taken automatically from the collector tray  30  at the second loading station  26  and inserted into the specimen preparing apparatus  18 . Thereafter, the membrane  29  of the collector  28  is inserted into the specimen vial  22   a  to a predetermined depth as shown in  FIG. 6  and, in one embodiment, the collector  28  is rotated to disperse the cells in the preservative fluid. A vacuum system  88  applies a controlled pressure and vacuum cycle to the collector  28  so that cells are collected in a monolayer against the membrane  29 . The cells are subsequently transferred to the zone within the frosted annulus  70  on the slide  62  as shown schematically in  FIGS. 7A-C . According to another embodiment, the sample vial  22  may be rotated prior to uncapping to disperse the cells in the preservative solution, as will be discussed in greater detail hereinbelow. 
         [0051]    In order to provide for transfer of the collected cells to the slide  62  without disturbing the spatial distribution thereof, it is desirable that the membrane  29  of the collector  28  first contact the slide  62  generally at a single location, forming a predetermined small pre-contact angle between the substantially planar membrane  29  and a deposition surface of the slide  62 , and then gently and gradually enter into complete contact with the slide  62 . 
         [0052]    As depicted in  FIG. 7A , after collecting the cells on the membrane  29 , the specimen preparing apparatus  18  inverts the collector  28  to drain any excess fluid therein into the waste bottle  42  mounted on the cart door  16 . The apparatus  18  slowly elevates the membrane  29  to a position proximate the slide  62 , which is retained in an inverted orientation in a slide holder  90  hanging from two studs  92  captured by the slide carriage  64 . Insofar as the studs  92  are of different lengths, the holder  90  and the slide  62  are positioned in an orientation which is slightly offset from horizontal. 
         [0053]      FIG. 7B  is a partial schematic cross-sectional view of the specimen preparing apparatus  18  and slide holder  90  depicted in  FIG. 7A , taken along line  7 B- 7 B. Viewed in conjunction with  FIG. 7A , as the apparatus  18  continues to elevate the collector  28 , two pre-adjusted jack screws  94  first contact the slide holder  90  at one end thereof. As the apparatus  18  elevates the collector  28  further, the holder  90  achieves a more horizontal orientation due to contact with the jack screws  94  until an edge of the membrane  29 , shown generally at  29   a  in  FIG. 7C , contacts the slide  62 . At this point in the cycle, the angle formed between the membrane  29  and the slide  62  may be on the order of several degrees or less, typically 0.75.+−.0.25 degrees. 
         [0054]    As the apparatus  18  is raised further to an end-of-travel position, as depicted in  FIG. 7D , substantially full planar contact results between the membrane  29  and the slide  62 , as the slide holder  90  is effectively fully supported by the membrane end of the collector  28 . Note the clearance between the jack screws  94  and the holder  90  at the end-of-travel position. Accordingly, by initially providing a two point contact between the jack screws  94  and slide holder  90 , the holder  90  and, as a result, the slide  62  mounted thereon, can be oriented in such a manner as to be nearly parallel to the collector membrane  29  when the membrane edge  29   a  first touches the slide.  62 . As the apparatus  18  moves to the end-of-travel position, the slight rotation of the holder  90  through about one degree or so conforms the membrane  29  to the surface of the slide  62 , gently displacing any excess liquid from the surface of the membrane and substantially preventing the capture of air bubbles between the membrane  29  and the slide  62  without disturbing the spatial distribution of the cells. With intimate contact now achieved between the membrane  29  and the slide  62 , the cells captured therebetween can be readily transferred, for example with minimal positive pressurization of the collector  28  which slightly bows the membrane into a convex configuration. 
         [0055]    As the membrane  29  is thereafter withdrawn from the surface of the slide  62 , the reverse procedure takes place, leaving the transferred cells on the slide  62  in a undisturbed monolayer, substantially similar to the spatial distribution created when initially collected against the membrane  29 . By providing clearance between the studs  92  and the slide holder  92  which affords a limited vertical range of motion of the slide holder  90 , monolayers of cells can be reliable and repeatably transferred to slides  62  from a plurality of patient samples. Additionally, because the slide holder  90  is effectively floating at the time of cell transfer on a fluid bearing created at the interface of the membrane  29  and the slide  62 , variability in slide thickness, membrane location, and slide/membrane parallelism are readily accommodated. Accordingly, there is no requirement for time consuming, precision setup of the apparatus  18  and slide holder  90  to ensure proper cell transfer. 
