WO2014001530A1

WO2014001530A1 - An automated staining apparatus comprising cooled drawers for reagent bottles

Info

Publication number: WO2014001530A1
Application number: PCT/EP2013/063688
Authority: WO
Inventors: Lars Winther
Original assignee: Victorious Medical Systems Aps
Priority date: 2012-06-29
Filing date: 2013-06-28
Publication date: 2014-01-03

Abstract

An automated apparatus for staining of biological samples arranged on slides comprises a reagent bay section for holding a plurality of reagent bottles, an optical reader for reading bottle labels, and an automated reagent dispensing system. The reagent bay section comprises at least two drawers, each of which is slidably received in a drawer section of the staining apparatus, each of the drawers being individually movable by rectilinear translational sliding movement between an open and a closed state. A cooling system is provided for maintaining an interior section of each of the drawers at a temperature below 12°C, such as between 2°C and 8°C. The bottles are held in a matrix configuration within the drawers, and each one of the drawers is configured to hold bottles of at least two different sizes or shapes.

Description

AN AUTOMATED STAINING APPARATUS COMPRISING COOLED DRAWERS FOR REAGENT BOTTLES

Technical field

The present invention relates to an automated staining apparatus for staining of biological samples arranged on slides, notably to improvements of a reagent bottle bay section thereof.

Background of the invention

Current state of the art apparatus for staining of biological samples arranged on slides generally fall in two categories.

In a first category of stainers, the reagents are stored at ambient temperature in closed containers with built-in dispenser and are organized in a carrousel with a label reader at a fixed position. Reagents are dispensed directly onto slides organized in carousels below the reagent carousel. Alternatively, ambient temperature reagent containers with build in dispenser are organized in an array and physically moved by a robot arm to a position over slides organized in arrays. A label reader is placed in the robot head.

In a second, alternative category of stainers, a so-called array design is provided with reagent bottles and slides organized in rows, the design comprising drawers and an overhead robot incorporating a sip and spit reagent probe and a label reader. In the above designs, all the reagents are stored at ambient temperature, and handling of reagents can cause disturbance of the stainer's operation.

One commercially available stainer, Biocare intellipath FLX, incorporates two cold spots for intermediate storing of mixed chromogens but stores all the reagents at ambient

temperature.

On this background, it is a general object of embodiments of the present invention to provide a stainer (i.e. a staining apparatus), which:

requires few hands-on operations only,

- provides an easy way of loading and offloading reagent bottles,

can be operated without long waiting times,

allows continuous loading and offloading of reagents at any convenient time without interrupting operation of the apparatus,

can accommodate sufficient reagents for a full workday and/or overnight runs, is flexible to allow for unplanned protocol changes.

More specifically, embodiments of the present invention seek to solve at least some of the following technical problems:

- Managing of a large number of different reagents.

Managing of differently sized reagent bottles, from less than 1 ml, 2, 5 and up to 25, 50 or 250 ml.

Allowing reagent handling during operations of the staining apparatus.

Allowing loading of reagent bottles at any time.

- Ensuring sufficient shelf life of the reagent bottles once accommodated within the staining apparatus.

Enabling fast reading of bottle labels.

Providing a compact design of the reagent loading system.

Reducing costs and energy consumption.

- Providing a reliable and safe design.

Reducing noise.

Summary of the invention The present invention provides an automated staining apparatus for staining of biological samples arranged on slides, comprising

a reagent bay section for holding a plurality of reagent bottles;

at least one optical reader for reading information provided on the surfaces of said bottles for identifying the contents of the respective bottles;

- an automated reagent dispensing system for receiving controlled amounts of reagent liquid from the bottles and for dispensing said amounts of reagent liquid onto the slides; an electronic control system operatively associated with the optical reader and said dispensing system, so as to control operation of the reader and of the dispensing system; wherein:

