GB2624193A

GB2624193A - Bioreactor

Info

Publication number: GB2624193A
Application number: GB2216700.1A
Authority: GB
Inventors: Singh Bhumika; David Hallam Vivian; Malcolm Wilkinson John
Original assignee: KIRKSTALL Ltd
Current assignee: KIRKSTALL Ltd
Priority date: 2022-11-09
Filing date: 2022-11-09
Publication date: 2024-05-15
Also published as: GB202216700D0

Abstract

A bioreactor body 102 has a bottom face 108 for sealing onto a microscope slide 138 and an opposed top end 110 for receiving a bioreactor lid 104. The body is hollow with a cavity 106B opening at the bottom face and top end and extending through the body. The cavity is surrounded by a wall 112 with an inner surface, and an inlet 114 and outlet 116 for fluid communication into and out of the cavity extend through the wall. The inner surface of the wall is provided with an interior seal 124 that extends around the cavity, and/or a ledge or shelf 118 projects into the cavity from the inner surface for supporting a sample carrying member 190 inserted from the top end of the body. A bioreactor lid for releasably sealing an open top end of the bioreactor body has a peripheral wall extending around a lid top, and a central axis. A lid inlet and lid outlet are provided through the peripheral wall and open into the interior of the lid through respective lid inlet and outlet bores. At least the lid inlet bore is angled away from the central axis by at least 30º.

Description

BIOREACTOR

TECHNICAL FIELD

The present application relates to bioreactors for growing live cells that are supplied with a flow of fluid, which may carry nutrients for cell growth.

BACKGROUND

Bioreactors are used for the growth of live cells upon removable membranes. Problems exist with sealing membranes between two different fluids, the consistent positioning of the membranes within the chamber, ease of insertion and removal of the membranes, and the circulation of fluid across the membrane when spaced apart from the corresponding fluid inlet.

SUMMARY OF THE DISCLOSURE

According to a first aspect, there is provided a bioreactor body, wherein the bioreactor body has a bottom face for sealing onto a microscope slide and an opposed top end for receiving a bioreactor lid, the bioreactor body is hollow with a cavity opening at the bottom face and the top end and extending through the bioreactor body, the cavity is surrounded by a bioreactor body wall with an inner surface, the bioreactor has a body inlet and a body outlet for fluid communication into and out of the cavity through the bioreactor body wall, and the cavity is surrounded by a bioreactor body wall with an inner surface, and the inner surface of the bioreactor body wall is provided with an interior seal that extends around the cavity.

According to a second aspect, there is provided a bioreactor body, wherein the body has a bottom face for sealing onto a microscope slide and an opposed top end for receiving a bioreactor lid, the bioreactor body is hollow with a cavity opening at the bottom face and the top end and extending through the bioreactor body, the cavity is surrounded by a bioreactor body wall with an inner surface, the bioreactor has a body inlet and a body outlet for fluid communication into and out of the cavity through the bioreactor body wall, and a ledge or shelf projects into the cavity from the inner surface of the bioreactor body wall for supporting the base of a sample carrying member inserted into the cavity from the top end onto a standing surface of the ledge or shelf.

According to a third aspect, there is provided a bioreactor body array comprising a plurality of integrally formed bioreactor bodies according to the first or second aspect.

According to a fourth aspect, there is provided a bioreactor chamber comprising a bioreactor body according to the first or second aspect and a bioreactor lid, or a bioreactor chamber array comprising a bioreactor body array according to the third aspect wherein each bioreactor body is provided with a bioreactor lid.

According to a fifth aspect, there is provided a bioreactor lid for receiving and releasably sealing an open top end of a bioreactor body, the bioreactor lid having peripheral wall extending around a lid top, the bioreactor lid having a central axis, wherein a lid inlet and a lid outlet are provided through the peripheral wall and open into the interior of the bioreactor lid through a respective lid inlet bore and lid outlet bore, and at least the lid inlet bore is angled away from the central axis by at least 300.

The interior seal may be an elastomeric ring projecting into the cavity from a channel extending around the inner surface of the bioreactor body wall.

The interior seal may be a lip seal extending around the inner surface of the bioreactor body wall.

