WO2024170445A1

WO2024170445A1 - Improvements to biopsy devices

Info

Publication number: WO2024170445A1
Application number: PCT/EP2024/053373
Authority: WO
Inventors: Richard Gerardus Johannes DOHMEN; Jonathan Jan Breemhaar; Miguel Augusto da Silva MOURA; Nick VAN ZOMEREN
Original assignee: Mosa Meat BV
Current assignee: Mosa Meat BV
Priority date: 2023-02-14
Filing date: 2024-02-09
Publication date: 2024-08-22
Anticipated expiration: 2025-08-14
Also published as: NL2034141B1

Abstract

The invention relates to improvements to biopsy devices. The current device allows for obtaining a biopsy sample directly into a cell culture medium or other liquid containing vessel, without an external transfer step.

Description

DESCRIPTION

TITLE: IMPROVEMENTS TO BIOPSY DEVICES

TECHNICAL FIELD

The invention is in the field of biopsy devices, specifically in the field of biopsy devices for obtaining live animal cell samples. The improvements to traditional biopsy devices disclosed herein allow for a sample obtained by biopsy to be immersed in a cell culture medium without the need of an intermediate step of biopsy material transfer from the biopsy device to an external medium containing vessel.

BACKGROUND OF THE INVENTION

Biopsy devices, also known in certain configurations as biopsy guns, are well known in the art as a straightforward way to obtain biological samples. Biopsy guns in particular improve biopsy conditions by allowing for better automated handling of biopsy needles (which may always be used without a biopsy gun in more traditional devices). Most biopsy devices work by having a protruding needle that is inserted into the area of tissue of the animal where a sample is to be collected from, this needle being adapted to retrieve a sample by having a sampling cavity and a sheath, basically a second needle of larger diameter than the needle, concentric with the needle and surrounding it, that can retract to expose the sampling cavity and, by a mechanical action on the biopsy device (for example pushing a trigger on a biopsy gun) usually by means of a pre-loaded spring or similar mechanism, can advance over the needle towards the needle tip and over the sampling cavity, cutting the tissue by means of a sharpened distal edge and at the same time sealing the sampling cavity. The needle, covered by the sheath, is then removed from the tissue being sampled and the sample is collected by retracting the sheath and exposing the sample in the sampling cavity, usually either by removing the needle from the gun for posterior collection of the sample, or expelling the sample from the needle whilst still attached to the gun, making use of a mechanism on the gun adapted to do so. A good example of this state of the art can be found in Fig. 4 of WO 2011/034046 Al . The type of sampling cavity in this prior art document is called a “side notch”. Other types of biopsy devices exist in the prior art, using different solutions from the needle/sheath combination. Another common type of biopsy device are ones that present with a simple hollow needle, collecting a “full core” sample. When there is a need to prevent the cells in a sample from dying, culture medium must be provided to the same. This is done by transferring the sample from the collection cavity or whatever equivalent means the specific biopsy device uses, and posterior immersion in culture medium present in an external vessel, implying a biopsy sample material transfer step involving risk of contamination. Also, it may not be critical to maintain the cells in the sample alive, but to simply transfer them to a liquid medium other than cell culture medium to fulfil any sort of processing need. As long as this needs to be done in a sterile fashion, the state of the art does not provide an adequate solution. Also, the state of the art does not provide a solution to carrying out the sterile transfer operation within the biopsy device itself, without recourse to an external vessel.

There is thus a need to ameliorate these problems, as disclosed in the present invention.

US2022/312227A1 discloses a needle biopsy device that does not allow a chamber to be filled with fluid, by disclosing no discernible means to maintain watertightness of a collection vessel and not disclosing the presence of a fluid anywhere in the specification. The main problem solved by this publication is to provide a wiper that moves a biopsy sample from the needle to a chamber. This is completely distinct from the present invention.