- the reagent bay section comprises at least two drawers, each of which is slidably received in a drawer section of the staining apparatus, the drawers and the drawer section being configured to allow each of the drawers to be individually moved by rectilinear translational sliding movement between an open state, in which an interior section of the drawer can be accessed by a user for insertion and removal of the bottles, and a closed state, in which the interior section of the drawer is fully received in the drawer section of the staining apparatus, and in which the interior section of the drawer is accessible by the dispensing system only; - the apparatus comprises a cooling system for maintaining the interior section of each of the drawers at a temperature below 12°C, such as between 2°C and 8°C, when the drawer is in the closed state;

each of the drawers is configured to hold the reagent bottles in a matrix configuration; - each one of the drawers is further configured to hold bottles of at least two different sizes, shapes or volumes.

The combination of cooled drawers, a plurality of independent drawers and the matrix configuration of the bottle-holding structure of the drawers along with the ability to hold bottles of different sizes or shapes results in a number of benefits. The design is compact, and hence a large number of different reagents can be managed by the apparatus and differently sized reagent bottles can be handled. The ability to individually and independently open and close the drawers allows reagents to be handled during operation of the staining apparatus and loading of reagent bottles at any time. The optical reader is preferably arranged in a section of the apparatus, which constitutes a frame structure for the drawers. For example, the optical reader may be integrated in or mounted to the frame structure for the drawers. Accordingly, in preferred embodiments of the invention, reagent bottle labels may be read independently from staining operations carried out by the apparatus, because the optical reader is not structurally integrated with the dispensing system or other elements used during staining. The labels of the reagent bottles may thus be read when the drawers are being closed, and an operator of the apparatus may in turn be immediately alerted if an error or malfunction occurs. Other operations, such as baking, dewaxing, target retrieval and staining preferably occur independently from the reading of bottle lables. The apparatus is preferably configured such that the drawers may be opened and closed independently from one another. For example, one drawer may be opened while another drawer is open, and/or while reagents are being mixed in another drawer. The apparatus is preferably also configured such that staining operations may take place, while one or more drawers are open.

The cooling system extends the shelf life of the reagents once the bottles are loaded into the apparatus, and hence the compact design allowing for a large number of bottles to be accommodated within the apparatus can be exploited to a maximum degree. The slides may include biological samples arranged or mounted on the slides, such as more specifically, cell smears or cells mounted on microscope glass. More specifically, the invention is applicable with regard to immunohistochemistry (IHC), special stains (SS) or in-situ hydridzation (ISH) staining of FFPE tissue sections mounted on microscope glass slides. The matrix configuration may be a rectilinear matrix configuration with bottles held in rows and columns, or an arcuate configuration, such as a circular, half-circular, oval or half-oval configuration. The matrix of bottles is preferably a two-dimensional matrix coinciding with or extending parallel to with the plane, in which each of the drawers undertake the translational sliding movement between the open and closed positions.

The invention also provides a system comprising an automated staining apparatus according to any of the preceding claims and a plurality of said reagent bottles, wherein the bottles and the interior section of the drawers are polar to prevent incorrect placement and positioning of the bottles within the drawers.

The control system and the dispensing system may be configured to withdraw amounts of liquid from bottles from a first one of the drawers, while a second one of the drawers is in its open state.

The at least one optical reader may securely fixed to the drawer section of the staining apparatus at a position, in which said bottle information passes the reader, while the drawers close, so as to enable the reader to read the information, while the drawers undertake said rectilinear sliding movement between the open and the closed state.

The at least one optical reader may be releasably attachable to a plurality of positions at the drawer section of the staining apparatus, in which said bottle information of respective sets of drawers pass the reader, while the drawers undertake said rectilinear sliding movement between the open and the closed state. For example, a port structure may be provided, which is releasbly attached at the drawer section of the staining apparatus, the port section comprising the at least one optical reader. The port structure may be movable, so as to be attachable at a plurality of drawer sites at the drawer section.