The interior seal may comprise a resiliently deformable member formed on the inner surface of the bioreactor body wall or formed in a channel extending around the inner surface of the bioreactor body wall and projecting from the bioreactor body wall into the cavity.

The body inlet and the body outlet may be provided through the bioreactor body wall proximate the bottom face of the bioreactor body, and the interior seal may be provided on the opposite side of the body inlet and body outlet from the bottom face of the bioreactor body.

The cavity may be wider adjacent the top end than adjacent the interior seal, and the cavity may have a tapered section between the top end and the interior seal.

The body inlet and a body outlet may be provided through the bioreactor body wall proximate the bottom face of the bioreactor body, and the body outlet may open into the cavity through an outlet aperture, and the furthest part of the outlet aperture from the bottom face of the bioreactor may be further from the bottom face of the bioreactor than the separation between standing surface of the ledge or shelf and the bottom face of the bioreactor.

The furthest part of the outlet aperture from the bottom face of the bioreactor may be further from the bottom face of the bioreactor than the separation between standing surface of the ledge or shelf and the bottom face of the bioreactor by at least 1 mm.

The ledge or shelf may comprise standing shelf sections 118A separated at each end by a gap adjacent the fluid inlet and the fluid outlet.

The ledge or shelf may be an annular ledge or shelf that extends all of the way around the inner surface of the bioreactor body wall.

Adjacent the top end, a ledge may project into the cavity from the inner surface of the wall for suspending an upper lip or suspension bracket of a sample carrying member inserted into the cavity from the top end.

In or adjacent the top end, rebates may be provided into the wall for receiving suspension brackets of a sample carrying member inserted into the cavity from the top end.

The outer surface of the bioreactor body wall may be provided with an exterior seal that extends around the bioreactor body proximate the top end for forming a fluid seal with a bioreactor lid.

The exterior seal may be an elastomeric ring projecting from a channel extending around the outer surface of the bioreactor body wall.

The outer surface of the exterior of the bioreactor body may be narrower adjacent the top end than adjacent the exterior seal, and the bioreactor body may have a tapered section between the top end and the exterior seal The bottom face may be provided with an adhesive layer for sealing onto a microscope slide.

The body inlet and the body outlet may respectively open into the cavity through a flared inlet and a flared outlet.

The body inlet of one bioreactor body of the bioreactor body array may be coupled to the body outlet of an adjacent bioreactor body.

The lid outlet bore may be angled away from the central axis by at least 300.

The lid inlet bore and lid outlet bore may be at least partially aligned with the lid top, and the internal face of the lid top is provided with a flow enhancement recess extending from each of the lid inlet bore and the lid outlet bore.

DESCRIPTION OF THE DRAWINGS

Examples are further described hereinafter with reference to the accompanying drawings, in which: * Figure 1A shows a cross-sectional view of bioreactor having a bioreactor body and a bioreactor lid with a standing bioreactor insert; * Figure 1B shows a cut-away view of a bioreactor body array having a plurality of integrally formed bioreactor bodies; * Figure 10 shows a plan view of a bioreactor body from above; * Figure 10 shows a cross-sectional view of bioreactor body array having a plurality of bioreactor bodies and a bioreactor lid with a suspended bioreactor insert; * Figure lE shows a cut-away view of a further bioreactor body; * Figure 1F shows a cross-sectional view of the further bioreactor body of Figure lE with a standing bioreactor insert; * Figure 1G shows an isometric view of the underside of the bioreactor body; * Figure 1H shows an enlarged plan view of part of the underside of the bioreactor body; * Figure 2A shows a bioreactor body array having a plurality of integrally formed bioreactor bodies, in which the lower chambers of successive chamber bodies are coupled in series; * Figure 2B shows a view of the bioreactor body array of Figure 2A from above; * Figure 2C shows a second bioreactor body array having a plurality of integrally formed bioreactor bodies, in which the lower chambers each have a fluid inlet and fluid outlet for coupling to the exterior; * Figure 20 shows a third bioreactor body array having a plurality of integrally formed bioreactor bodies, in which the lower chambers have no fluid inlet or fluid outlet; * Figures 3A and 3B shows views of a further bioreactor lid; * Figure 30 shows a view of the underside of the further bioreactor lid; and * Figure 3D shows a view of a bioreactor array having a bioreactor body array with a bioreactor lid on each bioreactor body.

