The technical scope of the present invention is that of techniques to produce tissue arrays.
The tissue array is a technique to mount sections of
biological tissues onto microscope slides for their future
5 visual or electronic analysis. The tissue array technique
enables a large number of tissue sections to be mounted onto
the same slide contrary to the technique traditionally
practised in pathology laboratories where only one to three
sections may be mounted together.
10 The tissue array techniques consist in taking one or
several cores from several dozen, or even several hundred, different blocks containing tissue samples either embedded in paraffin or frozen. All the cores are then assembled in a paraffin block or in a frozen inclusion milieu in which 15 recesses have been made.
The tissue array technique is well known and requires no further description here.
Reference may be made, for example, to patent US-6103518 which describes a core sampling device. The embodiment 20 proposed is complicated and based on an arm that is pivoted to successively bring into a working position two sampling punches. The rotation of one punch to the other requires the perfect alignment of the two punches above the core sampling position. Moreover, the position of the donor block support 25 platform must be modified at every operation thereby making the use of such a device both slow and cumbersome.
The aim of the present invention is to supply a core
sampling device that is of simple design, easy to implement
by the user and which overcomes the above drawbacks.
30 The invention thus relates to a core sampling device
intended to assemble tissue arrays of the type incorporating a core excision punch intended to make recesses in one or several so-called receiver blocks, a core sampling punch and means to expel the sample cores into one or several paraffin 35 receiver blocks or into any frozen milieu or not, characterized by the fact that the core excision punch is mounted substantially coaxially in the core sampling punch, the sampling punch being in the external position, both

punches being able to move in translation and/or rotation with respect to one another, and the ejection means being arranged to as to expel the cores from each punch.
According to one characteristic of the invention, the 5 ejection means are positioned in the sampling punch.
According to another characteristic of the invention, the ejection means are in the form of a rod.
According to yet another characteristic of the invention, the external diameter of the rod is close to the internal 10 diameter of the sampling punch.
According to yet another characteristic of the invention, the punches and ejection means are able to move in translation and in rotation independently of one another.
According to yet another characteristic of the invention, 15 the internal diameter of the core excision punch substantially corresponds to the external diameter of the core extracted from the donor block.
According to yet another characteristic of the invention, the sampling punch has an internal diameter that 20 substantially corresponds to the external diameter of the core extracted from the receiver block.
According to yet another characteristic of the invention, the punches have a sharp edge intended to facilitate their penetration into the paraffin or the frozen block as well as 25 to facilitate the extraction of the cores.
According to yet another characteristic of the invention, the device comprises an optical system and a first software interface enabling the core extraction positions to be parametered on a donor block, a second software interface to 30 parameter the core positions on the receiver block or blocks, and a positive identification system for the donor and receiver blocks.
A first advantage of the device according to the
invention lies in the fact that it enables the pathologists
35 to study a large number of patients simultaneously with a
restricted budget and within a limited lapse of time. This
thus enables a great acceleration in the progress of research

knowledge into new prognostic and diagnostic methodologies, and thus into new treatments.
Other characteristics, particulars and advantages of the invention will become more apparent from the description 5 given hereafter by way of illustration and in reference to the drawings, in which:
- Figure 1 shows a schematic view of the device according
to the invention,
- Figure 2 shows an example embodiment of the block
10 support platform, and
Figure 3 shows an example embodiment of a core extraction system.
Figure 1 shows a core extraction device 1 mounted on a support 2 itself integral with a frame 3 fixed onto a support
15 plate 4 intended to support all the elements required for the operation of the device, such as a hydraulic or electrical power unit required to control the different elements, as will be explained hereafter. It classically incorporates a core extraction punch 6 and a core sampling punch 5.
20 According to the invention, these two punches 5 and 6 are
arranged aligned along the same longitudinal axis and defining an inner punch and an outer punch. For the rest of the description, the terms external punch 5 and internal punch 6 will be used. The support 2 receives the external
25 punch 5, the internal punch 6 and an ejector 7. These three parts are mounted aligned along the same axis and able to slide with respect to one another. Punches 5 and 6 are in the form of two tubes, internal punch 6 being inserted in external punch 5. These two punches slide forwards and
30 backwards independently of one another. The ejector 7 is in the form of a solid cylindrical part inserted into the internal punch. Together, these three parts constitute a compact assembly providing all the functionalities of the device 1. Moreover, these three parts are made mobile either
35 manually using toothed bars or by means of the hydraulic unit mentioned previously.
The Figure also shows a support plate 8 on which two core extraction blocks 9 and 10 have been positioned. Block 9 is