The at least one optical reader may comprise two or more optical readers arranged at respective sides of each drawer for reading information from bottles arranged at respective sides of the drawer.

The at least one optical reader may be securely fixed or attachable to the drawer section of the staining apparatus at a position between two neighbouring ones of the drawers, so as to enable one single optical reader to read information on bottles in the neighbouring drawers. The information may be provided in barcodes printed onto the bottles or printed on labels attached to the bottles. The at least one optical reader may be arranged in a non-cooled section of the drawer section.

The automated staining apparatus may further comprising robotics, control electronics and fluidics tubes, in which case said robotics, control electronics and fluidics tubes are preferably arranged in a non-cooled section of the staining apparatus.

The control system may be configured to determine if the bottles are correctly placed within the drawer and to generate an error or warning signal in the event of incorrect placement.

In one embodiment of the automated staining apparatus according invention:

each of the drawers comprises an insulating front section;

- the interior section of each drawer is covered by an insulating lid assembly at least in the closed state of the drawer, the dispensing system being configured to access the bottles through apertures in the lid; and wherein

- the drawer section of the staining apparatus, said front section and said lid assembly are configured to provide an essentially closed compartment in the closed state of the drawer. The insulating lid assembly may comprise a plurality of overlapping perforated plates arranged to be mutually slidable between an access state, in which perforations of the plates co-extend to provide access to the bottles in the interior section of the drawer, and a non- access state, in which the perforations do not co-extend, whereby the plates provide a closed lid of the drawer.

Each of the drawers may comprise a removable tray insert for receiving the bottles.

The dispensing system may comprise a pipette or probe for withdrawing controlled amounts of reagent liquid from the bottles and optionally further a heating element for heating the pipette.

In the system according to the invention, the bottles may comprise a bundle of bottles with only set of information thereon for identifying the contents of all of the bottles of the bundle. Detailed description of the invention

The invention will now be further described with reference to the accompanying drawings, in which: Figs. 1 - 3 are simplified sketches of embodiments of an automated staining apparatus according to the present invention;

Fig. 4 is a simplified drawing of an embodiment of an automated staining apparatus according to the invention;

Figs. 5 - 7 illustrate details of a drawer for an embodiment of an automated staining apparatus according to the invention;

Fig. 8 depicts various reagent bottles and inserts.

Preferred embodiment of the present invention come as a result of several logical design circles:

In order to store sensitive biological reagents like diluted antibodies, probes, enzyme containing visualization systems, or chemically labile chromogens or counterstains, for a long time and with semi open bottles for ease of automatic instrument operations, all the reagents should be stored at cold conditions, preferably at 2-8°C.

The inventor has realized that introduction of a general cold storage for many different reagents in different volumes in combination with user-friendly reagent handling and a reliable and cost efficient instrument operation requires a fundamental redesign, compared to state of the art stainers.

Specifically, the inventor has realized that in order to efficiently store reagents in the cold, the cooled volume should be reduced to a minimum. The reagent bay should be both compact and easy to isolate thermally. Therefore, a matrix design with reagent bottles and an indirect sip and spit dispensing pipette design is preferable due to the compactness, ease of modification for different bottle sizes and low cost. Also, in order to efficiently use reagents extracted from a cold storage in the tissue staining process, it is preferable to heat up the reagent in the pipette while the robot arms move the reagent from the storage to the staining section, where they are dispensed in the drop zone.

In order to reduce the operator ^'s general stress of handling reagents at scheduled time intervals, it should be possible to load reagents at virtually any time while at the same time minimize any disturbance in the stainer operation. The inventor has realized that the reagent bottles should be organized in several independent sections and preferably in several independent drawers.

Thereby the instrument can extract reagents from bottles in the other drawers, while one drawer is open and being manipulated by the operator.

