The invention concerns a method for cross-referencing the identification of object supports for microtomised tissue samples to be disposed thereon, with cross-reference to an identification information of a support of an associated, not yet microtomised tissue sample.
The invention also concerns a device for carrying out such a method and a device for preparing to carry out the method to identify object supports of microtomised tissue samples with cross-reference to identification information of a support of a not yet microtomised tissue sample, wherein the support is provided with an information carrier for cross-reference, and the device comprises a means for generating the identification information.
Examination of tissue samples from patients is a routine procedure in histological technology. The most common method consists of embedding the tissue samples in paraffin, cutting them with microtomes, staining them in a further process, covering them with a cover glass and supplying them to a microscope for diagnostic evaluation. In modern laboratories, the patient samples are automatically processed during the individual steps. The samples are initially prepared through the following steps: fixing, dehydration, clearing with an intermediate medium, and embedding in paraffin in an embedding device. Production of a paraffin block is realized in a pouring station. Microscopic, thin slices are produced through cutting the paraffin block, with an embedded tissue sample, in a microtome. The thin slice thereby obtained is stained and contrasted in several steps in a staining device. After covering the thin slice with a cover glass on a cover glass covering device, the thin slice obtained from the patient sample is ready for evaluation under a microscope.
One problem consists in maintaining unique identification of the tissue samples to prevent confusion and loss of samples throughout all of the processing steps. Some progress has been achieved in this regard. In modern processing, immediately after cutting, the tissue sample is inserted into a so-called tissue cartridge which is closed and secured by a lid. In addition to good liquid flow properties, modern tissue cartridges also offer distinct features to prevent loss of the sample and to provide unique identification. Towards this end, modern cartridges have a writing or printing surface of sufficient size and surface quality to permit writing or printing with sufficient adhesion and durability during the subsequent processing. In this fashion, the sample can be clearly identified in the identified cartridge during embedding of the tissue. In the subsequent step, i.e. pouring the paraffin block around the tissue sample, the risk of sample confusion is still sufficiently prevented, since the same identified cartridge serves as support of the paraffin block with tissue sample, wherein the sample is connected to the identified cartridge via the solidified paraffin block.
In the next step, microscopic thin slices of the tissue sample are produced on a microtome. Towards this end, the paraffin block with embedded tissue sample and connected cartridge support part are clamped into the sample holder of a microtome and microtomised. Thin slices are thereby produced on the back of the microtome knife or on the edge of one-way blade holders, which are transferred manually, using a brush and tweezers, to a warm water bath for stretching the slices. The stretched, thin slices are then placed on a conventional, glass object support. The labelling field of the object support must now have the same allocating information concerning the tissue as is written on the tissue cartridge serving as the support. Conventionally, several usable thin slices are produced from one tissue sample and are distributed on several object supports. This means that several object supports must contain the same identification as to origin of the tissue sample.
The object support can be labelled by hand-writing as soon as the thin slices have been produced. The patient tissue information provided on the cartridges is thereby transferred onto one or more object supports through hand-writing. Clearly, this method increases the danger of transfer errors and therefore offers little protection from confusion and errors. Additionally, the hand-written information must be read and further processed by other persons at a later time.
U.S. Pat. No. 4,276,253 discloses mounting an identification on the sample which is maintained for each microtomised sample tissue during cutting, i.e. is reproduced. There is no allocation problem since the microtomised tissue sample is already characterized during cutting. This requires extensive identification of samples using shaped, elongated labels which are also cut. This requires an increase in size of the paraffin block being cut and also entails time-consuming embedding of these labels. The considerable technical effort renders practical applications doubtful.
Further documents (WO 00/62035, U.S. Pat. No. 5,854,075; U.S. Pat. No. 5,746,855 and DE 100 10 140 A1) describe automated processes which eliminate allocation problems. Such full automation is problematic due to the extremely thin slices and can only be realized with considerable technical effort.
A method and devices of the above-mentioned type with manual cross-reference are also known, wherein one or more object supports are labelled with the same information at the same time when the tissue cartridge, which serves as support, is labelled at the start of the sample preparation process. This reduces the risk of confusion, in particular when the writing is carried out automatically with a coupled cartridge and object support printing system. This method is disadvantageous in that the previously labelled object supports cannot accompany the patient sample with tissue cartridge as one integrated unit in the subsequent steps. This means that, after microtomising of a tissue sample, the matching previously labelled object supports must be found and identified through manual comparison of the written information. A further disadvantage is the fact that the number of object supports required for each tissue sample cannot be exactly predetermined at the time of labelling since, in addition to the specifications of the doctor, this number also depends on the assessment of the expert carrying out microtomisation. In practice, it is very difficult to adhere to a systematology which ensures cross-reference of the object support and tissue sample of the patient by allocating previously labelled object supports, since the samples must be relocated several times during the individual preparation steps. For this reason, the object support must disadvantageously be located in intermediate positions and comparative readings are required to provide a new cross-reference.
Pre-fabricated object supports with corresponding identification are difficult to allocate and would also have to be reproduced or be provided in excessive numbers when the expert providing the thin slices thereby realizes that more microtomised tissue samples are required than expected by the doctor. This problem increases when the object support identification must contain further information concerning different processing and evaluation, in addition to the cross-reference to the patient.