         [0056]    After transferring the cells to the slide  62 , a fixative solution may then be applied to the transferred specimen and the slide  62  transferred from the slide carriage  64  to one of the staining racks  34  at the unloading area  36  using a slide transfer assembly such as a translating slide ejector  86 . The slide ejector  86  and/or the unloading area  36  may include automatic height and side-to-side translation capability, so as to be able to accept the prepared specimen slide  62  in a next open slot in any one of the plurality of staining racks  34 . 
         [0057]    After preparation of the specimen, the membrane  29  of the used collector  28  is breached and the collector  28  discarded in the waste bin  44 . The cap  56  is replaced on the sample vial  22   a  and the vial  22   a  returned to its location in the vial tray  24 . If there exist additional sample vials  22  which have not yet been processed, a next vial  22  is removed automatically, the sample indicia identified, and a next specimen prepared therefrom according to the steps described hereinabove. 
         [0058]    In order that the system can process automatically the specimens from fluid samples in the sample vials  22 , each vial  22  and cap  56  includes one or more structural features which facilitate grasping of the closed, capped vial  22  by the sample vial transfer assembly  52 , as well as removal and reinstallation of the cap  56 . In one embodiment depicted in  FIG. 5 , the sample vial  22  includes a body  23  having a generally cylindrical outer surface, an open end, a closed end, and at least one lug  25  disposed about the outer surface. The lug  25  performs an anti-rotation function, preventing the body  23  from rotating when disposed against adjacent structure. The sample vial cap  56  is releasably engagable with the body  23 , the cap  56  including an outer surface with a torque pattern  27  thereon for mating with a rotatable interface of the sample vial transfer assembly  52  as discussed more fully hereinbelow. A seal is disposed between the body  23  and the cap  56  so as to be capable of forming a substantially fluid-tight seal therebetween. 
         [0059]    Instead of a single anti-rotation lug  25 , the body  23  may include a plurality of lugs  25  disposed about a perimeter of the body  23 , such as the six equi-spaced lugs  25  of the embodiment of  FIG. 5 . While the lugs  25  may be disposed anywhere on the body  23  accessible to the sample vial transfer assembly  52  or related structure of the system  10 , the lugs  25  may be disposed advantageously proximate the open end of the body  23  and the cap  56 . In this manner, torque may be applied to both the body  23  and the cap  56  at approximately the same axial plane to minimize any induced moment in the vial  22  during removal and installation of the cap  56 . 
         [0060]    The sample vial body  23  may be manufactured from a substantially transparent or translucent material so that a level of the fluid sample therein can be readily discerned by the system operator to ensure the presence of a sufficient amount of fluid for subsequent processing. The body  23  may also include fluid level indicia  31  disposed on the outer surface thereof, such as a circumferentially-disposed frosted annular band. Accordingly, the vials  22  can be rapidly visually screened by the operator prior to loading in the vial tray  24  to prevent loading a vial  22  with too much or too little fluid which might not be processed successfully by the specimen preparing apparatus  18 . The fluid level indicia  31  may be provided in addition to the sample bar code label  58  discussed hereinabove. 
         [0061]    The cap may be manufactured from polypropylene or other suitable material and may include knurling  33  or other anti-slip feature along an outer perimeter thereof to facilitate manual handling by a nurse or doctor during sample procurement, as well as the system operator during manual loading and loading of the sample vial trays  24 . The cap torque pattern  27  may be at least one generally radially disposed rib  35 . In the embodiment depicted in  FIG. 5 , the torque pattern  27  includes six generally radially disposed, equi-spaced ribs  35 . 
