Patent Document

CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the priority of the German patent application DE 102008054071.4 having a filing date of Oct. 31, 2008. The entire content of this prior application DE 102008054071.4 is herewith incorporated by reference. 
     BACKGROUND OF THE INVENTION 
     The invention relates to a method for operating a tissue processor, and to the tissue processor. The tissue processor comprises at least one retort for receiving the tissue samples, and at least one container for stocking a process medium. 
     Biological tissue samples, in particular histological tissue samples, are often required in the fields of human and veterinary medicine, in particular as microscopic prepared specimens for the assessment of cells and their environment. For microscopic inspection, thin sections of the tissue sample must be prepared for assessment under the microscope, in incident or transmitted light, by an expert. 
     The production of thin sections, for example using a microtome, requires that the tissue sample have a certain strength so that thin, transparent sections having a thickness on the order of micrometers can be produced using a knife. For this purpose, the tissue sample must first pass through a treatment process in which it is fixed, dehydrated, cleared, and then infiltrated with a carrier material, preferably melted paraffin. These processes are often performed successively in a single unit called a “tissue processor”; this tissue processor contains for this purpose a closable process chamber called a “retort” that receives the various reagents, in particular process media, for carrying out the process steps at a suitable temperature and pressure. 
     One important process step in this context is infiltration of the tissue sample with the carrier material in order to stabilize and consolidate it. This infiltration process step is preceded by a clearing step in which alcohol residues still present from a preceding dehydration step are removed. The chemical solution used for this clearing step is xylene or a similar medium. In the subsequent infiltration step, in which the tissue sample is exposed to the carrier material (usually melted paraffin), xylene constituents that still remain are flushed out and taken up by the liquid carrier material, with the result that the carrier material in the retort becomes contaminated. Residual dehydration reagents are likewise removed during the clearing step. Constituents from the tissue sample itself can also contaminate the dehydration reagents, the clearing reagents, or the carrier material. It is therefore necessary to divide the individual process steps into multiple process substeps in which the tissue sample is exposed successively to a reagent of increasing purity. 
     If the infiltration process is divided into three process steps, for example, the tissue sample is then first treated, in a first process substep, with a first carrier material that can have a relatively high level of contamination (e.g. with xylene). This is followed, in a second process substep, by a second infiltration step using a second carrier material that has a higher degree of purity than the first carrier material. Lastly, the tissue sample is exposed, in a third process substep, to a third carrier material that has the highest degree of purity; the carrier materials can encompass the same or different reagents. In this fashion the tissue sample is completely infiltrated, in a process of substeps with carrier material of increasing purity, with carrier material that has sufficient quality to produce a good thin section in a microtome, and for a microscopic prepared specimen. 
     The use of multiple liquid process media having different degrees of purity requires that these process media be kept available in containers in a liquid state. If one of the process media is too highly contaminated, this usually affects the aforesaid first process medium, and it must therefore be replaced with a process medium having an improved degree of purity. 
     It is an object of the invention to describe a method for operating a tissue processor, and a tissue processor, that contribute in simple fashion to reliable operation of the tissue processor and/or to high quality in the completely processed tissue samples. 
     This object is achieved by a method for operating a tissue processor that is provided for the processing tissue samples and that comprises at least one retort for receiving the tissue samples and at least one container for receiving a process medium, said method comprising: transferring the process medium at least one of from the container into the retort and from the retort into the container; automatically measuring a measured value in the course of transferring the process medium, the measured value representing a characteristic property of the process medium; and identifying the process medium based on the measured value. 
     The tissue processor for performing the aforementioned method according to the invention comprises at least one retort for receiving the tissue samples; at least one container for receiving a process medium; a transfer mechanism for transferring the process medium at least one of from the container into the retort and from the retort into the container; an automatic measuring device for measuring a measured value in the course of transferring the process medium, the measured value representing a characteristic property of the process medium; and an identifier for identifying the process medium based on the measured value. 