US7637872B1 discloses an aspiration assisted biopsy device with a collection vessel. This device is adapted to biopsies of very specific body parts where a fluid is present, in this case bone marrow. The vessel is not traversed by a biopsy needle but is instead made in such a way that a biopsy needle connects to one half only, and the other half connects to an aspiration system. There is no way to transmit a mechanical movement to a biopsy needle structure through the vessel as in the present invention. As such, a needle comprising two different structures, such as a sheath and an internal needle is impossible to be put into operation. The features of the device do not allow for the presence of a liquid in the vessel prior to the biopsy step itself, since this liquid would be aspirated during operation of the device. This device does not and cannot by any adaptation solve the problems solved by the present invention.

WO95/25465 discloses a biopsy device with several sample deposit sites. There are mechanical means provided to guide the sample to these deposit sites. These sites are in no way adapted to hold a liquid and cannot in any way operate in a fashion to solve the problems solved by the present invention. US2020/0187922 discloses a biopsy device with a rotating set of deposit zones, containing a carrier medium that adheres to the tissue sample. The carrier medium is not a fluid/liquid. The sample that is adhered to the carrier medium may be deposited in an empty collection vessel. There is no way in which the watertightness of this system can be maintained and as such the presence of a liquid to immerse the sample in is impossible in any part of the system. The disclosure in this document does in no way solve the problems identified in the current invention.

US2006/0224082A1 discloses a biopsy device with a sample collection chamber and the ability to place a marker in the biopsied tissue, this marker being a flowable substance. The collection chamber does not hold a liquid nor is it configured in any way to be able to hold one.

SUMMARY OF THE INVENTION

The inventors describe a new biopsy device with an inline collection vessel.

The preferred embodiments of the invention are as follows:

In a preferred embodiment, a biopsy device comprising an inline collection vessel (10) and a collection needle.

In another preferred embodiment, a biopsy device wherein the collection vessel is mounted on the collection needle, the collection needle traversing the collection vessel in a straight line.

In another preferred embodiment, a biopsy device wherein the collection vessel comprises an internal cavity adapted to receive a biological sample and/or a liquid.

In another preferred embodiment, a biopsy device wherein the collection vessel comprises two perforable seals (11), the perforable seals optionally containing two pre-made orifices.

In another preferred embodiment, a biopsy device wherein the collection needle comprises an internal needle (12) with a collection cavity (13) and a monolithic (20) or notched (21) sheath, concentric to and on the outside of the internal needle (12).

In another preferred embodiment, a biopsy device wherein the notched (21) sheath comprises a notch (22) of a size not smaller than required to expose the collection cavity (13) when this is aligned with the notch and wherein the notched sheath may optionally display alignment markings to determine the position of the collection vessel (10) in relation to the notch (22).

In another preferred embodiment, a biopsy device wherein the collection vessel is contained within the body of a biopsy gun, configured to be able to open and close to insert and remove the collection vessel.

In another preferred embodiment, a biopsy device wherein the collection needle is supported by mechanical supports built on the body of the gun, the mechanical supports built in line with the collection vessel seals (11) to allow guiding the collection needle through the seals.

In an alternative preferred embodiment, a process to operate a biopsy device with an inline collection vessel (10) comprising the steps of: a. Providing a sealed collection vessel (10) with two seals (11) containing a liquid, such as cell culture medium; b. Traversing the body of the collection vessel with a collection needle inserted through the seals; c. Inserting the distal end of the collection needle in an animal tissue to be biopsied; d. Exposing the collection cavity (13) to the animal tissue; e. Cutting the animal tissue by causing an opposing movement between the internal needle and the sheath. f. Retracting the internal needle until the collection cavity is contained inside the collection vessel; g. Releasing the sample inside the collection vessel; h. Fully removing the collection needle from the collection vessel allowing the self-sealing seals (11) to seal the collection vessel.

In another preferred embodiment, a process, wherein between steps f) and g) there is a step of retracting the monolithic (20) sheath and exposing the collection cavity to the inner medium of the collection vessel.

In another preferred embodiment, a process wherein between steps b) and c) the notch (22) of a notched sheath (21) is aligned until contained inside the collection vessel (10) and between steps f) and g) there is a step of aligning the collection cavity with the notched (21) sheath notch (22), exposing the collection cavity to the inner medium of the collection vessel.

In an alternative preferred embodiment, a biological sample inline collection vessel for a biopsy device, comprising two seals on opposite sides, able to be traversed by a biopsy collection needle.