Also, as the entire cooled storage compartment is not opened and only subset of the reagents are pulled out of the instrument during loading this efficiently helps to keep the cold reagent temperature. Again in order to have a temperature-stable, efficiently cooled, and compact storage compartment for reagents, any bulky robotics with sensitive mechanics, electronics and fluidics lines should be kept outside the cooled area. Access to the reagents in the cooled storage room should therefore be through small ports in the lid. In one embodiment, this is achieved by a flat and isolated lid assembly consisting of two plates with small holes. By sliding one of the plates, the holes can automatically be opened or closed.

Further, as the loading should be independent of the instrument ^' s operation, the optical label reader should be independent of the rest of the instrument ^'s operation - i.e. not on the reagent robot head.

The inventor has realized that optical readers preferably should not be placed in the cold storage with the reagents, as relatively moist air sipping in from the outside during opening of the storage area could result in water condensation on the optical lenses and cause critical malfunction.

A heated optical lens system could reduce this problem but this would work against the efficiency of the cold storage area.

To solve this problem, a preferable design is a set of optical readers at the drawers port and outside the cold area, (as illustrated in Fig. 5).

Preferably the readers are static while reading the passing bottle information while the drawer closes. As only one drawer is to be closed at a time, to save cost, the same set of readers can be re-used for several drawers, and automatically be moved between the drawers ^' ports. Also, the inventor has realized that reading the reagent bottle information while the drawer is closing is both an efficient and practical method. Especially, as the operator can immediately get feed back from the reader's software and database on whether the reagents are correctly loaded into the drawer.

Lastly, the inventor has concluded that in order to harbour many different types and sizes of bottles in the drawers, it is preferable to use various inserts in the drawer. Thereby new bottle size configurations can be implemented safely, easily and cost efficiently. Also, physical bundles of reagent bottles (e.g. Ready-to-use antibody or molecular probe panels, entire visualizations systems, chromogen systems or antibody concentrates with bottles containing diluents) can be loaded together with only one label and even occupying positions between the standard rows in the drawer. This will increase the reagent capacity and density in the drawer.

This combination of design elements addresses all the general user care-abouts.

The reagent drawer, loading and handling features in more detail :

The compartment consists of three individual drawers, each holding 2 (or 4) rows of up to 19 reagent bottles or containers

The storage compartment is cooled by peltier elements to 2-8°C

The storage compartment is thermally isolated from the rest of the stainer

- The sip and spit reagent probe has access to the individual bottles through holes in the top lid which can be opened and closed

The isolated lid consists of two plates with holes. By sliding one of the plates a short distance, all holes can be closed or opened

The optical label readers are placed on each side of the drawer

- When drawers are closed, the pair of optical readers will automatically be moved to the next drawer to be read from

The optical readers are placed outside the cold compartment, to avoid condensation of water on the lenses

The sip and spit pipette can extract reagents from the other drawers while one drawer is open

The position of reagent bottles to be manipulated by the operator in the drawer are optionally marked with small LED diodes for easy location

The reagents sit in a drawer insert with polar parking locations

The reagent bottles are polar in design Differently sized bottles will fit into the drawer insert using plastic inserts

When placed in the drawer, the bottles are uncapped and only closed with e.g. "a split membrane closure"

The bottle labels are in the same plane in the drawer

The labels can be read from the side and slightly above and are all facing to the side of the drawer

The sip and spit reagent pipette is heated

Some bottles are loaded with only one chromogen component and used for mixtures of chromogens, which are discarded after use

Some bottles are loaded empty and used for dilutions

Some bottles loaded can be prefilled with a dilution buffer and used for dilution series of e.g. antibodies or for automatic preparation of antibody solutions from concentrates If only a few reagents, e.g. a rare primary antibody, is to be loaded, the drawer is only partly opened to make room for the bottle change. This is in order to reduce the response time

A package, bundle or kit of several bottles can be loaded into the drawer as a single physical entity and with only one bar code. Thereby, the positions between the two rows can be filled with extra bottles. This is an upgrade feature, which only needs an updated lid and new drawer inserts.