         [0062]    The seal may be manufactured from any suitable material which can be sterilized and which is capable of withstanding attack by the preservative fluid, which may typically contain a solution of methanol in a buffer. For example, the seal may be manufactured from a multicomposite material such as a resilient rubber layer laminated with a suitable vapor barrier and may be disposed within the cap  56 . The cap  56  and the body  23  may have mating screw threads, a bayonet fitting, or other retention feature so as to be releasably engageable. In one embodiment, a substantially fluid-tight seal between the body  23  and the cap  56  may be formed when at least between about 5 and 50 inch-pounds of torque is applied to the cap  56  relative to the body  23 . A more typical torque range may be on the order of about 20 to 30 inch-pounds, with about 25 inch-pounds being preferred. To ensure that the fluid-tight seal is produced when the patient&#39;s cells are first disposed in the preservative fluid and to prevent leakage or evaporation of the preservative fluid during transport and storage, each of the cap  56  and the body  23  may include alignment markers  37 ,  39 , such that the alignment markers  37 ,  39  indicate a fluid-tight seal when at least aligned. 
         [0063]      FIG. 8  is a schematic perspective view of one design of a rotatable interface  142  disposed radially inwardly of the grippers  54  of the vial transfer assembly  52 . The interface  142  includes a torque pattern  144  for mating with the torque pattern  127  of the sample vial cap  56 . The rotatable interface  142  is shown inverted, to better depict the interface torque pattern  144  formed therein. In this embodiment, the interface torque pattern  144  includes six raised wedge-shaped sectors  146 . The sectors  146  are substantially equi-spaced about the interface  142 , which is rotatable about a longitudinal axis  148  thereof, and sized to mate with the torque pattern  127  of the cap  56 . Accordingly, the ribs  35  of the cap  56  fit in grooves  150  formed between the sectors  146  of the interface  142  and react against substantially vertical faces of the sectors  146  to permit both loosening and tightening of the cap  56 . 
         [0064]    To prevent rotation of the sample vial body  23  during these operations, the body  23  may be disposed in a bore  152  formed in the sample vial tray  24  having a unidirectional interface  154  along an edge  160  thereof for mating with the lugs  18  of the body  23 , as depicted in  FIG. 9A . The interface  154  includes six ramps  156 , each including a substantially vertical face  158  which abuts one of the body lugs  25 . Accordingly, the capped vial  22  may be disposed in the bore  152  with a flange  140  of the body  23  supported along the edge  160 . The rotatable interface  142  may then be engaged with and tighten the cap  56 , to ensure a fluid-tight seal prior to removing the vial  22  from the sample tray  24 . Due to the orientation of the ramps  156 , the lugs  25  react against the ramp faces  158  during tightening to positively secure and prevent rotation of the vial body  23 . 
         [0065]    Once the cap  56  has been tightened, the vial transfer assembly  52  may grasp the capped vial  22  about the circumference of the cap  56  with the grippers  54 , remove the vial  22  from the bore  152  in the tray  24 , rotate the vial  22  in front of the bar code reader  60 , and deposit the capped vial  22  in a bore  162  formed in a vial sleeve  164 , such as that depicted in  FIG. 9B  in wire form representation. The six lugs  25  of the capped vial  22  are received in every other one of twelve axially extending slots  166  formed along an upper edge  168  of the sleeve  164 , the flange  140  of the vial  22  being supported by the edge  168 . Once in the bore  162  with the lugs  25  disposed in the slots  166 , further processing may proceed. 
         [0066]    As discussed hereinabove, a slide  62  is printed and the slide indicia  82  verified as being readable and corresponding to the vial bar code label  58 . The vial  22  may then be uncapped and the sample collector  28  can be disposed in the vial  22  and rotated to disperse the cells in the sample. According to an alternative embodiment, once the capped vial  22  is disposed in the sleeve  164  and before the vial  22  is uncapped, the sleeve  164  may be rotated in one or both directions to disperse the cells in the preservative solution. Thereafter, a pin, clamp, or other structural feature of the system  10  may engage one of a series of notches  170  formed in a flange  172  of the sleeve  164  to prevent rotation of the sleeve  164  and the vial  22  disposed therein while the rotatable interface  142  engages and unscrews the cap  56 . The cap  56  is then retracted by the gripper  54  of the vial transfer assembly  52  and the sample collector  28  disposed in the preservative solution in the vial  22  to collect the cells against the filter  29  thereof and thereafter transfer the cells to the slide  62 . Once the cytological specimen has been prepared, the cap  56  is reoriented over the open vial  22  and screwed onto the body  23  until a substantially fluid-tight seal has been formed. The axially extending slots  166  which engage the lugs  25  form a bi-directional interface, to react against the body lugs  25  during both removal and installation of the cap  56  on the body  23 . Each of the axial slots  166  may be formed to include, optionally, a generally circumferentially disposed portion, shown generally at  174 , to lock a suitably sized lug against axial translation, if desired. 