In another preferred embodiment, a vessel wherein the seals comprise a screwed or forced in plug or membrane.

In another preferred embodiment, a vessel wherein the plug or membrane optionally comprises a premade orifice of a dimension that allows self-sealing.

In another preferred embodiment, a vessel wherein the vessel is opaque or transparent, wherein the vessel is preferably made of metal, glass or polymeric material.

In another preferred embodiment, a vessel wherein the vessel comprises securing means to the collection needle, such as mechanical anchors.

In another preferred embodiment a vessel wherein a skin seal is placed or formed either on an end of the vessel or placed or formed on one of the seals, the side of the vessel or the seal being the one closest to the distal end of the collection needle.

In another preferred embodiment a vessel wherein a holding chamber is formed at the distal end of the vessel or on the outside of the distal seal, by a holding chamber part comprising an orifice and a cover for the orifice.

In another preferred embodiment a vessel wherein a bellows is mounted in a connecting fashion between the collection vessel and the sheath, on one or both sides of the vessel, or between a collection vessel seal and the sheath, on one or both seals of the collection vessel.

DESCRIPTION OF THE DRAWINGS

Fig. 1 - Collection vessel.

Fig. 2a - Collection vessel and monolithic sheath combination ready to use.

Fig. 2b - Collection vessel and monolithic sheath combination after collection of a sample. Fig. 2c - Collection vessel and monolithic sheath combination after emptying of collection cavity.

Fig. 3a - Collection vessel and notched sheath combination ready to use

Fig. 3b - Collection vessel and notched sheath combination after collection and sample release into vessel.

Fig. 4 - Mid section cut view of a collection vessel with plugs and optional preformed orifice.

Fig. 5 - Example of a bellows, mounted on the proximal side of the sheath connecting it to the vessel.

Fig. 6 - Example of a skin seal formed on the vessel seal.

Fig. 7 - Example of a vessel with a holding chamber.

Reference signs:

10 - Collection vessel;

11 - Vessel seal, showing optional preformed orifice;

12 - Internal needle;

13 - Collection cavity on internal needle;

14 - Sample obtained by biopsy;

20 - Monolithic sheath;

21 - Notched sheath;

22 - Notch on notched sheath;

23 - Skin of the animal to be biopsied;

24 - Bellows; 61 - Skin seal;

61a - Skin seal on holding chamber part;

71 - Holding chamber;

72 - Holding chamber part;

73 - Holding chamber cover;

74 - Holding chamber orifice.

DETAILED DESCRIPTION OF THE INVENTION

The invention described herein aims primarily to solve the problem of transferring biological samples biopsied from the sampling area of an animal, using a biopsy device, into a liquid, preferably a culture medium solution, in a sterile fashion.

A culture medium is a solution used to maintain cells alive, preferably in cell culture conditions. Cell cultures consist of animal cells, isolated from their original living organism (the animal), subject to artificial conditions that replicate the biological processes that allow them to proliferate or differentiate. These artificial conditions may comprise placing the cells in an appropriate bioreactor, petri dish or any other industrial or laboratory equipment adequate for the culture of cells. The cells are mostly surrounded by, or immersed in, a cultivation medium appropriate for culturing the specific cell type. This medium can be specifically tailored to promote proliferation, differentiation, or both.

Several pre-formulated media for cell culture are available in the market. These can be “basal media”, usually based on salt solutions with several compounds added to allow for the culture of specific cells or “complex media”, that support a wide range of mammalian cells. Examples of well-known basal media are MEM (Minimum Essential Medium) or DMEM (Dulbecco’s Modified Eagle Medium), amongst many other types.

Culture medium can be used as a temporary solution to keep the cells healthy (i.e. alive) between the moment of biopsy and posterior transfer to an appropriate cell culture device, including any intermediate steps required, such as dissociation of individual cells from the collected tissue. An example of cells that can be cultured are cells obtained from a biopsy of an animal tissue, in vivo. For example, in the technical area of cellular agriculture, cells normally used for human consumption, such as primary cells like Fibro-Adipogenic Precursors (FAPs) or Satellite Cells (SCs), also known as myosatellite cells, are obtained by biopsy from animals usually consumed by humans, for example mammals such as bovines, ovines or porcines among others.