DETAILED DESCRIPTION

In the described examples, like features have been identified with like numerals, albeit in some cases having one or more of: increments of integer multiples of 100; suffix letters; and typographical marks (e.g. primes, asterisks and daggers). For example, in different figures, 102, 102', 102", 102-, 102A, 102B, and 1020 have been used to indicate a bioreactor body.

Figure 1A shows a cross-sectional view of a bioreactor 100 having a bioreactor body 102 and a bioreactor lid 104. Figure 13 shows a cut-away view of a bioreactor body array 142 having a plurality of bioreactor bodies 102A, 102B, 1020 corresponding to the bioreactor body 102 of Figure 1B.

The bioreactor body 102 has a cavity 106 extending between an opening at the bottom (bottom face) 108 and an opening at the top (top face) 110 of the bioreactor body. The cavity 106 is surrounded by the wall 112 of the bioreactor body 102. A fluid inlet 114 and fluid outlet 116 extend through the wall 112 of the bioreactor body 102, close to the bottom 108.

The bioreactor body 102 is adapted to receive a bioreactor chamber insert 190 into the cavity 106 through the opening in the top 110. The insert 190 has a membrane 192 for supporting live cells, which partitions the cavity 106 into a lower chamber 106A beneath the membrane and an upper chamber 1068 above the membrane. The fluid inlet 114 and fluid outlet 116 couple into the lower chamber 106A (i.e. are in direct fluid communication) for supplying a flow of fluid through the lower chamber 106A and to the underside of the membrane 192, in use.

The internal surface of the wall 112 of the bioreactor body 102, close to the fluid inlet 114 and fluid outlet 116, is provided with a standing shelf 118 for bioreactor chamber inserts 190 to stand upon, as shown in the cut-away view of Figure 1B, and in the plan view of Figure 10. By standing upon the standing shelf 118, as shown in Figure 1A, different inserts 190 may be positioned within the cavity 106 with their membranes 192 at the same height above the underlying surface 138, facilitating the provision of identical growth conditions in different bioreactors 100. Consistent positioning of the insert membranes 192 within the cavity 106 of the bioreactor 100 enables cells to be grown on the membranes of different bioreactor inserts with consistent hydrodynamic properties (e.g. with consistent sheer forces of liquid flowing through the lower chamber 106A, and with a consistent differential pressure across the membrane).

The standing shelf 118 in the bioreactor body 102 shown in Figures 1B and 10 is formed in two standing shelf sections 118A, separated at each end by a gap at the fluid inlet 114 and the fluid outlet 116. The gaps in the standing shelf 118 reduce hydrodynamic resistance into and out of the lower chamber 106A.

Figures 1E and 1F show a further bioreactor body 102', in which the standing shelf 118' extends all of the way around the internal surface of the wall 112 of the bioreactor body, forming an annular standing shelf. (The internal seal 124 and external seal 130 have not been shown in Figure 1E.) The standing shelf 118' is provided with standing shelf bridges 118B' that extend past the fluid inlet 114 and the fluid outlet 116 whilst enabling fluid flow both above and below the standing shelf bridges.

Providing the standing shelf 118' that extends all of the way around the internal surface of the wall 112 of the bioreactor body 102' facilitates the use of bioreactor chamber inserts 190 with insert feet 190F that extend from their bottom surfaces. The annular standing shelf 118' enables the insertion of the bioreactor chamber insert in all rotational orientations, by avoiding the risk of aligning an insert foot at a gap between the standing shelf sections (118A in Figure 1B), resulting in instability in the positioning of the bioreactor chamber insert 190 and the alignment of the bioreactor membrane 192.