It is therefore the underlying purpose of the present invention to provide a safe and efficient identification method for object supports and provide devices therefor which simplify the described cross-referencing problems in histological technology, in particular those occurring during manual cross-referencing.
This object is achieved with a method of the above-mentioned type in that the identification information which belongs to the support is automatically detect during arrangement thereof in the microtome, and an identification to be associated therewith is automatically transferred to at least one object support and subsequently, with only this object support bearing the identification being provided at the work place of the microtome to the technician working on the microtome for the manual mounting of a microtomised tissue sample at the time when the microtomised tissue sample must be disposed on an object support.
This object is achieved with respect to the device for carrying out this method in that the device comprises a detecting means for detecting the identification information while the support comprising a non-microtomised tissue sample is disposed in the holding means of a microtome, and a labelling means for providing an object support with an identification, a transfer means for information transfer between the detecting means and the labelling means and a discharge means installed at the work place of the microtome for removal, by the technician working on the microtome, of object supports provided with an identification, for manual mounting the microtomised tissue sample.
The inventive method assumes the complete task of the expert producing the microtomised samples, i.e. the thin slices, of allocating these samples to the non-microtomised tissue sample. In this connection, non-microtomised tissue samples also include such tissue samples from which the first thin slices have been cut off. The automated detection mainly permits detection thereof when the support including tissue sample is located in the microtome. This is not possible in a reliable manner using the human eye, since the identification cannot be easily read due to the restricted space. The invention avoids detection outside of the microtome, since one cannot guarantee that the detected tissue sample is actually clamped. Labelling errors of the object supports are eliminated through automatic detection of the identification information during clamping of the support as well as through automatic transfer and identification. Transfer may be effected electrically, optically, through infrared, radio waves or in another manner.
The reliability is further ensured, when the expert has only one such object support at a time whose identification as to origin coincides with the microtomised tissue sample, since at the moment during which the expert must place the microtomised tissue sample onto an object support, only the object support having the correct identification is available. All human allocation is avoided. The avoidance of any such allocation also eliminates the associated occurrence of errors. Even when the expert interrupts microtomising of a sample to process another sample in the meantime, no allocation problems can occur, since only one object support is available at a time: namely, the object support having an identification associated with the identification information of the tissue sample located in the microtome. Identification information and identification can thereby be connected physically or electronically to the support and the object support. In the latter case, a physically allocated identification code simplifies electronic allocation. The latter solution is to be preferred for large amounts of data or when a physical information link with extensive data is problematic due to the required processing.
The inventive device provides the means required to carry out the inventive method. These means provide that production and provision of the correctly labelled object support—and only this support—is possible automatically and “just in time” at the location where required and in the desired amount.
Clearly, the method and device are not restricted to the above-mentioned technique for providing microtomised tissue samples, since the inventive solution does not depend on the manner in which the tissue sample is treated and cut. The device may comprise a microtome, with the knife being moved or with the knife being fixed and the sample being moved. One of these elements can be moved on a slide or a rotating disc and be manually or automatically driven. Of course, a laser beam or another method for producing tissue slices can also be used. The tissue slices may be human, animal, or plant tissue slices.
In the device of the above-mentioned type for preparing an identification of object support, this means, the information carrier, and a data carrier associated with the support are designed to produce identification information which contains, in addition to identification as to the origin of the tissue sample, an information distribution key and information which provides an individual information content for identification of several object supports with microtomised tissue samples which are derived from the same, not yet microtomised tissue sample.
This device prepares labelling of the object support in that the required information is stored as identification information such that it is linked mechanically or electronically with the support of the sample tissue such that, on this basis, the above-mentioned method can be carried out with the above-mentioned device, wherein this device for preparing the identification includes applications with which the identification information contains cross-reference information providing individual information content for individual object supports having thin slices derived from the same tissue sample. In this manner, not only correct allocation of the identification of object supports for microtomised tissue samples with the corresponding not yet microtomised tissue samples is obtained but it is also ensured that a desired number of tissue slices is produced on object supports having the desired additional information.
Further developments of the method and of the mentioned devices and the inventive processing device are described below.
The inventive method is advantageously further developed such that every time a microtomised tissue sample is produced, the identification information is detected and an object support having an identification is produced and offered. This ensures that an object support is provided for each microtomised tissue sample. It is thereby possible to assure that the object support is produced only when the expert working on the microtome regards the microtomised tissue sample as useful and initiates production of the identified object support.
In the simplest case, the identification of the at least one object support contains the same identification information which is associated with the non-microtomised tissue sample. In most cases, only reference is thereby made to the origin of the non-microtomised tissue sample or to the corresponding patient. The identification information may contain further information in addition to the identification as to origin. Such information may include pre-treatment of the tissue sample, date or place of removal or organ of removal. Further information is feasible, as will be exemplified below.