Specifically in the field of cellular agriculture, but also for the broader biotechnology field, sterility of the biopsied sample is of the utmost importance to prevent contamination of the cell samples. Contamination may lead to, for example, unsuccessful cell cultures or misleading analysis results.

By providing, with this invention, a solution to obtain biological samples immersed in a liquid with no transfer steps external to the biopsy device, the inventors solve at least three important problems: maintaining the samples in a liquid, be it medium or any other liquid necessary for any process downstream of the biopsy without contamination; maintain the cells within the biopsied tissue alive, when using cell culture medium or any other appropriate solution for this end and; allow the biopsy device to replace the step of transfer of a sample to an external vessel by its own novel internal functions, fully eliminating this step from the process.

Biopsy device with a collection vessel

The inventors propose providing a biopsy device with a collection vessel (10), filled with a liquid, preferably a cell culture medium. The collection vessel is mounted on the biopsy needle, the biopsy needle traversing the collection vessel. Due to this type of assembly, the collection vessel may be said to be inline with the collection needle of the biopsy device. The term inline will be used to signify this alignment in this specification. Whether the term is written down or not, and many times, for brevity, it won’t, whenever the “collection vessel” is referenced, it is to be assumed this is taken to mean an “inline collection vessel”.

Preferably, the inline collection vessel is shaped as a hollow cylinder, mounted in a concentric fashion on the collection needle. The collection needle may comprise an internal needle (12) and a sheath (20 or 21). Both the internal needle and the sheath can be movable. The collection may be done by a side notch type of biopsy or by obtaining a full core. The side notch option is preferred due to sterility concerns. The internal needle may present with a sampling cavity (side-notch) or be hollow (full core).

The collection vessel needs to be removable from the biopsy device to allow for transport of biopsy samples. This is accomplished by providing means to slide it over the collection needle and closing the two openings (11) previously occupied by the needle. This closure may be accomplished by providing self-sealing means, such as post-puncture, selfsealing membranes or plugs. In general, this description will refer to these structures as the vessel seals.

The inline collection vessels may be seen as consumables, provided filled with a liquid, such as cell culture medium, and presenting with two seals on opposite sides that can be perforated by the collection needle before the biopsy operation is performed. The needle should traverse the vessel from one seal to the other. Optionally the collection vessels and/or the collection needle may present with anchoring means to maintain their relative positions. One surface of the collection vessel may be openable (screwed on, for example) to allow for the later discharge of its contents - preferably this may be one of the two bases of a cylindrically shaped vessel. Optionally, this discharge can be done by removing the seals, if these are optionally removable.

In operation, the biopsy device is first loaded with a (preferably sterilized) collection needle. A collection vessel filled with the desired liquid is loaded on the collection needle. The collection vessel may be filled by pouring the liquid in before applying the second seal but after applying the first seal, or it can be filled after completely sealed from a luer connection or equivalent applied in any suitable part of the vessel or the seals. The vessel may also be filled by luer or equivalent connection only after being traversed by the collection needle, so that the needle first goes through an empty vessel. Filling by luer connection or equivalent increases the air pressure inside the vessel, so the excess atmosphere will escape either through the luer, or by pushing on a self-sealing pre-made orifice in a seal, or eventually from in-between the collection needle and the seal area. The distal end of the collection needle (the end further from the operator) is inserted into the animal from which a sample is to be taken. In the side notch version, the collection needle slides into the animal with the sheath covering the collection cavity present on the internal needle. At this stage, when perforation of the skin of the animal happens, the side notch version of the internal needle is preferred since the side notch allows for the tip of the needle to be solid and as such for the sheath to keep the collection cavity closed during insertion. This further prevents contamination of the sampling cavity with material not from the area to be biopsied.

A pre-incision on the animal’s skin may be performed to cause the needle tip to not have to perforate the skin and as such reducing contamination or helping reduce needle blunting, extending the lifetime of the material. The area around the incision or needle penetration point is preferably shaved of any hairs and disinfected. The vessel may be provided with a skin seal (61), which is ring-like, of a rectangular, square or O section or a lip like structure placed or formed either on the end of the vessel that is closer to the animal’s skin or placed or formed on the actual seal placed on the end of the vessel closer to the animal’s skin, that skin seal being appropriate to further seal the space between the animal’s skin and the vessel by creating an isolated space when the vessel is pushed against the skin. The shaved and sterilized area on the animal should by large enough to accommodate the skin seal.