At the top 110 of the cavity 106, the wall 112 of the bioreactor body 102 is optionally provided with a suspension ledge 120 for supporting alternative bioreactor chamber inserts 190' that are hung down into the cavity, as shown in Figure 1D. At the top 110 of the cavity 106, the wall 112 of the bioreactor body 102 is optionally provided with suspension rebates 122, as shown in Figure 1B, which are for receiving hanging tabs projecting radially outwardly around the top of a further design of bioreactor chamber inserts 190'. The provision of one or both of the suspension ledge 120 and the suspension rebates 122 enables bioreactor inserts 190' to be suspended within cavity 106 with their membranes 192' at the same height, whilst enabling the upper chamber 106B to be closed by the bioreactor lid 104. Consistent positioning of the insert membranes 192' within the cavity 106 of the bioreactor 100 enables cells to be grown on the membranes of different suspended bioreactor inserts 190' with consistent hydrodynamic properties.

An internal seal 124 is provided, extending around the internal surface of the wall 112 of the bioreactor body 102 for sealing around the external surface of an insert 190, 190' standing within or suspended within the cavity 106. Sealing between the internal seal 124 and the insert 192 enables cells to be grown on the membrane with different fluids in the lower chamber 106A and the upper chamber 106B, e.g. liquid in the lower chamber and gas in the upper chamber, or two different liquids in the lower and upper chambers. The seal between the insert 190, 190' and the chamber wall 112 enables the insert to be held in position to prevent the insert from rising (e.g. floating) whilst also preventing fluid in the lower chamber from passing around the outside of the insert and into the upper chamber. Being sealed enables the bioreactor chamber 100 to be used to grow cells on the membrane 192, 192' at an interface between different fluids in the lower and upper chambers 106A, 106B, for example having liquid in the lower chamber and gas in the upper chamber.

The illustrated internal seal 124 is formed by an elastomeric ring ("0-ring") partially recessed into a channel 126 extending around the wall 112 of the bioreactor body 102. The bioreactor body 102 may be formed by moulding, and the channel 126 may be formed during the moulding process, with the elastomeric ring 124 being fitted into the channel after the moulding process.

The bioreactor body 102 may be provided with an alternative external seal for sealing against the exterior of the bioreactor insert 190, 190', for example being provided with a lip seal (rotary shaft seal). Alternatively, the internal seal may be formed by co-moulding with the wall 112 of the bioreactor body 102.

The bores of the fluid inlet 114 and fluid outlet 116 are both close to the bottom 108 of the bioreactor body 102 (e.g. the bores are coaxial), and the internal seal 124 is also provided towards the bottom 108 of the bioreactor body 102, above the bores of the fluid inlet and fluid outlet.

The standing ledge 118 is lower than the top of the bores of the fluid inlet 114 and fluid outlet 116, e.g. at least 1mm lower. This positioning enables the membrane 192 of a bioreactor insert 190, 190' to be beneath the level top of the bores of the fluid inlet and fluid outlet, which reduces or prevents the risk of gas bubbles being retained on the under-surface of the membrane, when the lower chamber 106A is filled with liquid.

The inner face of the wall 112 of the bioreactor body 102 extends around the cavity 106, which is wider at the top 110 than at the internal seal 124. The inner face of the wall 112 has a tapered portion 128 above the internal seal 124, which tapers inwardly towards the internal seal. Providing the tapered portion 128 of the inner face of the wall 112 guides the base of the insert into position within the cavity 106 during insertion of inserts 190, 190'. In the case of bioreactor inserts 190 standing upon the standing shelf 118, the tapered portion 128 facilitates insertion and removal of the insert by providing clearance around the top of the insert for grasping the insert with tweezers (or an alternative insertion and removal tool). The tapered portion 128 also provides a sufficient volume of space around the exterior of the inserts 190, 190' to reduce the pooling of stagnant fluid within the upper chamber 106B.

An external seal 130 is provided, close to the top 110, extending around the external surface of the wall 112 of the bioreactor body 102 for sealing with the internal surface of the bioreactor lid 104, enabling the upper chamber 106B to be sealed between the internal seal 124 and the external seal 130.

The illustrated external seal 130 is formed by an elastomeric ring ("O-ring") partially recessed into a channel 132 extending around the wall 112. The bioreactor body 102 may be formed by moulding, and the channel 132 may be formed during the moulding process, with the elastomeric ring 130 being fitted into the channel after the moulding process.

