NZ575341A - A hand held tissue sampling device having a rotatable punch holder holding a plurality of punches - Google Patents

Abstract

An applicator for sampling tissue is disclosed. The applicator includes a punch drive section including an applicator punch, which operates along a first axis, means for retaining a punch holder, and a container holder section that retains and locates a container in alignment with the applicator punch. The means for retaining the punch holder is adapted to retain the punch holder that holds a plurality of punches on a frusto-conical surface, which is rotatable about a second axis, off-set from the first axis. It is located so as to position the frusto-conical surface so as to intersect the first axis and so that rotation of the means for retaining the punch holder individually locates each punch held by the punch holder into alignment with the applicator punch, between the applicator punch and the container holder section. Operation of the applicator punch causes the aligned punch to move towards the container holder section to excise a tissue sample.

Description

Received at IPONZ 2/12/2011 Patent No. 5 - Complete Specification TISSUE SAMPLIE DEVICE BASIC APPLICATION DETAILS Application No. Country 575341 New Zealand 578219 New Zealand Country Code Date of application NZ 5 March 2009 NZ 7 July 2009 We, Livestock Improvement Corporation, hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement.

Page 1 4908635 Received at IPONZ 2/12/2011 2 Tissue sampling device Field of the invention The present invention relates to apparatus for obtaining and storing tissue samples. Particular embodiments of the invention relate to sampling devices and 5 containers for retaining tissue samples. Other embodiments relate to applicators for taking tissue samples. Still other embodiments relate to carriers for containers retaining tissue samples.

Background of the invention In animal rearing or farming, it is sometimes desirable or necessary to test the 10 DNA of the animals. In order to conduct DNA testing, tissue samples need to be obtained from the animals.

It is often necessary to sample a number of animals at a time. The accuracy of the result of the DNA test done on the sample of one animal may be affected if the sample is contaminated with another animal's DNA.

Also, it is desirable that once a sample is obtained, it is placed into a container that is sealed, so that the sample can be safely transported to a laboratory where the sample can be analysed. To facilitate more rapid processing of tissue samples, a convenient carrier for groups of tissue samples may be needed.

It is further desirable that the animal from which a tissue sample is being taken 20 suffers a minimum amount of trauma. At the same time, the tissue sample needs to be of a sufficient size and quality so that the DNA material in the sample can be analysed.

Tissue samples may also be required for purposes other than the testing of an animal's DNA. 4908635 Received at IPONZ 2/12/2011 3 It is an object of certain embodiments of the invention to provide a device for obtaining tissue samples. A further or alternative object is to provide a device for storing tissue samples. A further or alternative object is to provide a device for transporting containers of tissue samples. An alternative object is to provide 5 devices for use in relation to tissue sampling that provide a useful choice.

Summary of the invention In one aspect, the invention broadly resides in an applicator for sampling tissue, the applicator including: a punch drive section including an applicator punch, which operates along a 10 first axis, and means for retaining a punch holder, and a container holder section that retains and locates a container in alignment with the applicator punch, wherein the means for retaining a punch holder is: adapted to retain a punch holder that holds a plurality of punches on a 15 frusto-conical surface; rotatable about a second axis, off-set from the first axis; and located: so as to position the frusto-conical surface so as to intersect the first axis; and so that rotation of the means for retaining a punch holder individually locates each punch held by the punch holder into alignment with the applicator punch, between the applicator punch and the container holder section, so that operation of the applicator punch causes aligned punch to move towards the container holder section to excise a tissue sample.

Further aspects of the present invention and further embodiments of the foregoing aspects will become apparent from the following description, given by way of example. 4908635 Received at IPONZ 2/12/2011 4 Brief description of the drawings Embodiments of the invention will be described, by way of example, with reference to the following drawing figures in which Figure 1 is a perspective view of one embodiment of a sampling device; Figure 2 is a partial view of the sampling device depicted in Figure 1 where the cutting punch has excised a tissue sample; Figure 3 is a partial view of the sampling device depicted in Figure 1, showing the tissue sample being dispensed into the sample holder; Figure 4 is a partial view of the sampling device depicted in Figure 1, where 10 the sample has been dispensed into the sample holder, the plug sealing the sampling device and punch being discarded; Figure 5(a) depicts the cross-section of an actuator, and the partial cross-section of a sampling device configured to cooperate with the actuator; Figure 5(b) depicts the sampling device and actuator shown in Figure 5(a), 15 where the plug is shown as being driven through the sample punch; and Figure 6 depicts a cross-section of a two-stage actuator and a partial cross-section of the sampling device.