The vessel may also be provided with a sterile holding chamber (71), where the needle tip may rest after insertion through the seals of the vessel and before use. The holding chamber function is explained in more detail in the embodiments section ahead.

After inserting the needle in the animal (23) and reaching the desired depth/position, the internal needle may be pushed forward from within the sheath, allowing biological material to fill the collection cavity. A relative opposing movement between the sheath and the internal needle is then caused. The sheath may be extended forward over the collection cavity, cutting the sample and enclosing it within the collection cavity. Optionally, the sheath may retract over the internal needle exposing the collection cavity to the biological material and later extend again over the collection cavity. These movements of the internal needle and/or the sheath may be performed by manual handling of the devices, for example by having handling means, such as, for example, plungers or handles, in the proximal (closest to the operator) end of the collection needle or automatically by the use of triggers, for example operated by a combination of trigger(s) and spring(s). These means are outside the scope of the invention but could be any such as traditionally used in biopsy guns known in the prior art. The provision of these means together with the collection needle as disclosed in this invention would transform the novel biopsy device into a novel biopsy gun. This is a preferred presentation for the invention, considering how biopsy guns facilitate the handling of biopsy devices. It is also possible to provide the collection vessel inside the biopsy gun itself. In this case, the biopsy gun would present with opening means to allow insertion or removal of the collection vessel. After the biological sample (14) is contained within the collection cavity, the collection needle may be pulled through the collection vessel in the distal-proximal direction, or the internal needle only may be retracted in the same direction. When the sample within the collection cavity reaches a position where it is completely inside the collection vessel, the sample is released from the collection cavity. This may happen by retracting the sheath over the internal needle, thus exposing the sample to the medium or by having an opening (22) on the sheath, located inside the collection vessel, that will expose the sample to the medium as the internal needles slides past it. In case the collection vessel is located inside a biopsy gun, the biopsy gun may have built in guiding elements to help support the collection needle and guarantee a linear movement inside the vessel, preventing lateral forces that could damage the seals from arising, as could eventually happen when manually supporting the vessel outside of a biopsy gun. It may be necessary to provide manual agitation to the biopsy device to dislodge the sample (i.e., shaking) and preferably the operation is done in such a way as to maintain the distal seal opening of the vessel against the skin of the animal (i.e. the outer surface of the area being sampled) during the retraction step. This will further help prevent any contamination of the collection needle as it is pulled through the vessel. The skin/outer surface is assumed to be disinfected as part of the preparation steps for a biopsy. The collection needle may optionally be coated in an antiseptic solution to avoid pulling/pushing biological contaminants into the vessel. The seal should completely surround the collection needle while it slides in it, pushing any contaminants from the outer surface of the collection needle as it slides along it, keeping the contaminants on the outer surface of the needle.

In every step where the sheath is moving (except in the final separation of the collection vessel from the collection needle for transport of the sample), it may be advantageous to have the collection vessel move concurrently with the sheath instead of allowing the sheath to move inside the vessel. This prevents the introduction of possible pathogens and provides for the maintenance of a better seal around the collection needle. Several different options are obviously possible.

The collection vessel, now containing a sample, can be transported and processed in a laboratory or any other appropriate facility by opening the openable surface, for example a screw-on base of a cylindrically shaped vessel, or by removing or re-perforating the seals provided on the openings. Exemplary Embodiments of the Invention

All the embodiments described below can, except where they would be clearly structurally impossible such as combining both the monolithic sheath and notched sheath embodiments, be combined with each other.

Collection vessel and monolithic sheath combination.