If different treatment or different evaluation of the microtomised tissue samples is required or their sequence is to be fixed, it is advisable to load the identification of the object support with further information, in addition to identification as to origin, using an information distribution key to individualize individual microtomised tissue samples on the object supports, which are derived from the same non-microtomised tissue sample. This permits further treatment and evaluation on the basis of the identification and avoids the necessity of separately adding such information to the object supports. This also reduces associated problems in histological technology. The information processing key and the further information are advantageously contained in the identification information and thereby physically or electronically connected to the support and thereby to the non-microtomised tissue sample.
The device for carrying out the above-mentioned method may be designed in different ways. The detecting means may be designed such that it detects the identification information after positioning of the support in the microtome and initiates identification of at least one object support. The detecting means may also be designed such that the identification information is detected when a microtomised tissue sample is produced and a command is issued to the identification means to initiate labelling of an object support. Continuous detection of the identification information and labelling of object supports is also possible if required e.g. by pressing a button.
Identification information and identification may, of course, be designed in the most different of ways. It may be in writing which can be read by a person, or be mechanically evaluated such as e.g. a bar code, or also be a magnetic or electronic storage medium of any type. The identification information or identification can thereby be provided on a separate data carrier which can be allocated to a support or an object support by means of an identification code. In this case, it must of course be ensured that only the correct allocation is admissible. This solution is advantageous when additional data must be allocated, usually in the form of additional identification information. It is often sufficient and straightforward to load the identification information on an information carrier which is physically connected to the support.
To prevent an object support of the previously processed tissue sample from remaining in the discharge means thereby producing an allocation error, it is advisable to design the discharge means such that it interrupts presenting an object support provided with an identification when a new support is placed in the microtome. Towards this end, the discharge means may reject or withdraw the remaining object support to write new information on it.
Should the device perform functions in addition to the pure copying of identification as to origin, it is advantageous to provide it with a controller for labelling the object support. If such a controller is provided it is moreover advisable to provide the device with a command input for determining the type and/or number of identifications. This command input maybe a manual command input or a command input through identification information. An external command input via a data line connected to a computer or command input via a data carrier is also feasible.
The device, preferably the identification means, should comprise a depot for non-identified object supports which should be large enough to be able to produce labelled object supports of sufficient number without requiring constant recharging.
The controller may be designed such that the number of the object supports to be provided with an identification can be predetermined. This corresponds to the fact that the doctor generally decides how many microtomised tissue samples are required on object supports. Moreover, the controller should be designed such that the number of object supports to be labelled can be manually increased. This addresses the fact that the expert working on the microtome will often realize that more object supports are required than are predetermined, either because the quality of the tissue sample is doubtful or the expert can see already from the thin slice that it is peculiar and more thin slices are required for diagnosis.
As mentioned above in connection with command input, the controller may obtain the information in the most differing of ways. In an advantageous embodiment which minimizes errors, the controller is designed to receive information about the number and/or type of identification from identification information containing this information.
In particular, if the device comprises a command input and/or controller, it is advisable to also provide it with a display means for displaying information and/or work steps which will inform the microtomising expert about the number and type of thin slices to be produced and about their associated information. This provides additional control and supplementary inputs.
In a practical embodiment of the device, the detecting means, the supports and the holding means are designed and disposed such that the detecting means can read the identification information from a read field of the support. Towards this end, the support and holding means may be designed and mutually adapted such that the clamping jaws of a holding means designed as clamping means are located outside of the read field of a clamped support. This may be achieved through corresponding arrangement and design of the detecting means or through modification of the clamping jaws compared to the previous clamping devices, wherein the aim is to provide enough space on the read field for a detecting means. The term “read field” means of course that not only optical information but also magnetically or electronically stored information can be read.
The device for preparing identification of object supports through preparing identification information to be associated with the supports can be designed in the most differing of ways. The information carriers may thereby have widely varying designs and the means for generating identification information may also have correspondingly different designs. The means for generating identification information may be designed such that the latter is loaded onto a separate data carrier, wherein this data carrier or a certain data content of a data carrier and the information carrier of the support of the tissue sample are provided with an identification code for mutual cross-reference. This design is particularly advantageous when the sample tissues which are not microtomised and/or microtomised must be associated with a large amount of data and the support is not large enough for mounting a storage medium of sufficient space thereon or when the intended processing of a sample does not accept such a storage medium. In an alternative embodiment, the means and the information carrier are designed such that the entire identification information can be loaded onto the information carrier.
The object supports may obtain different information contents by means of the information distribution key. It is possible to e.g. provide the object supports with different processing instructions for the microtomised tissue samples or the information content of the object support may contain individual evaluation information for the microtomised tissue samples.
Finally, the above-mentioned device can also be used together with the method and the device for carrying out the method in a largely automated fashion. Towards this end, the above-mentioned information content is advantageously designed as device control instructions which can be mechanically read and realized.
For realization, a device for processing microtomised tissue samples disposed on object supports is advantageous which comprises a means for detecting identifications of object supports and a device controller which is designed to realize device controller instructions containing the identifications of the object supports. Such automation which is based on the above-mentioned inventive measures facilitates cross-referencing, in the present case, for further processing.
Further designs and developments are of course feasible, in particular, many method features can be realized as device features and vice versa.