Figure 7 shows an embodiment of an applicator device for use with the sampling device shown in Figure 1.

Figure 8 shows an exploded view of the applicator device shown in Figure 7.

Figure 9 shows a punch housing of the applicator device shown in Figure 7.

Figure 10 shows an exploded view of the punch housing shown in Figure 9. 4908635 Received at IPONZ 2/12/2011 Figure 11 shows a plan view of a punch holder as it may be fabricated.

Figure 12 shows a plan view of the punch holder shown in Figure 11 in its assembled form.

Figure 13 shows a cross-section through line DD in Figure 12.

Figure 14 shows a punch drive section of the applicator device shown in Figure 7.

Figure 15 shows a cross section through line EE in Figure 14.

Figure 16 shows a side view of the punch drive section shown in Figure 14.

Figures 17 to 20 show cross sectional views through the applicator device 10 shown in Figure 7, in four configurations.

Figure 21 shows a plan view of a transport container for containers of the sampling device shown in Figure 1, the transport container being in its open configuration.

Figure 22 shows a side view of the transport container shown in Figure 21, in 15 its closed configuration.

Figure 23 shows a plan view of the transport container shown in Figure 21, in its closed configuration.

Detailed description of the embodiments Throughout this specification, the invention will be described with reference to 20 applications for taking a tissue sample from an animal's ear. However this is not intended to be limiting and it should be understood that embodiments of the invention may be useful in other applications. 4908635 Received at IPONZ 2/12/2011 6 According to the embodiment shown in Figure 1, a sampling device 10 includes a sample punch 11 having an annular cutting edge 12, for punching through an animal's tissue to harvest a tissue sample. The annular cutting edge 12 is located on the leading face of the sample punch 11 and surrounds a bore 13 that extends 5 through the sample punch 11. The sampling device 10 also includes a plug 14 that is located in the bore 13, and that can move within the bore 13.

The sampling device 10 further includes a sample holder 15, including a container body 21 (see Figure 2) and an anvil 22. The anvil surrounds an opening 16 of a through-passage 24, through which a tissue sample removed by the sample punch 10 11 can pass to be deposited into the sample holder 15. The opening 16 is smaller in diameter than the annular cutting edge 12 of the sample punch 11. Further, the opening 16 is dimensioned so that it can be sealed by the plug 14.

The anvil 22 cooperates with the sample punch 11 to remove a tissue sample (see herein below). The anvil 22 includes a surface 17 constructed to withstand impact 15 with the sample punch 11, so that a tissue sample can be excised when this impact occurs. This operation may help maintain a substantially constant size of the tissue sample using the sampling device 10. The sample sizes will typically depend on the area defined by the annular cutting edge 12. Therefore, a larger punch can be used if a larger sample is required, whereas a smaller punch can be 20 used if only a small sample is required. In applications where a certain minimum sized tissue sample is required, by using a device that excises a substantially constant sized sample, then the sample size may be kept closer to the minimum.

The anvil 22 may, as shown, be a separate component to the container body 21 and engaged with the top of the container body. Alternatively, the anvil may be 25 integral with the container body. For instance, the anvil may be the end of the container body, which faces the sample punch 11 (i.e. the top end) and thus provides a surface against which the sample punch 11 can be driven. In embodiments with integral anvils, the container body 21 may have an opening located at the opposite end (to the anvil) through which the sample can be 30 accessed. 4908635 Received at IPONZ 2/12/2011 7 The operation of the sampling device 10 is now described with reference to Figures 2 to 4. The sample holder 15 and the sample punch 11 are each retained by a retaining device, such as a jaw of an applicator. The sample holder 15 and the sample punch 11 are held spaced apart from each other so that the opening 5 16 of the sample holder 15 aligns with the plug 14, which is in engagement with the sample punch 11. The ear of an animal is placed on the anvil 22 and the sample punch 11 driven towards the anvil 22. When the cutting edge 12 of the sample punch 11 impinges on the surface 17 of the anvil 22, a sample 30 from the tissue is harvested.