constituted, for example, by a sample of tissues from which core samples are to be extracted. This block 9 will be termed donor block. Block 10 is a blank block intended to receive the sample cores taken from different donor blocks. Block 10 5 will be termed receiver block. These two blocks are classically blocks of paraffin or frozen blocks.
Advantageously, the support 2 may be mobile and the block plates immobile, or vice versa.
The core extraction device 1 according to the invention 10 is used in the following manner. Naturally, the device 1 is preferentially used in the vertical position as shown in the plane of the Figure.
Firstly, the ejector 7 and external punch 5 are made to retract so as to partially free the internal punch 6. The 15 receiver block 10 is brought into a precise position using a classical reference guide system. Firstly, a core is removed from the receiver block 10 using the internal punch 6 to provide a recess into which the tissue sample can be inserted. During this phase, the external punch 5 and the 20 ejector 7 are completely retracted, as indicated above.
The internal punch 6 is made to rotate so as to expel the
core taken from the receiver block. This rotation breaks the
base of the core which is then able to be removed without
difficulty. The core is eliminated by sliding the ejector 7
25 into the internal punch 6.
A sample core is then taken from a donor block 9 using the external punch 5 by bringing this block perpendicular to the punches. To do this, the internal punch 6 and the ejector 7 are fully retracted manually towards the support 2 using a 30 toothed bar or automatically using a hydraulic or electric unit. The core sample is removed from the donor block 9 by rotating the external punch 5.
The core sample taken from the donor block 9 is
transferred into the receiver block 10 once this has been
35 brought back into the position initially referenced by making
the recess previously obtained correspond with the position
of the external punch 5. The core sample taken from the donor

block 9 IS then transferred into this recess by sliding the ejector 7 and the internal punch 6 in the external punch 5.
By controlling the height at which the ejector 7 stops, the depth at which the core is introduced into the recess is
5 determined.
This sequence of operations is repeated as often as necessary to obtain the required number of core samples in the receiver block 10 by using different donor blocks 9.
Advantageously, the core extraction device 1 according to
10 the invention is included into an assembly, not shown here, which enables the motorisation of the translational and rotational movements of punches 5 and 6 and of the ejector 7, and of the positioning of the punches above the donor and receiver blocks.
15 This appliance, normally called a tissue arrayer, enables
tissue arrays to be built up from donor blocks embedded in paraffin, or from frozen blocks. In the latter case, the punches are themselves refrigerated to preserve the frozen state of the cores during their extraction and transfer.
20 Its structure may be of the following type.
According to one embodiment, the appliance 1 incorporates a support plate 12 intended to support the donor blocks 9 and a second support plate 12' intended to support the receiver blocks 10. These plates 12 and 12' may be removed from the
25 appliance 1 so as to be loaded up with donor and receiver blocks. The appliance 1 may also incorporate a platform incorporating positioning means for the support plates. This platform may integrate one or several positions for the donor blocks according to the capacity required by the user. Each
30 position incorporates a refrigeration system to keep the donor and receiver blocks frozen during the construction of frozen tissue arrays if using frozen blocks.
The appliance comprises a core extraction device such as that described previously placed on a motor assembly enabling
35 its movement to the nearest micron along the three axes in space so as to place the core extraction system in precise and parametered positions above the donor and receiver blocks. The motorisation also enables the separate rotation

of each punch, as well as the sliding of each punch and of the ejector.
The appliance may also comprise an optical system 13 and
a first software interface 14 enabling the core extraction
5 position or positions to be parametered on the donor block,
and a second software interface 15 to enable the position of
the cores to be parametered on the receiver block or blocks.
The appliance may integrate a positive identification system 16 for the donor and receiver blocks before each core 10 extraction operation (scanning of barcodes, magnetic codes, etc.) to avoid any error.
It may also comprise a system to detect the sample and the length of the cores and associated error management.
Lastly, it may be enclosed in a enclosed space so as to 15 prevent users from interfering with the movements of the sampling system and to protect the samples during these operations and keep them in a dry atmosphere to avoid the formation of condensation and frost on the blocks, the structures and the punches in the case of tissue arrays being 20 constructed from frozen donor blocks.

CLAIMS
1. A core sampling device (1) intended to assemble tissue
arrays of the type incorporating a core sampling punch (5), a
core excision punch (6) intended to make recesses in one or
5 several so-called receiver blocks, and means (7) to expel the sample cores into one or several paraffin receiver blocks (9, 10) or into any frozen milieu or not, characterized by the fact that the core excision punch (6) is mounted substantially coaxially in the core sampling punch (5), the 10 sampling punch being in the external position, both punches (5, 6) being able to move in translation and/or rotation with respect to one another, and the ejection means being arranged to as to expel the cores from each punch.
2. Device according to Claim 1, characterized by the fact
15 that the ejection means (7) are positioned in the internal
punch (6).
3. Device according to Claim 2, characterized by the fact
that the ejection means (7) are in the form of a rod.
4. Device according to Claim 3, characterized by the fact
20 that the external diameter of the rod is close to the
internal diameter of the internal punch (6).
5. Device according to any one of the above Claims,
characterized by the fact that the punches (5, 6) and
ejection means (7) are able to move in translation and in
25 rotation independently of one another.
6. Device according to any one of the above Claims,
characterized by the fact that the internal diameter of the
external punch (5) substantially corresponds to the external
diameter of the core extracted from the donor block (9).
30 7. Device according to any one of the above Claims,
characterized by the fact that the internal punch (6) has an internal diameter that substantially corresponds to the external diameter of the core extracted from the receiver block (10).
35 8. Device according to one of Claims 2 to 7,
characterized by the fact that the punches (5, 6) have a sharp edge intended to facilitate their penetration into the

paraffin or the frozen block as well as to facilitate the extraction of the cores.
9. Device according to any one of the above Claims,
characterized by the fact that it comprises an optical system
5 (13) and a first software interface (14) enabling the core
extraction positions to be parametered on a donor block (9),
a second software interface (15) to parameter the core
positions on the receiver block or blocks (9), and a positive
identification system (16) for the donor (9) and receiver
10 (10) blocks.