In this embodiment, exemplified in Fig. 2, the collection vessel (10), provided with cell culture medium or another liquid, is mounted on the collection needle by perforating it through the openings (11) and sliding it over the collection needle as previously described. The perforated surfaces of the collection vessel are thus in contact with the sheath (20). The internal needle

(12) comprises a side-notch as a collection cavity (13). The sheath is of monolithic construction, i.e., no special opening is created on its surface to allow access to the collection cavity on the internal needle. After these operations the biopsy device is considered primed to obtain a sample (Fig. 2a). After a biological sample (14) is collected in the collection cavity

(13), by any combination of movements of the internal needle or the sheath, the collecting needle, presenting with the sheath covering the collection cavity, is retracted through the collection vessel up to a point where the collection cavity (13) and thus the sample (14) is fully contained within the collection vessel (fig. 2b). At this point, the sheath is retracted (fig. 2c) exposing the collection cavity to the internal liquid environment of the collection vessel. Mechanical agitation (shaking of the biopsy device) may be required to dislodge the biological sample from the collection cavity. The collection needle is then removed fully from the collection vessel, preferably with the sheath having moved to a position covering the collection cavity, to prevent leaks.

Collection vessel and notched sheath combination.

In this embodiment, exemplified in Fig. 3, the collection vessel (10), provided with cell culture medium or another liquid, is mounted on the collection needle by perforating it through the openings (11) and sliding it over the collection needle as previously described. The perforated surfaces of the collection vessel are thus in contact with the sheath (20). The internal needle (12) comprises a side-notch as a collection cavity (13). The sheath (21) includes an opening (22), with dimensions appropriate to expose the collection cavity (13). When inserting the collection needle in the collection vessel, this opening is to be fully contained within the vessel (Fig. 3a). This can be done by visual inspection of the sheath through a transparent vessel or by using visual markings on the sheath (on a version where a biopsy gun is used, non-alignment should be impossible due to the body of the gun fixing the relative positions of all elements). After a biological sample is collected in the collection cavity, by any combination of movements of the internal needle or the sheath the collecting needle, presenting with the distal end of the sheath covering the collection cavity, is retracted through the collection vessel up to a point where the collection cavity (13) and thus the sample (14) are inside the collection vessel (10), concurrent with the sheath opening (22) (fig. 3b). Mechanical agitation (shaking of the biopsy device) may be required to dislodge the biological sample from the collection cavity. The collection needle is then removed fully from the collection vessel, preferably with the internal needle having moved to a position where both the sheath opening and the collection cavity are closed, to prevent leaks.

Manual vs biopsy gun version

Both previous embodiments may present as a biopsy gun. This would be an automated version when compared to a manual version of the biopsy device. By manual version it is meant that all the operation, including extending or retracting either the sheath or the internal needle, in any combination, is done by direct manual manipulation of these. By biopsy gun version, it is meant that some of these operations may be automated or semi-automated by mechanical means typically found in biopsy guns, such using manual triggers and springs to create per determined movements of certain parts.

In a biopsy gun version of the biopsy device, it is possible that the collection vessel is contained within the body of the biopsy gun, which may open to allow the insertion or removal of the collection vessel. Another advantage of a biopsy gun with internal collection vessel version of the invention is that the collection needle, both when being inserted or removed from the vessel, may be guided with the aid of mechanical supports built on the body of the gun. This will help prevent unforeseen movements away from linearity which could damage the vessel or it’s openings.

When using a notched sheath, the gun may allow for an easier positioning of the notch inside the vessel, by limiting position of the several elements due to its construction.

Bellows addendum A bellows-like structure (24) may be added in a connecting fashion between the collection vessel and the sheath, on one or both sides of the vessel. An example is shown in fig.5, with the bellows disposed between the vessel and the sheath. The bellows is a hollow structure, preferably made from an elastic material such as rubber, having an orifice traversed by the sheath that seals the sheath/bellows connection under pressure. The bellows can then be connected to the vessel in any way foreseen in the prior art, such as having a fitting slot on the seal or vessel, etc. Bellows may be present on one or both sides of the vessel and may serve a dual function of further sealing the connection between the vessel and sheath or providing for a movable seal that can accommodate the movements of the sheath in relation to the vessel. This can be seen in fig 5, where the bellows is shown more and less compressed, meaning that it has followed the relative motion between the sheath and the vessel.