Typical operation procedure of the invention:

Reagent bottle loading or offloading :

1. The reagent change function is chosen in the software user interface

2. The drawer is selected by operator or software

3. The operator is informed that the drawer is ready to be opened within seconds

4. The optical label readers are automatically moved to the drawer to be opened

5. The drawer opens automatically

6. Small diode lights in the drawer mark change suggestions for the individual bottles or positions

7. The operator loads and/or removes the bottles manually

8. The operator prompts the instrument to close the drawer

9. The drawer closes automatically, while the labels are read

10. The ID is read and the software performance an inventory check and update with the database

11. If O.K., the operator gets an accept receipt

12. If not O.K., the operator gets an error/correction message and the drawer is opened again for correction. 13. Optionally, steps 4 to 11 are repeated for the next drawer Reagent sip and spit operation:

1. When the drawer holding the particular reagent is closed

2. The sip and spit pipette is moved to a position over the selected reagent bottle

3. The holes on the lid opened by shifting one part of the plate

4. The pipette is lowered through the hole and into the particular bottle

5. An amount of reagent withdrawn ("sip") into the heated pipette

6. The pipette is lifted up

7. The holes on the lid are closed

8. The pipette robot arm moved to the staining module over a particular drop channel and lowered

9. An amount of reagent dispensed ("spit") into the drop channel

10. Optionally, the dispensing is repeated in several drop channels

11. The pipette is moved to the washing station and cleaned inside and outside

12. The pipette robot arm is moved to a resting position

Chromogen mixture:

1. When the drawer holding the particular reagents is closed

3. The holes on the lid are opened

4. The pipette is lowered through a hole and into the particular bottle with e.g. chromogen concentrate

5. An amount of reagent (e.g. 150 micro liter) is drawn (sipped) into the pipette

6. The pipette is lifted up

7. The pipette is lowered through a hole and into another bottle with e.g. chromogen buffer substrate (e.g. 5 ml)

8. The reagent is dispensed into the bottle

9. The pipette is moved slightly up or down

10. An amount of reagent mixture (e.g. 1500 micro liter) is drawn (sipped) into the pipette, the pipette is moved slightly up or down and the reagent mixture is immediately spit out again into the bottle.

11. Step 10 is repeated several times to promote mixing of the components

12. The pipette is lifted up

13. The holes on the lid are closed

14. The pipette is moved to the washing station and cleaned inside and outside General performance advantages:

RTU reagents, concentrates and mixed chromogens can be stored for prolonged periods. Even semi open bottles can be stored, without risk of evaporation Delicate chromogen mixtures can be made automatically and stored for prolonged time

Label readers mounted at the drawers

o The dispenser robotics is independent of the reagent loading/label reading and eliminates any scheduler problems and makes the instrument faster and more flexible

o The label reader is protected from condensing water

o Two readers can cover several drawers, which reduces the cost

Labels read while drawer is closed

o Fast loading and reagent registration

o Label or reagent errors or misplaced reagent bottles will be detected fast - and while the operator is still next to the instrument.

Compact design and many reagent bottles

o Small foot print compared to capacity

o Large number (+ 100) of reagents is important in the IHC procedures

o It is not necessary to remove empty bottles at once

Several independent drawers

o The reagents can be loaded at virtually any time and when most convenient for the operator

Figure 1 shows a simplified sketch of an embodiment of an automated staining apparatus with a functional skin, including touch screen (15.1), drawer for slide rack (15.2), three drawers for specific reagent containers (15.3), doors for access to bulk reagents (15.4) and waste containers (15.5) and a pull out table (15.6).

Figure 2 is a simplified sketch of an embodiment of an automated staining apparatus with a functional skin seen from the front and side, including a 170 cm tall reference person, including touch screen (16.1), pulled out drawer for slide rack (16.2) and specific reagents. Figure 3 is a sketch of an embodiment of an automated staining apparatus with a functional skin. To the left with open door to the bulk reagents (17.1) and to the right with the top lid open for access to the robotics during repair and service (17.2).