The sample 30 is located within the sample punch 11 and typically would not fall through the opening 16 of the sample holder 15, because its area is larger than the cross-section of the opening 16 (see in particular Figure 2). The sample 30 is therefore now positioned between the plug 14 and the opening 16. To place the sample inside the cavity of the container body 15, the plug 14 is driven toward and into the opening 16, thereby pushing the sample 30 into and through the opening 16 (see in particular Figure 3) into the container body 21. The used sample punch 11 will now either fall away, or can be removed from the plug 14, and can be expended (see Figure 4). In alternative embodiments described herein below, the sample punch 11 is retained in a flexible substrate.

The relative movement of the cutting surface 17 and the sample punch 11 toward each other causes the tissue to be penetrated. Accordingly, in alternative embodiments, the surface 17 of the anvil 22 may provide a cutting edge and the punch may have a surface against which the cutting edge impacts to excise tissue. This arrangement may however be less preferable, as instead of the smooth 25 surface 17, the top of the sample holder 15 will now have a cutting edge on it.

It will also be appreciated that the sample punch 11 may not have an edge that strictly cuts, but which instead tears the tissue, although it is expected that cutting edges may be preferred for most applications. 4908635 Received at IPONZ 2/12/2011 In Figure 1, the sample punch 11 is depicted to have a frusto-conical shape, and the plug 14 is depicted to have a generally tubular shape. However it will be appreciated that other shapes may be used.

Figure 2 shows an enlarged view of the upper end of the sample device 10 shown 5 in Figure 1. As previously described, the sample holder 15 includes the container body 21 for holding the sample, and the separate anvil 22. The through-passage 24 is in communication with the interior of the container body 21. The anvil 22 may be removably retained by the container body 21, for example, by friction. Alternatively it may be glued, bonded, or otherwise attached to the container body 10 21, in which case the container body 21 may have another opening through which the sample can be retrieved.

The anvil 22 includes an external portion 27 that is located outside the container body 21. A shoulder 28 abuts the wall 29 of the container body 21, acting as a stop to prevent the anvil 22 from further entering the container body 21. In an 15 alternative embodiment, the anvil may abut a seat that inwardly extends from the wall of the container body 21. The anvil 22 is thus prevented from moving past the seat and entering further into the container body 21. In this alternative embodiment, the anvil may optionally not include a portion that extends out of the opening of the container and the surface against which the punch operates to 20 remove a tissue sample may, for example, be substantially flush with the opening of the container or alternatively may be recessed within the opening on the container.

The anvil 22 and the plug 14 are configured to engage each other. For example, as shown in Figures 2 to 4, the through-passage 24 has a first section 25, which is 25 located adjacent to the opening 16, and a second section 26, which is located adjacent to the first section 25. The cross-section through the second section 26 is larger than that through the first section 25. The plug 14 may be resilient, for example due to being constructed from a suitable plastic or metal and have a chamfered protruding ridge 31 with an outermost diameter larger than the 30 diameter of the first section 25. In use, the chamfered ridge 31 is forced through 4908635 Received at IPONZ 2/12/2011 9 the first section 25. Once the ridge 31 enters the second section 26, its return to the first section 25 is blocked by the interior wall 38 of the anvil 22. The anvil 22 and the plug 14 thereby engage each other.

The plug 14 may further include a skirt 32 that is located at or toward the end of 5 the plug 14 that faces away from the sample holder 15. The cross-section of the plug 14 around the skirt 32 is larger than the cross-section of the opening 16. Therefore, the plug 14 is prevented from completely entering the through-passage 24, by the interference between the skirt 32 and the cutting surface 17. In alternative embodiments, the skirt 32 may be extended further than that shown in 10 the accompanying Figures. The extension may then be used to facilitate removal of the plug 14 (and the anvil 22 if the engagement between the plug 14 and anvil 22 is stronger than the engagement between the anvil 22 and the sample holder 15) at a laboratory. For example, the skirt 32 may be extended to form a T shape, which can be grasped by a manually or automatically operated mechanical device 15 for removal. The plug 14 may have a tapered head 33, which may assist to guide the plug 14 through the opening 16 in the event that the sample punch 11 and anvil 22 are slightly misaligned.