The collection vessel

The inline collection vessel is, in its most basic form, a container for a liquid that presents with two perforable surfaces in a straight line when taken through the liquid containing cavity. Ideally, this vessel is of a mostly cylindrical shape, for ease of handling, maximizing the internal volume and possibility of mass manufacturing. As an example, the vessel may be a plastic, metal or glass cylinder (other suitable materials may be possible) with both ends open. A seal, for example a plug (best exemplified in fig. 4) or membrane (best exemplified in fig. 1), may be, on either side, pushed onto or screwed to the open cylinder by means of a screwable seal holder. The plug or membrane of the seal may be as thick as required to guarantee selfsealing properties as the collection needle slides in and out of it. The plug or membrane may be deformable to better accompany any movements of the collection needle and push contaminants along the outside of the needle, keeping them from entering the vessel.

The seal may preferably have a preformed through orifice, with a diameter that allows maintaining the self-sealing properties of the seal material, to help guide the initial insertion of the collection needle and diminish the force necessary to perforate it. The orifice also has the advantage of minimizing the probability of the internal needle or sheath shaving off any of the plug or membrane material during insertion. Shaving off is also prevented by presenting the solid conical tip protruding from the sheath during insertion.

The seal may be forced into the vessel akin to a cork being applied to a bottle, and it may be fully contained within the inner diameter of a cylindrical vessel after applied, or it may present with a part that is wider than the diameter of a cylindrical vessel and show on the outside of the vessel - this later will usually be the case when the seal is of the screwing type, but the forced in version may also present with the wider region to better seal or prevent excessive insertion into the vessel.

The membrane or plug may be made from natural or synthetic materials, preferably polymers, preferably elastomers, such as silicone or polyurethane rubber.

With manual loading of the vessel on the collection needle, the vessel is preferably transparent, preferably a transparent plastic, so the collection needle can be guided visually during insertion and removal. In a biopsy gun version with automated functioning, the vessel may be opaque, since the operator will rely on guides and mechanisms to determine the perforation orientation and movement distances at any stage.

The vessel may be filled with culture medium or another liquid before the last seal is applied. This can/should be done in a sterile, contaminant free fashion. To empty the vessel after removal from the collection needle, for example in a laboratory, the seal may be pulled out or removed by unscrewing, depending on the actual construction, or the vessel itself may be breakable, similarly to a breakable ampoule. The removal of the seal is preferred to a breakable version of the vessel.

The vessel may also be filled after applying the seals through the seals themselves, preferably through a preformed through orifice as described above.

The vessel may also be provided with a luer fitting for leak-free filling after the seals are applied. The luer can be mounted on any outer surface of the vessel, but preferably not on the seals themselves, even if this is indeed possible. A luer on the seal could be more easily accomplished on the non-distal (proximal) end of the vessel.

The vessel may be provided with a skin seal, which is ring-like, of a rectangular, square or O section or a lip like structure placed or formed either on the end of the vessel that is closer to the animal’s skin (when the vessel seal is placed completely inside the inner diameter of the vessel) or placed or formed on the actual seal placed on the end of the vessel closer to the animal’s skin, that skin seal being appropriate to further seal the space between the animal’s skin and the vessel by creating an isolated space when the vessel and skin seal are pushed against the skin. Especially in the embodiment using a monolithic sheath, the skin seal may even help further maintain sterility when bringing the sheath back inside the vessel. Fig.6 shows an example of a skin seal directly formed on the distal side vessel seal, in this case a rectangular section ring protruding from the seal’s outer base, that should be pressed against the skin of the biopsied animal.

The vessel may be provided with anchoring means to the collecting needle.

Obviously, several different equivalents to all these vessel features may be thought of without recourse to further inventive activity, as long as the basic principle of the vessel being able to be traversed by a collection needle whilst keeping its watertightness is upheld.

