Automated sample processing apparatus and a method of automated treating of samples and use of such apparatus

Abstract

An automated staining apparatus and a method for treating samples arranged on a carrier is disclosed, in which portions of two or more selected reagents from a first station containing the reagents are collected individually by a robot arm handling a probe and dispensed in a mixing station of the apparatus. After mixing the reagents in the mixing station, e.g. by shaking or rotating the mixing cup containing the reagents, the reagent mixture is applied to selected samples by the robot arm and a probe.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 60 / 435,601, filed Dec. 20, 2002, hereby incorporated by reference.[0002] This application relates to the field of sample processing systems and methods of processing samples. The present invention may be directed to the automated processing, treatment, or even staining of samples arranged on carriers, such as slides, and in some embodiments, directed to the continuous or batch processing of samples and carriers, as well as washing elements of a sampling system. Embodiments may further relate to control systems for sample processing and data acquisition, data maintenance, and data retrieval for sample processing. Applications to which the present invention may especially relate include immunohistochemistry, in-situ hybridization, fluorescent in-situ hybridization, special staining, and cytology, as well as potentially other chemical and biological applications.[0003] More specifically the present invention...

AI Technical Summary

Benefits of technology

[0043] By providing a staining apparatus having an automated mixer integrated therein, staining or treatment processes requiring a mixture of unmixable reagents, such as a water based and an oil based reagent, or insoluble reagents, can be performed automatically instead of requiring human interaction or manual performance of some process steps in a much more automated process, and the quality of the staining process may be improved as a desired degree of mixing of reagents may be provided or an optimal application time window for a deteriorating mixture may be reached.

[0049] In some staining processes, it is required for one or more treatments to use a mixture of reagents prepared from two or more separate reagents which may be somewhat incompatible e.g. unmixable, such as a water based and an oil based reagent, or insoluble, and therefore requires that the two or more reagents are manually prepared and introduced into a reagent vial shortly before starting the staining process in order to obtain the best possible staining result for the selected examination purposes. For other processes, different staining process steps require a mixture of the same two reagents but in different dissolution ratios. Some process step may require a mixture of two or more reagents that, when mixed, becomes unstable, e.g. has a limited time window of usability because internal chemical processes deteriorates the mixture. By providing a sample processing apparatus having an automated mixer integrated therein, these types of staining processes can be performed automatically instead of requiring human interaction or manual performance of some process steps, thereby achieving a much more automated process, and the quality of the staining process may be improved as a desired degree of mixing of reagents may be provided as well as an optimal application time window for a deteriorating mixture may be reached.

[0064] In order to provide an efficient and fully automated cleansing of the mixing cup when changing from one reagent mixture to the next, it is advantageous that the mixing cup has inner walls extending upwardly and outwardly from a bottom part of the mixing cup, and the cup drive means is capable of rotating the mixing cup at an angular speed sufficient to fling all reagents contained therein out of the mixing cup. Preferably the inner walls are smooth and may terminate in an upper rim at the widest inner diameter of the mixing cup, in which case the high-speed rotation, preferably about a symmetry axis of the cup, will cause the waste reagent or cleansing liquid to be flung out over this upper rim. In an alternative embodiment of the mixer, the inner walls of the cup extend upwards and inwardly above the level of the widest inner diameter, at which one or more exit openings are provided in the inner wall as outlets for the waste reagent or the cleansing liquid. The top may be open for the probe to enter the mixing cup, or it may be closed to facilitate that the cyclic movement of the mixing cup for mixing the reagents may have a vertical component. The probe may in this case enter the mixing cup through one of the exit openings.

[0067] In yet further preferred embodiment, replacing means are provided for replacing the probe that is moved by the probe drive means with another probe, so as to avoid contamination of the reagents in the various reagent vials by the use of more than one probe. This may be combined with a probe washing station, in which one probe is washed after it has been replaced at the probe drive means so that it is clean and ready for repeated use without risking contamination of the content of the reagent vials.

Problems solved by technology

Previously, in some applications, these steps may have been performed manually, potentially creating a time-intensive protocol and necessitating personnel to be actively involved in the sample processing.

However, such previous efforts may have not fully addressed the needs for an automated sample processing system.

Previous efforts to automate sample processing may be deficient in several aspects that prevent more robust automated sample processing, such as: the lack of sufficient computer control and monitoring of sample processing; the lack of information sharing for processing protocol and processing status, especially for individual samples; the lack of diagnostic capabilities; and the lack of real-time or adaptive capabilities for multiple sample batch processing.

Past efforts at automated sample processing for samples presented on carriers such as slides, such as U.S. Pat. No. 6,352,861 to Ventana Medical Systems, Inc. and U.S. Pat. No. 5,839,091 to LabVision Corporation, have not afforded the various advantages and othe

Methods for mixing reagents and liquids are well known--but several aspects are important in the context of IHC and ISH instruments wherein the mixing in some processes can be cumbersome.

The staining procedure is laborious and uses many different reagents.

During the mixing several problems may arise.

Some problems arise due to the complex use of reagents in the staining procedure.

Furthermore, the resulting mixtures are unstable over time and need to be used within a short time.

Many proteins cannot easily tolerate to be exposed to the hydrophobic air in foam.

The foam can spread to other compartments of the instrument in an unwanted and unpredictable way.

Mixing of some reagents like e.g. the HRP chromogens and peroxide reagents can result in the formation of small bobbles.

Some of the reagents or buffers are incompatible with each other's.

In the event of cross contamination due to e.g. carry over, the reagents may be ruined within seconds or solids can precipitate, making the staining unsuccessful.

For example, enzyme containing reagents can not be mixed with the corresponding chromogens, or high salt concentrates may not be mixed with e.g. proteins containing mixtures, or organic solvents can not be mixed with protein containing mixtures, or highly pH buffered wash buffers can not be mixed with low buffered mixtures without significantly altering the properties of the reagents.

As the procedures are very complex, and the instrument uses many different protocols, one cannot predict the result of reagent carry-over or unplanned mixing of reagents.

Build-up of small fouling layers on the surfaces will fast cause problems, as the typical staining protocol calls for many mixing and dilution steps.

On the slide mixing does not allow for very large ratios of dilution.

Nor does it allow for efficient mixing of reagents with very different densities or viscosity.

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