Other methods of securing the plug 14 with respect to the anvil 22 may be used. For instance, the plug 14 may generally have a cross-section that is larger than 20 that of the through-passage 24, so as to create an interference or friction fit along engaging surfaces of the plug 14 and anvil 22, without an interlocking type of engagement by a ridge or similar. The plug 14 may seal the through-passage 24 and therefore seal the sample holder 15 when it engages with the through-passage 24.

In the embodiment depicted, the sample punch 11 includes a radial extension 34 that extends into the bore 13. The radial extension 34 defines a cross-section that is slightly smaller than the cross-section of the plug 14. The friction between the radial extension 34 and the plug 14 retains the sample punch 11 on the plug 14. However, the plug 14 should not be so tightly retained by the extension 34 that its 30 passage out of the bore 13 is prevented. 4908635 Received at IPONZ 2/12/2011 An external portion of the sample holder 15 may be configured to engage an applicator for operating the sampling device 10. For instance the sample holder 15 has external grooves 37 (see Figure 4) that cooperate with an appropriately configured jaw or holder (not shown).

To facilitate identification of the tissue samples, each sample holder 15 carries a unique barcode or electronic identification device (EID). The location of the barcode or EID may depend on the type of the scanner used to read the barcode or EID. For instance, so that the barcode or EID can be read by a flatbed scanner, the barcode or EID may be provided on the bottom 39 of the sample holder 15, the 10 surface 17, or on a top surface 40 of the plug 14, or on two or more of these surfaces. The sample holder 15 may further be wholly or partially made from a transparent material that allows the interior of the sample holder (and hence the sample) to be visible from the outside. For instance, only the bottom surface 39 of the sample holder 15 is transparent. In another embodiment, the side wall of the 15 sample holder 15 is transparent.

A pneumatic applicator may be used to operate the sampling device 10. The pneumatic applicator according to one embodiment includes a punch housing for receiving the sample punch 11 and the plug 14. The punch housing also forms part of an actuator which, as described in more detail below, drives the sample 20 punch 11 and the plug 14. The applicator may include a locator which holds and locates the sample holder 15. An alignment device located between the punch housing and the locator holds these two components apart and in alignment with each other.

The punch housing may be divided into two parts by the actuator. The part that is 25 adjacent to the vessel locator houses the sample punch 11 and the plug 14 as described. The other part is an actuation chamber. In this embodiment, the actuation chamber is configured to receive gas from a pressurised gas cylinder. The supply of gas from the gas cylinder to the actuation chamber is controlled by a valve. 4908635 Received at IPONZ 2/12/2011 11 In one embodiment, when the valve is opened, pressurised gas is released into the actuation chamber, causing the actuator to move within the punch housing, creating pressure which acts on the sample punch 11 and the plug 14, causing movement of the sample punch 11 and plug 14 toward the sample holder 15. The 5 actuation chamber may include an O-ring therein, which is dimensioned to receive and retain the plug 14. When pressurised air (or other gas) is released, the air pressure acts on the plug 14, driving it out from the O-ring, following which the air may also act on the punch 11. With sufficient pressure, the punch 11 and plug 14 may shoot out from the punch housing, thus becoming a projectile, which impacts 10 the tissue and the anvil 22 to remove a tissue sample. Using an applicator that fires the punch 11 out from it may have the advantage of not requiring any mechanical actuator to extend through the ear, which may reduce the chance of injury to an animal if the animal bolts during removal of the sample. If an animal bolts while a mechanical actuator is through the ear, then there may be a risk of 15 the actuator tearing the animal's ear. In an alternative embodiment, pressurised air may act directly on the sample punch 11 and the plug 14, rather than via an actuator as described above.

The plug 14 and the sample punch 11 are sufficiently engaged so that the plug 14 is not pushed through the sample punch 11 until the sample punch 11 impacts on 20 the anvil 22. However, the plug 14 and the sample punch 11 should not be so tightly engaged that the plug 14 does not pass through the bore 13 by its own momentum after the sample punch 11 is stopped by the anvil 22.