As schematically illustrated in figure 4, an embodiment of an automated staining apparatus comprises several treatment modules and robots, including a drawer (6.1) for loading and off loading racks, an overhead gantry robot (6.2) that can grab, lift, transport, lower and release slide racks into the various positions in the apparatus, a storage room (6.3) for multiple slide racks, a warm air baking and drying module (6.4) harboring more than one slide rack, a dewaxing and rehydration module (6.5), a target retrieval module (6.6) with an array of target retrieval dip tanks, a staining module (6.7) with mixing grid, an overhead x-y-z reagent delivery robot (6.8) with a multidispensing reagent probe and air knife, a reagent bay or module (6.9) harboring multiple specific reagent containers under temperature control and accessible for loading and changing through separate drawers (6.10) .

The lower part of the staining apparatus comprises a number of bulk reagent containers (6.11) for wash and target retrieval buffer concentrates, dewaxing, rehydration and dehydration solutions, in addition to waste containers for organic (6.12) and toxic aqueous waste (6.13) and an internal water purification module (6.14) capable of purifying tap water for use in the apparatus. The apparatus has a connection to the general sewage system for the non-toxic aqueous waste. The apparatus has a supporting and stable frame (6.15) mounted with wheels (6.16).

The apparatus can store and process several slide racks at the same time. The gantry robot moves the racks between the treatment, storage and loading modules.

Figure 5 shows a detail of a reagent bay including a drawer for holding reagent bottles. The reagent bay holds the multiple reagent bottles under cooled (2-8°C) and controlled conditions. When prompted by the operator, one of the three drawers is automatically opened and the operator can load, change or remove the reagent bottles. The individual reagent bottles of different sizes are securely placed in a reagent drawer tray insert (101). When the drawer slowly closes again, the machine readable labels (102) on the reagent bottles pass a pair of optical readers on each side of the drawer (103) which register the bottle labels. The stainer uses only two optical readers in the reagent bay, which can be moved from drawer to drawer on a rail. They are placed outside the cooled area to prevent condensation problems on the lenses when the drawer is open. When closed, the reagent drawer front (104), sides and top lid (105) form an isolated compartment Figure 6 shows the reagent drawer of Fig. 5 in more detail. Before opening the next drawer, the optical label readers are moved in position to read the labels from each side (103) . When the drawer is open, the insert can be removed and the drawer emptied in one operation (101). The independent drawer design allows for both flexible and nearly continuous reagent loading, while the stainer is operating. While one drawer is open, the reagent probe or pipette can still sip and spit reagents from bottles in the other drawers (106), here made visible with the lid removed.

Figure 7 shows the reagent drawer of Figs. 5 and 6 and a reagent tray insert 107. The drawer tray insert holds the differently sized reagent bottles and containers and is polar, which prevents wrong placement and positioning of the reagent bottles. The drawer insert (107) also facilitates removal of the entire content of a drawer in one simple operation.

Fig. 8 shows various reagent bottles and inserts for the apparatus and system according to the present invention. The drawer is designed to hold many differently sized bottles in flexible configurations by means of inserts and bottles which fit together. For example, 50, 15, 5 and 2 ml bottles have the same height and opening mouth and placement of machine readable label. The polar inserts allow the 15, 5 or 2 ml bottles to safely fit in the larger 50 ml bottle space in the reagent drawer for maximum loading and positioning flexibility. The smaller bottles can be inserted as single or double configuration in each insert. Bottles containing 50, 15, 5 and 2 ml (14.1, 14.2, 14.3, 14.4) and the corresponding insert (14.5) for the 15 and 5 ml bottles (14.2, 14.3) may occupy the space of a 50 ml bottle and the insert (14.6) for one or two 2 ml bottles (14.4).