The bioreactor body 102 may be provided with an alternative internal seal for sealing against the interior of the bioreactor insert lid 104, for example being provided with a lip seal (rotary shaft seal). Alternatively, the external seal may be formed by co-moulding with the wall 112 of the bioreactor body 102.

The internal seal 124 and the external seal 130 may be formed from elastomers including FKM, ACM, NBR, HN BR, and AEM. In order to resist wear, the durometer hardness of the internal seal 124 and the external seal 130 may be 50 to 85 Shore A. The external face of the bioreactor wall 112 has a tapered portion 134 above and adjacent the external seal 132, tapering inwardly towards the top 110 of the bioreactor body. Being narrower at the top 110 than adjacent the external seal 132, and being tapered above and adjacent the external seal 132, facilitates fitting the bioreactor lid 104 onto the bioreactor body 102, whilst reducing the risk of damaging the external seal with the inner edge of the lid.

The bottom face 108 of the bioreactor body 102 is (optionally) provided with a ring of adhesive 136 (shown only in Figure 1A) for sealing onto an underlying surface, e.g. a microscope slide 138. The bioreactor body 102 may be provided with a protective cover layer (not shown) covering the adhesive 136, which is peeled off before the bioreactor body is adhered to the underlying surface 138.

Figure 1G shows an isometric view of the underside of the bioreactor body 102 of Figure 1A. Figure 1H shows an enlarged plan view of part of the underside of the bioreactor body 102. Adjacent the fluid inlet 114 and the fluid outlet 116, the lower chamber 106A is flared 140, to reduce turbulence arising in fluid flow F into and out of the lower chamber.

The fluid inlet 114 and fluid outlet 116 to each bioreactor body 102 is provided with a fluid coupling 146 to which a flexible hose (not shown) may be connected, in use.

A single bioreactor body 102 may be provided, as shown in Figure 1A. Alternatively, a plurality of bioreactor bodies 102A, 102B, 102C may be integrally formed as a bioreactor body array 142 as shown in Figures 2A and 2B, in which the lower chambers 106A of successive chamber bodies 102A, 102B, 1020 are coupled in series, with the fluid outlet 116 of one cavity 106 being coupled to the fluid inlet 114 of the next chamber body. The successive chamber bodies 102A, 102B, 102C of the bioreactor body array 142 may connected together by a common base 144, as shown in Figure 2B. The fluid inlet and fluid outlet to the serially coupled array of bioreactor bodies 102A, 102B, 102C are each provided with a fluid coupling 146 to which a flexible hose 148 may be connected.

In a further alternative, a plurality of bioreactor bodies 102" may be integrally formed as a bioreactor body array 142", as shown in Figure 20, in which the lower chambers 106A of successive chamber bodies are each provided with a fluid inlet 114 and a fluid outlet 116 coupling to the exterior, e.g. through a fluid coupling 146 to which a flexible hose may be connected. Integrally forming the plurality of independently coupled bioreactor bodies 102" provides the bioreactor bodies in a format that is easy to handle and with a small footprint, which may be convenient when multiple samples are grown in bioreactors coupled in parallel to supply fluids.

In a yet further alternative, a plurality of bioreactor bodies 102" may be integrally formed as a bioreactor body array 142", as shown in Figure 2D, in which in which the lower chambers 106A have no fluid inlet or fluid outlet. Coupling may be between the upper chambers 106B of the bioreactor bodies 102" may be provided through ports in their lids 104', in use.

Similarly to the bioreactor bodies 102" in Figure 2D, individual bioreactor bodies may be formed with no fluid inlet or fluid outlet to the lower chamber. Coupling to the upper chamber of the bioreactor body may be provided through ports in its lid 104', in use As shown in Figure 1A, the bioreactor 100 may have a bioreactor lid 104 that provides a releasably seals to the bioreactor body 102 to provide a closure to the open top 110 of the cavity 106 of the bioreactor body. Similarly, each bioreactor body of a bioreactor body array 142 may be provided with a bioreactor lid 104.

As shown in Figures 3A to 3D, the bioreactor lid 104' may additionally be provided with a lid inlet 152 and lid outlet 154 for fluid to flow through the upper chamber 106B of the bioreactor 100, e.g. providing a gas flow through the upper chamber.