Various alternative applicators may be used, including manual applicators similar to those currently used to apply ear tags. In some embodiments, the applicator 25 may be spring-loaded. The spring is normally held in a compressed state. When released, the spring forces the punch toward the anvil 22. The actuator in turn drives the plug 14 and the sample punch 11. When such spring loaded applicators are used, the sample punch 11 and plug 14 may form a projectile, similar to that described above. 4908635 Received at IPONZ 2/12/2011 12 In still further alternative embodiments, the sample punch 11 and plug 14 may be mechanically driven through its range of movement, for example by actuators described below with reference to Figures 5a and 5b or Figure 6. The actuators may be driven by compressed air, springs or by other drive mechanisms.

Figure 5a depicts one possible configuration of an actuator 51, and the plug 52 (which is similar to and performs the same general function as the plug 14). The plug 52 has an opening which leads into a recess 53. The actuator 51 includes a rod 54 that is dimensioned so as to fit into the recess 53. On its top end (i.e. the end that is away from the sample punch 11) the actuator 51 includes a head 10 portion 55. The head portion 55 is larger in cross section than the recess 53 of the plug 52 and also the bore 13 of the sample punch 11. In an alternative embodiment, the plug may not have a recess to receive the rod 54, which may instead act against the upper surface of the plug.

During an operation of the applicator, the plug 52 and the actuator 51 are 15 positioned so that the recess 53 aligns with the rod 54. The actuator 51 is driven so that the rod 54 mates with the recess 53. Alternatively the plug 52 may be positioned so that the rod 54 is already located in the recess 53 before the actuator 51 is driven. The rod 54 pushes the plug 52 and the sample punch 11, toward the anvil 22. Once the sample punch 11 is stopped by the anvil, continued 20 movement of the actuator 51 pushes the plug 52 through the bore 13 of the sample punch 11, and into the through passage 24 of the anvil 22 (not shown in Figure 5b).

Continued movement of the actuator 51 drives the plug 52 through the bore 13 until it partially or completely exits the bore 13 (see Figure 5b). The actuator 51 25 then retracts out of the recess 53 of the plug 52 and out of the bore 13 of the sample punch 11. The sample punch 11 is now free, or can be removed and can be expended.

As depicted in Figure 5b, the rod 54 may be driven until an underside 56 of the head portion 55 abuts a top surface 57 of the sample punch 11. This top surface 4908635 Received at IPONZ 2/12/2011 13 57 stops the movement of the rod 54 toward the sample holder. Here the plug 52 is shown to be pushed completely out of the bore 13. However, this is not essential and the result may be like that shown in Figure 3, where a portion of the plug remains within the bore of the punch.

Figure 6 depicts a further alternative applicator which includes a two-stage driving process (or two actuators), one for driving the sample punch 11 and one for driving the plug 52. The first driver (or actuator 61) pushes the punch 11 toward the anvil and causes the punch 11 to excise a sample from the animal's ear. The punch 11 carries the plug 52 with it. The second driver (or actuator 62) then causes the plug 10 52 to pass through the punch 11 to push the sample into the sample holder and engage with the anvil 22. It will be appreciated that the engagement between the plug 52 and the punch 11 may be such as to require less force to overcome than where a single stage applicator is used, as force to excise a tissue sample can be applied directly to the punch 11.

In some embodiments, the applicator may be configured to operate sampling devices that are arranged in an array. For instance, the vessel locator may include guide rails between which an array of sample holders can slide. To harvest a tissue sample, a sample holder is moved into alignment with the sample punch. The sample punch and the plug are then actuated to respectively harvest a 20 sample and deposit the sample into the sample holder. The sample punch is expended, and the plug is inserted into the sample holder to seal the holder. The sealed sample holder can then be moved along the guide rail and away from the punch housing. A new sample punch and plug assembly can now be placed into the punch housing, and the next sample holder in the array is now moved into 25 alignment with the new sample punch.

Figure 7 shows an embodiment of an applicator device of the type shown in Figure 6, having a two stage driving process. The applicator device 100 includes a punch drive section 101, a container holder section 102 and a handle section 103. These are operatively joined by a hinge section 104. As described in more detail below, 30 the punch drive section 101 operates under the control of the handle section 103, 4908635 Received at IPONZ 2/12/2011 14 to drive the sample punch 11 against the anvil 22 and also to drive the plug 14. The container holder section 102 retains the sample holder 15 in position while the punch drive section 101 operates.