         [0067]    Of course, other suitable materials, dimensions, and configurations for the body  23 , the cap  56 , the ribs  35 , the lugs  25 , the fluid level indicia  31 , and other features of the sample vial  22  will be apparent to those skilled in the art, those disclosed being provided as examples only. For example, while the mating ribs  35  and sectors  146  provide a positive, self-centering drive, other mating structure such as pins and annular tracks may be used. Further, the sample vial  22  may be used in other applications and contain other than cytological samples in preservative solution. 
         [0068]    The automated specimen preparing system  10  described herein employs certain specimen preparing innovations disclosed in the aforementioned patents in combination with batch processing capability to prepare gynecological and other cytological specimens in a highly efficient, reliable manner. The system  10  may also be used to batch process other specimens such as those including tissue samples, assay products, and other materials. Industry and regulatory acceptance of a system  10  and method in accordance with the teachings set forth herein are based, in part, on the capability to maintain one-to-one correlation between a patient sample and a specimen produced therefrom. Accordingly, a specimen is not produced on an unmarked slide  62 , or on a slide  62  on which the specimen indicia are not readable or do not correlate with the sample indicia bar code label  58  identified from the selected vial  22   a . By aborting the specimen preparing cycle prior to collection of the cells against the membrane  29 , unidentifiable or misidentified specimen slides are not produced, saving cycle time, consumables, and the patient&#39;s sample. 
         [0069]    When a patient&#39;s cells are first collected and deposited in a sample vial  22  prefilled with preservative solution, a preprinted bar code label  58  with a unique accession number is applied to the sample vial  22 . A second matching bar code label  58  is applied to a patient information sheet, listing relevant patient identifying information, as well as information regarding the tests or analyses to be performed on the specimen prepared from the sample. Accordingly, when data from the patient information sheet is entered into a database at a sample receiving area in a cytological laboratory, data from the bar code label  58  on the patient information sheet can also be input, either manually or preferably automatically using a laser scanner. The specimen produced from the sample with the matching bar code will therefore readily be identifiable as being from a particular patient. 
         [0070]    Once the system  10  is loaded with the samples and consumables by the operator, the system  10  runs in an automated manner under control of the processor  46  until all sample vials  22  are processed, or until such time as a system malfunction occurs or a consumable, such as a sample collector  28  or slide  62 , is depleted. To minimize the likelihood of the latter situation, sensors are provided throughout the system  10  to verify the presence of sufficient consumables to process all loaded samples prior to the initiation of automatic operation. Sensors may also be provided to monitor levels in the waste bottle  42  and waste bin  44 , so that the operator can be alerted to elevated levels of waste, which could interrupt processing during automatic cycling. 
         [0071]    Accordingly, when the operator initiates automatic processing, for example, by selecting “Start Batch” from a menu on the display or using a dedicated keypad input, the system  10  checks that sample vials  22  are loaded and a minimum number of necessary consumables and staining racks are available to complete processing of all the samples. If sufficient consumables and waste capacities exist, the system  10  starts the automatic sample processing cycle. The cycle continues until all of the loaded sample vials  22  have been processed, the operator manually interrupts the cycle, or a system error occurs which cannot be automatically rectified. If insufficient consumables or waste capacities exist, the operator may correct the condition or, alternatively, override the system  10  and initiate automatic processing anyway. In the event a prior automatic cycle had been interrupted, “Start Batch” may be used to resume automatic cycling at the point of interruption, after checking system consumables and capacities. In order to protect the operator from injury by moving components during automatic cycling, access points such as the upper cover  14  may be interlocked. 
         [0072]    If the operator chooses to interrupt the automatic cycle prior to completion, the operator may select “Interrupt Batch.” Upon receipt of the interrupt signal, the processor  46  interrupts the automatic cycle in an orderly manner, for example, by completing preparation of a specimen in process, transferring the completed specimen slide  62  to a staining rack  34  in the unloading area  36 , and capping and returning the selected sample vial  22   a  to the vial tray  24 . After that sample processing cycle has been completed and moving components are at rest at respective home positions, the operator access interlocks are unlatched and the operator is notified. The operator may then open the upper cover  14  or access other internal areas of the system  10 , as desired. 
