This invention relates to staining systems for slide-mounted specimens for example for immunostaining. By "staining", however, is meant any procedure for treating specimens whether it involves a change of colour or otherwise.

Conventionally, staining is performed on specimens using different reagents and different procedures according to the specimen and the end result required. By and large this is done by manual application of reagents according to predetermined routines but automated instruments are available which can be loaded with appropriate reagents in carousel or like arrangements and which are programmable to apply the reagent to the slides in the correct sequence and for the requisite periods of time.

The staining procedures are currently undergoing simplification inasmuch as so-called EPOS reagents comprising antibodies linked to a polymer support carrying multiple enzyme molecules are now available which carry out in one step procedures which have previously involved multiple applications.

In any event, the available automated instruments are complicated and expensive and require programming

for different processes without being really adapted to many operational requirements. Some, for example, will process multiple specimens, but only if all specimens are subject to identical procedures. Available systems which can simultaneously process different specimens with different routines require all slides to be mounted and the appropriate programs and reagents loaded before processing begins and, once set in operation, slides cannot be inserted or removed or procedures or reagents changed.

The present invention provides an improved staining system which does not suffer the disadvantages of existing such systems and which is particularly adapted (but not limited) to the use of EPOS reagents.

The invention comprises a staining system for slide-mounted specimens comprising first support means for treatment medium applicator means and second support means for slides and drive means for relative movement between slides on said second support means and applicator means on said first support means and control means associated with slides on said second support means controlling said applicator means .

Said second support means may comprise a track along which slides are moved past said applicator

means. Said track may comprise a runway for slide carriers and the system comprise means moving said slide carriers along said runway. The track may be rectilinear.

Said applicator means may be comprised at a plurality of applicator stations for treatment media spaced apart along said first support means in the direction of relative movement. The applicator stations may be spaced apart by distances depending on the treatment times required for treatment by the treatment media they apply.

Said applicator means may comprise applicators for different treatment media selected by said control means and may comprise carousel means holding a plurality of different treatment media and indexable by said control means to bring the appropriate treatment medium into position relative to a slide for application.

Said control means may comprise read means reading indicia associated with said slides and coding for the treatment required. Said indicia may comprise bar code and said read means may comprise then bar code read means.

The system may have a plurality of applicator positions on said first support means and read means at

each position selecting an applicator of applicator means at such position. The system may, however, have a plurality of applicator means on said first support means and read means at one initial position on said first support means selecting an applicator of applicator means at each position.

The system may comprise a plurality of applicator means spaced apart along said first support means and intermediate wash station means. Said wash station means may comprise slide tilting means tilting slides being treated for drainage.

The system may comprise a sump for waste reagents, and may also comprise a temperature control arrangement which may be adapted to maintain a constant temperature of the said second support means.

The system may be adapted as an immunostaining system.

The invention also comprises a method for staining specimens on a plurality of slides with different reagents comprising subjecting each slide to an appropriate reagent for a given time which is the same for all the slides and all the reagents and selecting the concentrations of the reagents so as to

complete its treatment of the specimen to which it is applied in said given time.

Embodiments of staining systems and methods according to the invention will now be described with reference to the accompanying drawings, in which :-

Figure 1 is a diagrammatic perspective view of one system;

Figure 2 is a simplified section through a system according to Figure 1 showing more details;

Figure 3 is a plan view of a slide, bearing control indicia and specimen;

Figure 4 is a diagrammatic elevation of a wash station of the system illustrated in Figure 1.

The staining system illustrated in the drawings for slide (12) mounted specimens 11 (Figure 3) comprises first support means 13 for treatment medium applicator means 14 and second support means 15 for slides 12 and drive means 16 for relative movement between slides 12 on said second support means 15 and applicator means

14a,14b,14c,14d on said first support means 13 and control means 17,18 associated with slides 12 on said second support means 15 controlling said applicator means.

Said second support means 15 comprise a track along which slides 12 are moved past said applicator means 14 and said track comprises a runway for slide carriers 19 and the system comprises means 21 in the form of endless belts or chains moving said slide carriers 19 along said runway. The belts or chains are driven by electric motor means 22. The track is rectilinear so that the slides are introduced to the system at one end 15a of the track support means 15 and are removed at the other end 15b. Introduction and removal may be effected manually, of course, it being only necessary to drop the slide 12 on to a slide carrier 19 on the track 15 and pick it off at the other end, but automatic loading and preferably unloading arrangements may be utilised avoiding the need to stand by the arrangement for unloading processed slides.

Said applicator means 14 are comprised at a plurality of applicator stations 23 for treatment media spaced apart along said first support means 13 in the direction of said relative movement, i.e. along the track 15. The applicator stations 23 are spaced apart

by distances depending on the treatment times required for treatment by the treatment media they apply. As illustrated, essentially for use with EPOS systems, there are four such applicator stations 23a, 23b, 23c and 23d, stations 23a and 23b being for the application of first and second pretreatment media, station 23c being the EPOS applicator station and station 23d being for the application of a chromagen. As will be seen, the first and second pretreatment stages are fractions of the length of the EPOS treatment stage of which the chromagen stage length is also a fraction. As the slides 12 move at a constant speed, the treatment times will be proportional to the stage lengths.