Figure 8 shows an exploded view of the applicator device 100. The applicator 5 device 100 includes: an upper handle 105, a punch arm 106, a trigger 107, a lower handle 108, a trigger spring 109, a main spring 110, first and second cap axles 111, 112, a roll pin 113, a punch housing 114, a retainer 115, a sample container holder 116, an applicator punch 117, and a punch spring 118. The primary functional characteristics of the applicator device 100 are described below.

Figure 9 shows an enlarged view of the punch housing 114, together with a punch holder 120. Figure 10 shows an exploded view of the punch housing 114. The punch holder 120 carries, in this embodiment, eight sample punches 11. The punch housing 114 includes a punch body 121 through which extends a shaft 122 for the applicator punch 117. The punch holder 120 is retained in place by a clip 123, which engages with the punch holder 120. The clip 123 is secured to a dial 124 by an e-ring 125, with a punch body cover 126 providing a surface against which the dial 124 acts. The punch body cover 126 is engaged with the punch body 121 by a roll pin 127, creating a hinge. The punch body cover 126 also includes a cut-out section 126A over the portion of the punch holder 120 that holds the punch 11 to be used to excise a tissue sample.

The punch section 101 accordingly operates to hold the punch holder 120 so that a sample punch 11 is aligned with the applicator punch 117. The punch body 121 also provides a support for the flexible substrate 120A (see Figure 11) of the punch holder 120, preventing it moving upwards into the punch body 121 when the 25 punch section 101 is driven onto the container holder section 102. In this embodiment, the punches 11 remain attached to the punch holder 120 after they have been used to excise a tissue sample, instead of being discarded as described above for some alternative embodiments. This may have the advantage of avoiding sample punches 11 being discarded onto the ground. 4908635 Received at IPONZ 2/12/2011 After the sample punch 11 has been used to excise a tissue sample, the dial 124 is turned so as to align the next sample punch 11 with the applicator punch 117 (see Figure 8). Therefore, as described above, a clean sample punch 11 is used for each tissue sample, helping to avoid cross-contamination. When all punches 5 11 have been used, the punch cover 126 is opened, the punch holder 120 with the used punches 11 removed and replaced with another punch holder 120 containing another set of sample punches 11. The punching operation of the punch section 101 is described below.

Figure 11 shows a punch holder 120 as it may be fabricated. The punch holder 10 120 includes a flexible substrate 120A with, in the embodiment shown, eight apertures each holding a sample punch 11. To form the frusto-conical shaped sample holder 120, the ends 120B and 120C of the flexible substrate 120A are joined, for example by welding. Figure 12 shows an enlarged view of the punch holder 120 when the ends 120B and 120C are joined.

Figure 13 shows a cross-section through line DD of Figure 12. As previously described, the sample punches 11 each hold a plug 14. The angles, radiuses and other dimensions shown in Figures 11 to 13 are provided by way of example only.

Figure 14 shows a front view of the punch body 121, punch body cover 126 and dial 124. Figure 15 shows a cross section through line E-E in Figure 14, with part 20 of the punch holder 120 cut away. The punch holder 120 is retained by the punch body 121 and punch body cover 126. Figure 15 shows the shaft 122, through which the applicator punch 117 (see Figure 8) operates and in which the punch spring 118 (see Figure 8) is located. The shaft 122 includes a shoulder 122A (see Figure 15) and a neck 122B (see Figure 15). The shoulder 122A provides a 25 surface, against which the punch spring 118 acts. The neck 122B provides a guide and support for the applicator punch 117.

The punch body 121 engages with the punch arm 106 so as to be movable up and down with respect to the punch arm 106 in a reciprocating sliding motion. This sliding engagement is achieved by a tongue and groove arrangement. In 4908635 Received at IPONZ 2/12/2011 16 particular, a pair of opposing tongues 128 (one only visible in Figure 15) are provided on the punch body 121 and a pair of corresponding grooves 106A (see Figure 8) are provided on the punch arm 106. The interior side of the punch body 121 includes a shoulder 129 that presses against the retainer 115, thereby 5 preventing the punch body 121 being forced off the grooves 106A by the punch spring 118.