The holding chamber

It may be desirable to, for example, perform the insertion of the collection needle at a different time as the biopsy. For example, the insertion of the collection needle may be performed in a controlled environment, such as a laboratory, and the biopsy executed later in the field, such as in a farm. To prevent contamination of the tip of the collection needle over time, a sterile holding chamber (71) may be provided for the tip of the collection needle after this is inserted through the two seals of the collection vessel as seen in fig.7. The holding chamber is formed by a holding chamber part (72), which roughly presents as a hollow cone or hemisphere, that, at its base, may be attached to the collection vessel or the distal side seal, or even formed as part of the collection vessel or the distal side seal, the holding chamber presenting with an holding chamber orifice (74) that will allow the collection needle to exit the holding chamber during use in the actual biopsy. The holding chamber orifice is covered by a holding chamber cover (73) to maintain the interior of the chamber sterile or at least isolated from the external environment. At the moment of taking the biopsy, as the full device approaches the skin of the animal, the distal end of the holding chamber eventually makes contact with the skin. At this point, the holding chamber cover may be pulled out or detached using a pulling tab or similar, leaving the chamber hole free to be traversed by the collection needle to perform the biopsy. In the specific embodiment shown in fig.7 the holding chamber cover 73 is shaped like a pull out tab guided in a slot formed in the holding chamber part but this cover may also be a simple sticker over the hole with no guiding slot. In a demonstration of the spirit of combination of embodiments, fig. 7 shows an example of an holding chamber part presenting with a skin seal formed on the part itself (61a). This specific embodiment is probably the most sterile of all, as the tip of the collection needle stays in the holding chamber until use, the materials adjacent to the collection chamber hole do not touch the skin of the animal and the holding chamber cover may be pulled out only after skin seal 61a is in full contact with the skin of the animal to be biopsied.

The holding chamber part may be made of a polymer or metal alloy, for example.

Claims

1. A biopsy device adapted to transfer a biological sample into a liquid with no transfer steps external to the biopsy device, comprising an inline collection vessel (10) and a collection needle characterized by the collection vessel having a seal (11) on each extremity and being mounted on the collection needle, the collection needle traversing the collection vessel in a straight line and the collection vessel comprising an internal cavity adapted to receive a biological sample, the internal cavity being pre-filled with a liquid, preferably cell culture medium.

2. A biopsy device according to claim 1 wherein the collection vessel comprises two perforable seals (11), the perforable seals optionally comprising two pre-made orifices.

3. A biopsy device according to claim 2 wherein the collection needle comprises an internal needle (12) with a collection cavity (13) and a monolithic (20) or notched (21) sheath, concentric to and on the outside of the internal needle (12).

4. A biopsy device according to claim 3 wherein the notched (21) sheath comprises a notch (22) of a size not smaller than required to expose the collection cavity (13) when this is aligned with the notch and wherein the notched sheath may optionally display alignment markings to determine the position of the collection vessel (10) in relation to the notch (22).

5. A biopsy device according to claim 3 or 4 wherein the collection vessel is contained within the body of a biopsy gun, configured to be able to open and close to insert and remove the collection vessel.

6. A biopsy device according to claim 5 wherein the collection needle is supported by mechanical supports built on the body of the gun, the mechanical supports built in line with the collection vessel seals (11) to allow guiding the collection needle through the seals.

7. A biological sample inline collection vessel (10) for a biopsy device as claimed on claim 1, comprising two seals (11) on opposite sides, able to be traversed by a biopsy collection needle.

8. A vessel according to claim 7 wherein the seals comprise a screwed or forced in plug or membrane.

9. A vessel according to claim 8 wherein the plug or membrane optionally comprises a premade orifice of a dimension that allows self-sealing.

10. A vessel according to claim 9 wherein the vessel is opaque or transparent, wherein the vessel is preferably made of metal, glass or polymeric material.

11. A vessel according to claim 10 wherein a skin seal is placed or formed either on an end of the vessel or placed or formed on one of the seals, the side of the vessel or the seal being the one closest to the distal end of the collection needle.

12. A vessel according to claim 11 wherein the vessel comprises securing means to the collection needle, such as mechanical anchors.

13. A vessel according to any of claims 7 through 12 wherein a holding chamber (71) is formed at the distal end of the vessel or on the outside of the distal seal, by a holding chamber part (72) comprising an orifice (74) and a cover (73) for the orifice (74).

14. A vessel according to any of claims 7 through 13 wherein a bellows (24) is mounted in a connecting fashion between the collection vessel and the sheath, on one or both sides of the vessel, or between a collection vessel seal and the sheath, on one or both seals of the collection vessel.