     According to the invention, during the operation of a tissue processor a process medium is conveyed from a container into a retort, or from the retort into the container. The tissue processor is provided for the processing of tissue samples. The retort is provided for receiving the tissue samples. The container is provided for stocking the process medium. Upon conveyance of the process medium, a measured value that is representative of a characteristic property of the process medium is automatically acquired. Conclusions can therefore be drawn from the acquired measured value as to the characteristic property, and from the characteristic property as to the process medium currently being conveyed. The characteristic property is, for example, a density and/or a degree of purity of the process medium. 
     This makes it easy to detect whether the correct process medium for the next process step or process substep has been introduced into the retort, especially when multiple process media and/or process media having different degrees of purity are provided in corresponding containers, and thus contributes to reliable operation of the tissue processor. In other words, it is thereby possible to detect whether a container having one of the process media has been connected in error. It is further possible, without exchanging the erroneously connected container, to use the process medium stocked therein automatically for the correct process step or process substep. 
     Acquisition of the measured value, and detection, associated therewith, of the process medium being conveyed, furthermore makes it possible to detect, after a process step, whether the process medium is subsequently usable for the same process substep, or whether the process medium is so greatly contaminated that it can be used subsequently for a different process substep or must be replaced. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The process medium can be, for example, a fixing reagent, a dehydration reagent, an intermedium, a carrier material, or a cleaning reagent, in particular alcohol or xylene. In this context, “different process media” refers to reagents that are inherently chemically identical and have a slightly different degree of purity, or to reagents that are chemically entirely different. At least one sensor, which is preferably provided between the container and the retort in the flow direction, is provided for acquiring the measured value. If the process media differ from one another in such a way that different sensors are required in order to detect their characteristic properties, a sensor module can be provided that comprises the at least one sensor and corresponding further sensors. 
     During processing of the tissue sample in the retort, the process medium or media is/are regularly conveyed, in particular pumped, from the corresponding containers to the retort and back again. In this context, they are guided past the sensor in such a way that the latter can acquire the measured value and thus enable a determination of the characteristic property. Acquisition of the measured value is preferably carried out both upon pumping of the process medium to the retort, and upon pumping of the process medium back to the corresponding container. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Exemplifying embodiments of the invention are explained below with reference to the appended drawings, in which: 
         FIG. 1  shows a tissue processor; 
         FIG. 2  shows various components of a tissue processor relevant to the infiltration of tissue samples with paraffin; 
         FIG. 3  shows various components of a tissue processor relevant to dehydration, cleaning, or intermediate processing of the tissue samples; 
         FIG. 4  is a flow chart of a first program for operating the tissue processor; and 
         FIG. 5  is a flow chart of a second program for operating the tissue processor. 
     
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     Identical parts are labeled identically in the various Figures. 
       FIG. 1  schematically shows a tissue processor  10  with which the method according to the present invention can be carried out. Tissue processor  10  contains a retort  12  for processing tissue samples with different reagents. In said retort  12 , the tissue samples pass through multiple process steps. A fixing process, in which formalin is typically used, preferably occurs first. A dehydration process is then accomplished, using alcohol solutions of various degrees of purity. In a subsequent clearing process, alcohol residues are removed from the tissue samples and the tissue samples are prepared for the uptake of carrier material. Xylene or a similar medium is often used in this clearing process. Paraffin or wax of various compositions is preferably suitable as a carrier material. Individual or multiple process steps can be subdivided into process substeps in which the tissue samples are exposed to the aforesaid reagents having different degrees of purity, for example, within one of the process steps, to one of the reagents having an increasing degree of purity. 
     Once these process steps have been executed, a process of cleaning the retort  12  is carried out using the aforesaid, or further, reagents, for example by performing the aforesaid process steps in reverse order without tissue samples in retort  12 . 
     Tissue processor  10  comprises a cabinet  13  having drawers. One drawer  14  serves for the reception of containers  15  having the reagents (only two of many being shown) that are necessary so that the fixing process, the dehydration process, and/or the clearing process can be carried out. Drawer  14  has a handle  16  for actuation. A further drawer  17  (only partially shown) contains components for the infiltration process described below. 
     A work area  20  is provided on a desktop  18 . Also arranged on desktop  18  is a control device  22  having a screen  24 . Control device  22  controls the treatment processes for the tissue samples with the assistance of a computer. 