Claims

1. An automated staining apparatus for staining of biological samples arranged on slides, comprising

- a reagent bay section for holding a plurality of reagent bottles;

an automated reagent dispensing system for receiving controlled amounts of reagent liquid from the bottles and for dispensing said amounts of reagent liquid onto the slides; - an electronic control system operatively associated with the optical reader and said

dispensing system, so as to control operation of the reader and of the dispensing system; wherein:

- the reagent bay section comprises at least two drawers, each of which is slidably received in a drawer section of the staining apparatus, the drawers and the drawer section being configured to allow each of the drawers to be individually moved by rectilinear translational sliding movement between an open state, in which an interior section of the drawer can be accessed by a user for insertion and removal of the bottles, and a closed state, in which the interior section of the drawer is fully received in the drawer section of the staining apparatus, and in which the interior section of the drawer is accessible by the dispensing system only;

- the apparatus comprises a cooling system for maintaining the interior section of each of the drawers at a temperature below 12°C, such as between 2°C and 8°C, when the drawer is in the closed state;

2. An automated staining apparatus according to claim 1, wherein the control system and the dispensing system are configured to receive amounts of liquid from bottles from a first one of the drawers, while a second one of the drawers is in its open state.

3. An automated staining apparatus according to claim 1 or 2, wherein the at least one optical reader is securely fixed to the drawer section of the staining apparatus at a position, in which said bottle information passes the reader, while the drawers close, so as to enable the reader to read the information, while the drawers undertake said rectilinear sliding movement between the open and the closed state.

4. An automated staining apparatus according to claim 1 or 2, wherein the at least one optical reader is releasably attachable to a plurality of positions at the drawer section of the staining apparatus, in which said bottle information of respective sets of drawers pass the reader, while the drawers undertake said rectilinear sliding movement between the open and the closed state.

5. An automated staining apparatus according to claim 3 or 4, wherein the at least one optical reader is securely fixed or attachable to the drawer section of the staining apparatus at a position between two neighbouring ones of the drawers, so as to enable one single optical reader to read information on bottles in the neighbouring drawers.

6. An automated staining apparatus according to any of the preceding claims, wherein the at least one optical reader is arranged in a non-cooled section of the drawer section.

7. An automated staining apparatus according to any of the preceding claims, further comprising robotics, control electronics and fluidics tubes, and wherein said robotics, control electronics and fluidics tubes are arranged in a non-cooled section of the staining apparatus.

8. An automated staining apparatus according to any of the preceding claims, wherein the control system is configured to determine if the bottles are correctly placed within the drawer and to generate an error or warning signal in the event of incorrect placement.

9. An automated staining apparatus according to any of the preceding claims, wherein:

each of the drawers comprises an insulating front section;

- the drawer section of the staining apparatus, said front section and said lid assembly are configured to provide an essentially closed compartment in the closed state of the drawer.

10. An automated staining apparatus according to claim 9, wherein the insulating lid assembly comprises a plurality of overlapping perforated plates arranged to be mutually slidable between an access state, in which perforations of the plates co-extend to provide access to the bottles in the interior section of the drawer, and a non-access state, in which the perforations do not co-extend, whereby the plates provide a closed lid of the drawer.

11. An automated staining apparatus according to any of the preceding claims, wherein each of the drawers comprises a removable tray insert for receiving the bottles.

12. An automated staining apparatus according to any of the preceding claims, wherein the dispensing system comprises a pipette for receiving controlled amounts of reagent liquid from the bottles and a heating element for heating the pipette.

13. A system comprising an automated staining apparatus according to any of the preceding claims and a plurality of said reagent bottles, wherein the bottles and the interior section of the drawers are polar to prevent incorrect placement and positioning of the bottles within the drawers.

14. A system according to claim 13, wherein the bottles comprises a bundle of bottles with only set of information thereon for identifying the contents of all of the bottles of the bundle.