Figure 16 shows a side view of the punch body 121 and the punch cover 126. The punch cover 126 is opened about a hinge H, as shown by arrow A. The punch cover 126 includes two buttons 130, one on each side (only one visible in Figure 10 16), which provide a releasable interlocking engagement between the punch cover 126 and the punch body 121. The buttons 130 are gripped and pulled to release the interlock and allow the punch cover 126 to be opened to allow replacement of the punch holder 120 as required.

Figure 17 shows a cross-section through the applicator 100 when it is in its fully open position, with a sample holder 15 retained in the sample container holder 116. The upper handle 105 and lower handle 108 of the applicator 100 are biased into this position through the action of the main spring 110 on the hinge portion 104. In this position the punch spring 118 is also at its full extension, stopped by the punch body 121 abutting the retainer 115. The punch body 121 therefore extends so as to entirely cover, or alternatively substantially cover, the applicator punch 117. Also, the trigger 107 in the hinge portion 104 is pressed outwards by the trigger spring 109.

The sample container holder 116 is pivotally mounted to the upper handle 105 (which forms the lower part of the jaws of the applicator 100) via a pivot 116A (see 25 Figure 8). The sample container holder 116 holds the container in place by an edge recess 116B (see Figure 8) extending into the grooves 37 (see Figure 4) of the sample container 15. The edge recess 116B may be dimensioned to frictionally engage with the grooves 37. 4908635 Received at IPONZ 2/12/2011 17 Figure 18 shows the applicator 100 when the upper and lower handles 105, 108 are pushed together to a point where the punch drive section 101 first contacts the container holder section 102. The punch spring 118 is still at full extension. At this point the punch 11 impacts the anvil 22. The force of impact is limited by the 5 spring constant of the punch spring 118, because as soon as the force exceeds that required to compress the punch spring 118 (inclusive of an additional force to accommodate friction), the punch body 121 starts to slide up the punch arm 106. Accordingly, the punch spring 118 should have a sufficiently high spring constant to allow the punch 11 to excise a tissue sample from an animal's ear, but not so 10 high so that the applicator can not readily be closed by hand from the position shown in Figure 18 to the position shown in Figure 19.

When the applicator 100 is in the position shown in Figure 18, the trigger 107 has been pressed in, by a guide pin 131 of the upper arm 105, from its position shown in Figure 17, but still prevents the main spring 110 from forcing the punch arm 106 15 back to its open position because its movement is blocked by a projection 132 in the hinge portion 104. When the applicator 100 is in the position of Figure 18, the applicator punch 117 is perpendicular to the upper surface 105A of the upper handle 105, on which the sample container holder 116 is supported. The applicator punch 117 is therefore aligned with the opening through the anvil 22.

Figure 19 shows the applicator 100 when the upper and lower handles 105, 108 are fully closed. The punch body 121 has been forced upwards against the action of the punch spring 118. However, the applicator punch 117, being secured to the punch arm 106 continues to move with the punch arm 106 and therefore is effectively extended out from the punch body 121, through the punch 11. The 25 applicator punch 117 therefore is moved into the through passage 24 of the anvil 22. In this way, the applicator punch 117 pushes the plug 14 out from the punch 11 and into the anvil 22. As explained previously, this both pushes the excised tissue sample into the sample holder 15 and seals the sample holder 15.

As the applicator 100 closes past the position shown in Figure 18, the punch body 30 121 continues to rotate. The resulting turning moment on the sample container 4908635 Received at IPONZ 2/12/2011 18 holder 116 causes it to rotate about the pivot 116A (see Figure 8). This results in the through-passage 24 remaining aligned with the applicator punch 117, as shown in Figure 19.

At the point of maximum closure, the trigger 107 is pushed sufficiently in by the 5 guide pin 131 to clear the projection 132. This releases the main spring 110, which moves the punch arm 106 to its open position, despite the arms 105, 108 still being closed. This configuration is shown in Figure 20. The dial 124 can then be turned to align the next punch 11 with the applicator punch 117 and the handles 105, 108 opened to allow the trigger spring 109 (see Figure 17) to push the trigger 10 107 back out past the projection 132. The container 15, containing the tissue sample and closed by the plug is removed and another container placed in the sample container holder 116, ready for taking the next tissue sample. The sample container holder 116 may be biased to return its position shown in Figure 18.