       FIG. 2  shows important components for carrying out the method for infiltrating tissue samples with carrier material, in particular paraffin or wax. 
     Retort  12  is embodied as a sealable chamber having an opening  30  that can be closed off. Inside retort  12 , the various reagents, in particular the paraffin that is important for the infiltration process, can be acted upon by pressure, vacuum, and temperature. The interior of retort  12  is connected via a valve arrangement  32  to lines  40 ,  42 ,  44  via electrically controllable valves  34 ,  36 ,  38  respectively. 
     Line  42  is connected via valve  36  to the contents of retort  12 . Under the control of valve  36 , liquid paraffin is delivered in and back out through line  42 . A further line  44  serves for connection to further containers  15  having the reagents for the fixing process, the dehydration process, and/or the clearing process, as will be described below. 
     Line  42  is connected to a distributor  46  that distributes liquid paraffin under the control of valves  48 ,  50 ,  52 ,  54 . Connected to distributor  46  is line  56 , which connects the distributor to a supply station  58  for paraffin. Supply station  58  is embodied as a drawer, and contains extension rails  60  and a handle  62 . 
     Also connected to distributor  46  are three lines  64 ,  66 ,  68  that connect it to a first container  70 , a second container  72 , and a third container  74 . These containers  70 ,  72 ,  74  contain liquid paraffin with an increasing degree of purity. Containers  70 ,  72 ,  74  are also configured as drawers, and can be pulled out of the chamber of tissue processor  12  and then removed. 
     All the lines  40 ,  42 ,  56 ,  64 ,  66 ,  68  are heated, as are distributor  46  and, depending on the reagent used, valve arrangement  32  as well, in order to ensure that the paraffin is always kept in a liquid state, e.g. at 65° C., and does not solidify during operation. The same is also true of retort  12  and its parts, and of supply station  58  and containers  70 ,  72 ,  74 . The corresponding heating elements have been omitted from the Figure for reasons of clarity. 
     Supply station  58  has a considerably larger volume than the respective container  70 ,  72 ,  74 . It also serves to melt paraffin that is present in the solid state as paraffin pellets or flakes. The bulk volume of paraffin pellets or flakes is considerably larger than the liquid volume of the melted paraffin for the same weight. The enlarged volume of supply station  58  thus allows a sufficiently large bulk volume of solid paraffin to be introduced, with no need to add more solid paraffin for a sufficient liquid supply. This facilitates the handling of solid paraffin. In addition, the liquid volume of supply station  58  is also sufficiently large that containers  70 ,  72 ,  74  can be provided with uncontaminated paraffin for a relatively long operating time, for example even for automatic operation during the night, when operators do not need to be present. 
     A sensor  78  is arranged between containers  70 ,  72 ,  74 , and retort  12 , in particular between distributor  46  with its valves  48 ,  50 ,  52 ,  54 . Sensor  78  is provided for acquisition of a measured value MESS ( FIG. 4 ) that is representative of a characteristic property CHAR of the paraffin, in particular of a degree of purity of the paraffin, that is currently flowing through line  42 . It is thus possible, as the paraffin is being pumped to retort  12  and back to containers  70 ,  72 ,  74 , to ascertain the different degrees of purity of the paraffin currently being used, before and after treatment of the tissue samples. Sensor  78  is, for example, an optical sensor that senses a turbidity or coloration of the paraffin; the paraffin can be treated with a coloring agent in order to ascertain its degree of purity. Alternatively thereto, using sensor  78  it is possible to ascertain a density or a conductivity of the paraffin, as a function of which the degree of purity can then be ascertained. 
       FIG. 3  shows system bottles  80  that each comprise a connector  82  for a line  86  for pumping off a process medium, and a connector  84  for applying pressure to system bottles  80 . System bottles  80  furthermore comprise closures  88  through which the process medium can be introduced. System bottles  80  can also be referred to in this context as containers for process media. 
     What is contained in the different system bottles  80  is, in principle, the chemically identical process medium, the different system bottles  80  each containing the corresponding process medium at different degrees of purity. The process media having different degrees of purity can also be referred to in this connection as different process media. 