         [0073]    A “Maintenance” function can also be provided in which the system  10  supports operator level maintenance activities such as jogging of the moving components to or from respective home positions to provide the operator access to various interior volumes of the system  10 , for example, to clear a jam or to retrieve a mishandled slide  62 . Other maintenance functions may include emptying of the waste bottle  42  and bin  44 , priming of the fixative coating station  38  with the fixative solution, and advancing of paper in the system printer  48 . The system  10  may also provide operator selectable diagnostic tests to facilitate system troubleshooting or verify proper system operation. For example, a pneumatic test may be initiated of the vacuum system  88  of the specimen preparing apparatus  18  to ensure sufficient volumetric flow rate and negative pressure level. A display test could be used to verify display operation. 
         [0074]    A usage log may be provided to track total number of samples processed, total number of specimens produced, total system run time, and other relevant usage parameters. The processor  46  may also maintain an error log which lists, for example, the last fifty errors detected by the system  10  and which may be displayed or printed at the discretion of the operator. A typical log entry may include date and time of the error, sample indicia and tray location, and disposition or corrective action. In one embodiment, the system  10  identifies any sample vial  22  from which a specimen was not successfully prepared, along with the reason for the failure, such as “sample too dense” or “cap too tight.” 
         [0075]    Detectable conditions that could cause specimen quality problems are flagged by the system  10  and noted to the operator on the display and paper printout. If possible, a partially collected specimen is returned to the vial  22  and preparation of the slide  62  is aborted. If the problem is associated with a particular selected sample vial  22   a , the system  10  recovers after returning the selected vial  22   a  to the vial tray  24  and recording the error, processing the remaining sample vials  22  in the batch. However, if the error is a system level problem, such as a motor or sensor failure, jammed mechanism, or other malfunction that is not automatically recoverable and requires operator or qualified service personnel intervention, the automatic cycle is halted and the error recorded and reported to the operator. 
         [0076]    Upon installation or commissioning of the system  10 , or thereafter as required, the processor  46  may be initialized and setup functions enabled or disabled. For example, the date and time may be input, as well as the respective formats thereof. The system printer  48  may be directed to automatically print diagnostic test results or sample processing data at the end of every automatic batch cycle. A date/time stamp may be enabled to print the date and time a specimen was prepared on the frosted end  68  of each slide  62 , in addition to the slide indicia  82 . Optionally, the name or other identifier of the cytological laboratory preparing the specimen with the system  10  may be printed on the slide  62  as well. 
         [0077]    While there have been described herein what are to be considered exemplary and preferred embodiments of the present invention, other modifications of the invention will become apparent to those skilled in the art from the teachings herein. For example, while the system  10  and method have been described for preparing a single specimen from each sample vial  22 , the system  10  could be programmed to permit two or more specimens to be prepared from a single sample vial  22 . In such instances, the slide indicia  82  could include an additional character or identifier to indicate the first specimen, second specimen, third specimen, etc. Alternatively, the sample vial  22  could be reprocessed by inserting the vial  22  in a tray  24  in a next batch for a subsequent automatic cycle. 
         [0078]    The disclosed components of the system  10  may be manufactured in various sizes, configurations, and materials. Additionally, the system  10  may be used to prepare specimens from non-gynecologic cytological samples, such as cells sourced from fine needle aspirates, from mucoid specimens taken from respiratory and gastrointestinal tracts, from body fluids such as serous effusions and urinary and cerebrospinal fluids, from superficial brushings and scrapings from oral cavities, nipple secretions, skin lesions, and eye brushings, and from other sources. 
         [0079]    The particular methods of manufacture and particular arrangements of discrete components, geometries, and interconnections therebetween disclosed herein are exemplary in nature and are not to be considered limiting. It is therefore desired to be secured in the appended claims all such modifications as fall within the spirit and scope of the invention. Accordingly, what is desired to be secured by Letters Patent is the invention as defined and differentiated in the following claims.