At least the lid inlet 152, and optionally also the lid outlet 154, may have a bore that is non-radially orientated, with respect to a centreline C (also shown in Figure 1A) of the cavity 106 of the bioreactor body 102. As shown in Figure 3A, where the bore of the lid inlet 152 extends into the upper chamber 106B, the bore is angled away from the centre of the lid, e.g. being angled away by an angle 156 of at least 300. By the bore of the lid inlet 152 being angled non-radially, fluid flowing into the upper chamber 106B through the lid inlet causes fluid within the upper chamber to form a vortex, enhancing the circulation of fluid across the upper surface of the membrane 192, 192' of the bioreactor insert 190, 190', and reducing the risk of a stagnant pocket of fluid remaining in the bottom of the upper chamber adjacent the membrane.

Similarly, where the bore of the lid outlet 154 extends into the upper chamber 106A, the bore may also be angled away from the centre of the lid, e.g. being angled away by an angle 156 of at least 30°. Non-radial angling of the bore of the lid outlet 154 may further enhance circulation of fluid in the bottom of the upper chamber 106B.

The bores of the lid inlet 152 and the lid outlet 154 may extend perpendicular to the centreline C of the bioreactor cavity 106B, which may be parallel to the top member 158 (e.g. a sheet of material) of the bioreactor lid 104, 104'.

The top member 158 may be optically transparent had have optically flat inner and outer surfaces, enabling samples within the cavity 106 to be viewed through the lid 104, 104' with a microscope.

The bores of the lid inlet 152 and lid outlet 154 pass through the peripheral wall 160 of the bioreactor lid 104, 104', and may overlap with the top member 158 of the bioreactor lid. Adjacent the lid inlet 152 and lid outlet 154, the underside of the top member 158 of the bioreactor lid 104, 104' may be provided with fluid flow grooves 162 (flow enhancement recesses) extending away from the peripheral wall. The provision of the fluid flow grooves 162 enables the lid inlet 152 and lid outlet 154 to overlap with the top member 158, whilst maintaining good fluid flow through the lid inlet and lid outlet, which enables the lid to be more compact, reducing the height of the assembled bioreactor 100.

When used with a bioreactor body array 142, as shown in Figure 3D, non-radial angling of the bores of both the lid inlet 152 and the lid outlet 154 may simplify the connection of fluid hoses to the lid inlets and lid outlets, and may enable the bioreactor bodies 102A, 102B, 102C to be more closely spaced, providing a more compact bioreactor array.

Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of them mean "including but not limited to", and they are not intended to (and do not) exclude other moieties, additives, components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