     Further process media having different degrees of purity can be stocked in stations  90  having different baths  96 . Stations  90  each comprise a line  92  for transporting the corresponding process medium, and a compressed-air connector  94  for applying pressure to the stations. Connector  92  communicates via a line  98  with a rotary valve  100 . Stations  90  can also be referred to in this connection as containers for process media. 
     Depending on a switch position of rotary valve  100 , line  86  or line  98  communicates with line  102  that leads from rotary valve  100  to coupling part  104 . A density sensor  106  and a pressure sensor  108  are arranged on coupling part  104 . Density sensor  106  and pressure sensor  108  allow the density of the process medium that is currently flowing through coupling part  104  to be sensed. The degree of purity of the process medium can be determined as a function of its density. Density sensor  106  and pressure sensor  108  thus constitute a sensor module for acquiring a measured value that is representative of the degree of purity of the process medium. Density sensor  106  is suitable in particular for ascertaining the degree of purity of alcohol or xylene. It is additionally possible to detect, with the sensor module, whether alcohol, xylene, or paraffin is currently being pumped. 
     The process media that are stocked in stations  90  or in system bottles  80  encompass, for example, fixing reagents, in particular alkaline fixing reagents, for example formalin; dehydration reagents, in particular alcohols, in particular ethanol; intermedia, for example isopropanol or aromatic compounds, in particular xylene; and/or cleaning reagents, in particular distilled water. In addition, the fixing reagents, dehydration reagents, and/or intermedia can also be used for cleaning and, in this context, can also be referred to as cleaning reagents. One or more other sensors can also be provided alternatively to density sensor  106  or pressure sensor  108 . What is important here is that the degree of purity of the respective process medium can be determined with the corresponding sensor. The sensor module preferably comprises exactly as many sensors as there are characteristic properties CHAR ascertainable for all the process media used. Characteristic property CHAR can also, for example, be achieved [sic] by means of a photosensor, a conductivity measurement, and/or by means of a measurement of a pH value of the corresponding process medium. 
     The tissue samples are then subjected successively to the individual process steps, and thus successively exposed to the different process media. Within the process steps, the tissue samples are exposed successively, within the process substeps, to the process media having different degrees of purity. During treatment with chemically identical process media having a different degree of purity, the tissue samples are exposed to the process media preferably with an increasing degree of purity. In contrast thereto, in order to clean retort  12  the process media can be used in reverse order, in particular with a decreasing degree of purity. 
     A first program ( FIG. 4 ) is preferably stored on a storage medium of a control apparatus for operating the tissue processor. The program serves, upon pumping of the process medium to retort  12 , to automatically determine characteristic property CHAR of the process medium currently being used, and to decide automatically whether the process medium currently being used is suitable for the subsequent process step and/or process substep. 
     The first program is preferably started at a step S 2  in which, if applicable, variables are initiated, by preference upon pumping of the process medium to retort  12 . 
     In a step S 4 , a measured value MESS of sensor or sensors  78 ,  106  is acquired. 
     In a step S 6 , characteristic property CHAR is ascertained as a function of measured value MESS. For this purpose, for example, a database can be stored on the storage medium, in which database the various measured values MESS have allocated to them the corresponding characteristic properties CHAR and/or the corresponding process medium. 
     A step S 8  checks whether characteristic property CHAR that has been ascertained corresponds to a predefined target property SP_CHAR. Target property SP_CHAR is predefined, for example, by the subsequent process step or subsequent process substep. In order to carry out the first substep of the dehydration process, for example, a check is made as to whether the process medium pumped to retort  12  is the alcohol having the lowest degree of purity. Alternatively or additionally, in order to carry out the second substep of the clearing process, a check is made as to whether the process medium currently being pumped to retort  12  is xylene of a medium degree of purity. If the condition of step S 8  is met, the process medium currently being used then corresponds to the process medium necessary for the subsequent process step or process substep, and processing continues in a step S 12 . If the condition of step S 8  is not met, the process medium currently being used does not correspond to the process medium necessary for the subsequent process step or process substep. The program is then continued in a step S 10 . 