Figure 21 shows a transport container for the containers 15 in an open 15 configuration. The transport container 200 may be constructed from a sheet 201, which may be plastic sheet or a cardboard sheet. The sheet 201 may be a single sheet or a multi-ply sheet. Three fold lines 202 - 204 extending across the transport sheet 201 to allow it to be folded into its closed configuration. The sheet 201 includes a head section 205, which is received by a slot 206 to retain the 20 sheet 201 in its closed configuration. A side and top view of the transport container 200 in its closed configuration is shown in Figures 22 and 23 respectively.

The transport container 200 includes a foam block 207 adhered to the lower surface of the sheet 201 in the area between the fold lines 203 and 204. The foam block 207 has eight apertures through it, so that when the transport container is in 25 its closed configuration there are eight holes that extend through the two layers of the sheet 201 and the foam block 207. The holes are dimensioned so as to receive and retain eight of the containers 15, with an interference fit.

The upper flat surface 208 of the transport container 200 may be used to record and uniquely identify each of the eight containers 15 using a combination of 4908635 Received at IPONZ 2/12/2011 19 sample position, animal identification and a unique bar-code on the bottom of the containers 15. Once the tissue sample is taken, the first sealed container 15 is placed into the first position of the transport container 200 and the animal's identification number is recorded on the surface 208 immediately to the right 5 (referring to the orientation of the transport container 200 shown in Figures 22 and 23) of that container 15. The second tube containing the second sample is place into the second position and the sequence followed until all storage positions are filled.

A plurality of the transport containers 200 may be placed vertically into a box or an environmentally controlled container in an alternating fashion, to maximise storage space. The transport containers 200 are then shipped to a laboratory for testing. On arrival at the laboratory, the transport container 200 is unfolded to its open configuration so that the surface 208, with the animals' identification is now facing the surface of the table, in the same plane as the bar-code on the bottom of each of the containers 15 (the foam block 207 is retained in its original orientation).

The underside of the unfolded sheet 201 and the bottoms of the containers 15 can then be scanned on a flat-bed scanner (or similar device) and the bar coded container's identification may be matched to the animal's identification by way of character recognition of the animal's identification, for example using OCR 20 software or by a person reading the markings on the sheet 201. Where alternative identifiers are used on the containers 15, for example EID identification, then the unfolded configuration may also facilitate reading of the identifier. The foam block 205 is then separated from the sheet 201 and the individual containers 15 positioned above the appropriate hole in a row of eight holes of a 96-well sample 25 tube holder (not shown), configured as 8 x 12 rows of holes. The individual (or all eight) containers 15 are then forced through the bottom of the foam block 205 into their new position in the 96-well sample tube holder. The 96-well holder is progressively filled with strips of 8 samples per row.

Received at IPONZ 2/12/2011 The sheet 201 and foam block 207 can be discarded or recycled, depending on the material used for construction. The dimensions of the transport containers 200 are given by way of example only.

It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention. 4908635 Received at IPONZ 2/12/2011 21

Claims (1)

1. Claims: 1. An applicator for sampling tissue, the applicator including: a punch drive section including an applicator punch, which operates along a first axis, and means for retaining a punch holder, and 5 a container holder section that retains and locates a container in alignment with the applicator punch, wherein the means for retaining a punch holder is: adapted to retain a punch holder that holds a plurality of punches on a frusto-conical surface; 10 rotatable about a second axis, off-set from the first axis; and located: so as to position the frusto-conical surface so as to intersect the first axis; and so that rotation of the means for retaining a punch holder individually 15 locates each punch held by the punch holder into alignment with the applicator punch, between the applicator punch and the container holder section, so that operation of the applicator punch causes aligned punch to move towards the container holder section to excise a tissue sample. 4. An applicator for sampling tissue as claimed in claim 1 and substantially as 20 hereinbefore described with reference to Figures 7 to 20 the accompanying drawings.