The reader's attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

Claims

CLAIMS1. A bioreactor body, wherein the bioreactor body has a bottom face for sealing onto a microscope slide and an opposed top end for receiving a bioreactor lid, the bioreactor body is hollow with a cavity opening at the bottom face and the top end and extending through the bioreactor body, the cavity is surrounded by a bioreactor body wall with an inner surface, the bioreactor has a body inlet and a body outlet for fluid communication into and out of the cavity through the bioreactor body wall, and the cavity is surrounded by a bioreactor body wall with an inner surface, and the inner surface of the bioreactor body wall is provided with an interior seal that extends around the cavity.
2. The bioreactor body according to claim 1, wherein the interior seal is an elastomeric ring projecting into the cavity from a channel extending around the inner surface of the bioreactor body wall.
3. The bioreactor body according to claim 1, wherein the interior seal is a lip seal extending around the inner surface of the bioreactor body wall.
4. The bioreactor body according to claim 1, wherein the interior seal comprises a resiliently deformable member formed on the inner surface of the bioreactor body wall or formed in a channel extending around the inner surface of the bioreactor body wall and projecting from the bioreactor body wall into the cavity.
5. The bioreactor body according to any preceding claim, wherein the body inlet and the body outlet are provided through the bioreactor body wall proximate the bottom face of the bioreactor body, and the interior seal is provided on the opposite side of the body inlet and body outlet from the bottom face of the bioreactor body.
6. The bioreactor body according to any preceding claim wherein the cavity is wider adjacent the top end than adjacent the interior seal, and the cavity has a tapered section between the top end and the interior seal.
7. A bioreactor body, wherein the body has a bottom face for sealing onto a microscope slide and an opposed top end for receiving a bioreactor lid, the bioreactor body is hollow with a cavity opening at the bottom face and the top end and extending through the bioreactor body, the cavity is surrounded by a bioreactor body wall with an inner surface, the bioreactor has a body inlet and a body outlet for fluid communication into and out of the cavity through the bioreactor body wall, and a ledge or shelf projects into the cavity from the inner surface of the bioreactor body wall for supporting the base of a sample carrying member inserted into the cavity from the top end onto a standing surface of the ledge or shelf.
8. The bioreactor body according to claim 7, wherein the body inlet and a body outlet are provided through the bioreactor body wall proximate the bottom face of the bioreactor body, and the body outlet opens into the cavity through an outlet aperture, and the furthest part of the outlet aperture from the bottom face of the bioreactor is further from the bottom face of the bioreactor than the separation between standing surface of the ledge or shelf and the bottom face of the bioreactor.
9. The bioreactor body according to claim 8, wherein the furthest part of the outlet aperture from the bottom face of the bioreactor is further from the bottom face of the bioreactor than the separation between standing surface of the ledge or shelf and the bottom face of the bioreactor by at least 1 mm.
10. The bioreactor body according to claim 8 or claim 9, wherein the ledge or shelf comprises standing shelf sections 118A separated at each end by a gap adjacent the fluid inlet and the fluid outlet.11. The bioreactor body according to claim 8 or claim 9, wherein the ledge or shelf is an annular ledge or shelf that extends all of the way around the inner surface of the bioreactor body wall.10. The bioreactor body according to any one of claims 7, Band 9, wherein adjacent the top end, a ledge projects into the cavity from the inner surface of the wall for suspending an upper lip or suspension bracket of a sample carrying member inserted into the cavity from the top end.
11. The bioreactor body according to any one of claims 7 to 10, wherein in or adjacent the top end, rebates are provided into the wall for receiving suspension brackets of a sample carrying member inserted into the cavity from the top end.
12. The bioreactor body according to any preceding claim, wherein the outer surface of the bioreactor body wall is provided with an exterior seal that extends around the bioreactor body proximate the top end for forming a fluid seal with a bioreactor lid.
13. The bioreactor body according to claim 12, wherein the exterior seal is an elastomeric ring projecting from a channel extending around the outer surface of the bioreactor body wall.
14. The bioreactor body according to claim 12 or claim 13, wherein the outer surface of the exterior of the bioreactor body is narrower adjacent the top end than adjacent the exterior seal, and the bioreactor body has a tapered section between the top end and the exterior seal.
15. The bioreactor body according to any preceding claim, wherein the bottom face is provided with an adhesive layer for sealing onto a microscope slide.
16. The bioreactor body according to any preceding claim, wherein the body inlet and the body outlet respectively open into the cavity through a flared inlet and a flared outlet.
17. A bioreactor body array comprising a plurality of integrally formed bioreactor bodies according to any preceding claim. 20 18. A bioreactor body array according to claim 17, wherein the body inlet of one bioreactor body is coupled to the body outlet of an adjacent bioreactor body.
18. A bioreactor chamber comprising a bioreactor body according to any one of claims 1 to 16 and a bioreactor lid, or a bioreactor chamber array comprising a bioreactor body array according to claim 17 wherein each bioreactor body is provided with a bioreactor lid.
19. A bioreactor lid for receiving and releasably sealing an open top end of a bioreactor body, the bioreactor lid having peripheral wall extending around a lid top, the bioreactor lid having a central axis, wherein a lid inlet and a lid outlet are provided through the peripheral wall and open into the interior of the bioreactor lid through a respective lid inlet bore and lid outlet bore, and at least the lid inlet bore is angled away from the central axis by at least 30°.
20. A bioreactor lid according to claim 19, wherein the lid outlet bore is angled away from the central axis by at least 300.
21. A bioreactor lid according to claim 19 or claim 20, wherein the lid inlet bore and lid outlet bore are at least partially aligned with the lid top, and the internal face of the lid top is provided with a flow enhancement recess extending from each of the lid inlet bore and the lid outlet bore.