     In step S 10 , pumping of the process medium to retort  12  is interrupted, the process medium is pumped back into the corresponding container, and the process medium is reclassified in accordance with characteristic property CHAR that has been ascertained. The process medium can then subsequently be used automatically for a different process step or process substep with no need to exchange the corresponding container manually, or to manually modify a connector of the corresponding container. In addition, one or more cleaning steps can subsequently be carried out in order to remove, from retort  12  and/or from the lines, the process medium that was erroneously introduced. 
     The first program can be terminated in a step S 12 . By preference, however, the first program is executed on a regular basis upon pumping of one of the process media to retort  12 . 
     A second program ( FIG. 5 ) is preferably stored on the storage medium. This program serves, upon pumping of the process medium from retort  12  to the corresponding container, to determine automatically the characteristic property CHAR of the process medium currently being used, and to decide automatically whether the process medium currently being used is still suitable in future for the same process step and/or process substep. 
     Steps S 14  to S 20  of the second program correspond substantially to steps S 4  to S 8  of the first program, the second program preferably being started in step S 14  when the process medium is being pumped from retort  12  to the corresponding container, and a check being made in step S 20  as to whether, for example, the process medium currently being used still has the same degree of purity as it did prior to the last process substep that was carried out. If the condition of step S 20  is met, the process medium can be used in future for the same process substep, and processing can be continued in a step S 24 . If the condition of step S 20  is not met, the process medium then cannot be used in future for the same process substep, and processing is continued in a step S 22 . 
     In step S 22 , a reordering of the process media occurs, preferably without exchanging the containers or the process media themselves. In particular, a process medium classified as third process medium MED 3  is classified as subsequently second process medium MED 2 , and thus subsequently used no longer for a third of the process substeps but rather for a second of the process substeps. The current second process medium MED 2  is classified as subsequently first process medium MED 1 , and subsequently used for a first of the process substeps. The process medium currently classified as first process medium MED 1  is switched out by means of a replenishing instruction NEW and replaced by a new process medium having a highest degree of purity, and subsequently classified as third process medium MED 3  and used for the third process substep. The contaminated process media are thus not replaced always by process media having a highest degree of purity, but instead in principle by a process medium having the next-higher degree of purity. In this context, the process media preferably are not moved by pumping, but are merely classified differently. 
     The second program can be terminated in step S 24 . The second program is, however, preferably executed again each time the process medium is conveyed from retort  12  back to the corresponding container. 
     The invention is not limited to the exemplifying embodiments indicated. For example, all the process media can be moved to the retort  12  via only one line, or even more lines can be present for the aforesaid, or further, process media. The number of sensors provided then preferably decreases or increases correspondingly. In addition, the sensors can be arranged very close to the valve, the containers, or retort  12 , for example within the same housing. The two programs can moreover be implemented in one program, or subdivided into further subprograms. 
     LIST OF REFERENCE NUMERALS 
     
         
           10  Tissue processor 
           12  Retort 
           13  Cabinet 
           14  Drawer 
           15  Reagents 
           16  Handle 
           17  Drawer 
           18  Desktop 
           20  Work area 
           22  Control device 
           24  Screen 
           30  Opening 
           32  Valve arrangement 
           34 ,  36 ,  38  Valves 
           40 ,  42 ,  44  Lines 
           46  Distributor 
           48 ,  50 ,  52 ,  54  Valves 
           56  Line 
           58  Supply station 
           60  Extension rails 
           62  Handle 
           64 ,  66 ,  68  Lines 
           70  First container 
           72  Second container 
           74  Third container 
           78  Sensor 
           80  System bottles 
           82 ,  84  Connectors 
           86 ,  98  Lines 
           88  Closures 
           90  Stations 
           92 ,  94  Connectors 
           96  Baths 
           100  Rotary valve 
           102  Line 
           104  Coupling part 
           106  Density sensor 
           108  Pressure sensor 
         START Program start 
         MESS Measured value 
         CHAR Characteristic property 
         SP_CHAR Target property 
         THD Threshold value 
         MED 1  First process medium 
         MED 2  Second process medium 
         MED 3  Third process medium 
         END Program end 
         S 2  to S 12  Method steps

Technology Category: g