The rate of slide travel may be such as to spend say twenty minutes traversing the EPOS stage.

Said applicator means 14a,14b,14c,14d comprise applicators 14 for different treatment media selected by said control means 17,18. Said applicator means 14a, 14b,14c,14d each comprise carousel means holding a plurality of different treatment media and indexable by said control means 17,18 to bring the appropriate treatment medium into position relative to a slide 12 for application.

As better seen in Figure 2, the carousel means 14c there depicted has locations around its periphery

supporting hoppers 31 for reagents with electronically operated valves 32 and delivery tubes 33 directing reagent on to the specimen 11.

The control means 17,18 comprise read means 17a reading indicia 18 associated with the slides 12 and coding for the treatment required. The indicia 18 comprise bar code and the read means 17a comprise bar code read means. There are four carousels, each with an associated bar code reader 17a each reading one of four tracks of bar code 18 appropriate to control the associated carousel. The EPOS carousel at applicator station 23c is a "maxi" carousel holding (as illustrated) twenty (but could be more or less) reagent hoppers while the pretreatment and chromagen carousels at stations 23a, 23b and 23d are "mini" carousels holding just a few different pretreatment and chromagen media, but the precise arrangement will naturally depend upon the purpose for which the instrument is designed.

Instead of separate read means 17a for each applicator station, the first-encountered such read means may read all of the information in the bar code into a master controller for distribution at the appropriate times to the appropriate stations.

The bar codes may contain information not only about which reagent to select at which carousel but also

about how much to apply, or, perhaps taking viscosity into account, how long to keep the valves 32 open to deliver specified amounts of the different reagents.

Intermediate the applicator stations 23a, 23b, 23c and 23d are wash stations 34 (whose position only is illustrated in Figure 1) at which buffer solution is applied to the slide to wash away the previously- applied reagent. Each wash station, as illustrated in Figure 4, has a ramp 35 on which the slide 12 is tilted while buffer is applied from a dispenser 36, the tilt allowing the buffer to run off into the sump 38 (see Figure 2) in which waste reagents washed off by the buffer solutions are collected. After the ramp 35 is an oppositely, but lesser, inclined ramp 37 which permits any buffer not shed at the ramp 35 to drain (through perforations 38 in the runway 15) before the next- encountered applicator station.

The timing is such that specimens are not allowed to dry out between applicator and wash stations.

A thermostat controls a heater in the second support means 15 so as to maintain the slides for example at 37°C for optimum effect. A humidity control system (which may simply comprise hinged covers permitting access to the various parts of the arrangement) may be fitted to prevent any tendency of the slides to dry out.

Typically, the dwell time for a slide in the EPOS applicator stage will be 20 minutes, total processing time being typically 60 minutes. More than one slide, of course, can be accommodated in each stage and slides can be loaded at the rate, say, of one every two minutes or so, giving a possible processing rate of 25-30 slides per hour.

Unlike currently available automatic immuno- staining instruments, however, the system can be operated on a continuous, rather than a batch throughput basis and slides loaded on an "as received" basis up to the maximum throughput capacity of the system with no requirement to keep the system fully loaded. "Emergency" slides can simply be loaded out of turn with no reprogramming requirement.

With currently available systems, different reagents are applied for different purposes for periods of time (usually specified by the reagent supplier) and the control of treatment time is therefore a requirement of such systems. According to the present invention, reagents are "tailored", for example by selecting their concentrations, to complete their treatments in a given time which is the same for all the reagents used in the system.

The system is capable of adaptation and modification to meet different requirements. While a straight-line runway is clearly convenient, the track could be curved and even circular. To reduce the "footprint" of the system, the track could be arranged on a vertical "tower" basis.

The bar codes (or magnetic or other machine readable codes or characters) can be supplied on adhesive tabs to be secured on the frosted end of a conventional microscope slide (no special slides are required by the system) by the pathologist or laboratory worker requesting the staining procedure, the tabs also, of course, carrying a visual indication of the procedure. Reagents would of course need to be appropriately loaded into the carousels but to avoid errors through incorrect loading, each reagent hopper might be supplied ready filled by the manufacturer and have a code (like photographic film speed codes) that activated a sensor in the carousel identifying to the master controller the position in the carousel of the reagent. Then, if a bar code called for a missing reagent, the system would raise an alarm. Alarm could also be raised by hopper level detectors indicating the need to replace an empty hopper.

The bar code or other reading arrangement can, prior to taking any action in regard to the slide, print out a resume of the instructions coded for, so that a check can be made to see that the instructions are appropriate.