GB1598149A

GB1598149A - Blood oxygenator

Info

Publication number: GB1598149A
Application number: GB8369/78A
Authority: GB
Original assignee: Bramson M L
Current assignee: Bramson M L
Priority date: 1977-03-07
Filing date: 1978-03-02
Publication date: 1981-09-16
Also published as: CA1127490A; BR7801375A; IL54202A0; DE2809516A1; FR2382899A1; FR2382899B1; IT7820955A0; IT1110463B

Description

(54) BLOOD OXYGENATOR (71) I, MOGENS LOUIS BRAMSON, a citizen of the United States of America, of 35-21St Avenue, San Francisco, California 94121, United States of America, do hereby declare the invention, for which I pray that a patent may be granted to me, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to blood oxygenators of the membrane type wherein a semipermeable membrane separates the blood from the oxygen, oxygen passes through the membrane into the blood and carbon dioxide passes from the blood through the membrane into the stream of oxygen. Alternatively an aqueous solution of hydrogen peroxide may be used instead of oxygen gas, and the hydrogen peroxide then diffuses into the membrane, is broken down into oxygen and water by a catalyst and the oxygen passes into the blood. By "semi-permeable membrane" is meant, in the case where oxygen gas is employed, a membrane which is permeable to gas but impermeable to water.

Where a solution of hydrogen peroxide is used, the semi-permeable membrane is permeable to gas and water and to small solute molecules and ions but not to the larger components of blood such as red and white corpuscles and platelets.

Blood oxygenators used during open heart surgery to take over the function of the natural lungs are of several types, including the bubble type in which oxygen is bubbled through the blood in direct contact therewith, and the membrane type identified in the preceding paragraph.

Bubble type oxygenators are simpler and for that reason are widely used, but the trend is towards the membrane type of oxygenator.

The latter functions more nearly like the natural lung in that it separates the stream of oxygen from the blood and allows communication between the oxygen and the blood only by diffusion through a semi-permeable membrane. There is evidence that this more nearly natural functioning of membrane oxygenators is less harmful to the blood than that of bubble type oxygenators, especially during the course of lengthy (for example, five hours or more) open heart surgery.

However, membrane oxygenators heretofore have been much more complex than bubble oxygenators, so that as a practical matter they must be taken apart, cleaned, sterilized and reassembled with new membranes after each use. This is an expensive, time-consuming and cumbersome operation.

One such oxygenator is that described in my U.S. Patent No. 3,413,095, which has been very successful in use but suffers from the non-disposable characteristic described above.

In U.S. Patent No. 3,834,544 there is described a membrane type blood oxygenator which is intended to be of the disposable type, that is to say so inexpensive to manufacture that it can be used once and then discarded. However, to date that oxygenator has not been proved to be practicable in use, one of its defects being that it offers the possibility of inadvertent leakage of water fom the water circuit into the blood circuit.

Water leaking into the blood causes haemolysis and dilution and is harmful to the patient. Added to this drawback is the fact that inadvertent leakage of water from the water circuit into the blood circuit of a membrane oxygenator is not likely to become evident at once. This presents the possibility of inadvertent leakage of water from the water circuit into the blood circuit.

leakage is ascertained.

A further disadvantage of the membrane oxygenator of U.S. Patent No. 3,834,544 is the fact that to make and keep all fluid compartments leak-proof, it is necessary to employ cumbersome clamps to overcome structural problems which are described below.

It is the principal object of the invention to provide a disposable membrane-type blood oxygenator of simplified construction, such that it is economically feasible to employ the oxygenator once and once only and then discard it, such oxygenator being free of defects such as the possibility of leakage of water from the water circuit into the blood circuit.

The invention accordingly provides a blood oxygenator of the membrane type, which includes a set of blood, water and oxygen units disposed in stacked relationship and comprising at least one blood unit sandwiched between and adjacent to oxygen units, each said blood unit comprising a semi-permeable blood envelope equipped at each end with a plurality of blood flowthrough passages for the main flow of blood through the stack and for diverting a portion of such main flow of blood into the interior of the blood envelope for flow through said interior, each said water unit comprising a flexible water impermeable water envelope equipped at each end with a plurality of water flow-through passages for the main flow of water through the stack and for diverting a portion of such main flow of water into the water envelope for flow of water therethrough, the blood flow-through passages of the blood envelopes lying outside the perimeter of the water envelopes and the water flow-through passages of the water envelopes lying outside the perimeter of the blood envelopes, each oxygen unit occupying the space between a blood unit and a water unit or between two blood units and having an inlet and an outlet for flow of oxygen or hydrogen peroxide solution into, through and out of the oxygen unit, and the water and blood units being configured so as to form pathways extending through the stack, said pathways isolating the water flowthrough passages from the blood flowthrough passages so that if water leaks from a water flow-through passage such leakage will be routed by said pathways to an oxygen unit or to the exterior of the stack or to both rather than to a blood flow-through passage.

Certain embodiments of the invention are illustrated by way of example in the accompanying drawings, in which Figure 1 is a perspective view of an embodiment of the invention shown diagrammatically in its entirety and connected to sources of water and oxygen and to the circulatory system of a patient undergoing open heart surgery, Figure 2 is a largely diagrammatic, exploded perspective view showing the end plates in simplified form and showing a single blood unit, two oxygen units and two water units, Figure 3 is a plan view broken away to reveal portions of a blood unit, a water unit and an oxygen unit, Figure 4 is a section taken along the line 4--4 in Figure 3.

Figure 5 is a fragmentary perspective view of a blood unit, Figure 6 is a section taken along the line 6 6 in Figure 3, the end plates (which are shown for simplicity as simple blocks in Figures 1 and 2) being shown in reinforced form, Figure 7 is a fragmentary sectional view of one of the end plates showing a chamfer along an edge which serves a useful purpose as described below, Figure 8 is a fragmentary, exploded perspective view showing a water unit and an oxygen unit, a single component common to the water unit and the oxygen unit being shown, for clarity, as two separate components, Figure 9 is a perspective view showing an alternative and preferred form of end insert for the water units, such being also used for the oxygen units, Figure 10 is a fragmentary longitudinal section through a blood unit, Figure 11 is a fragmentary longitudinal section through an oxygen unit, Figure 12 is a fragmentary longitudinal view through a water unit, Figure 13 is a fragmentary transverse sectional view through a blood unit, Figure 14 is a plan view of an alternative form of water unit, Figure 15 is a plan view of an alternative form of oxygen unit, Figure 16 is a plan view of the screen for the oxygen unit shown in Figure 15, Figure 17 is a perspective view of the oxygen unit shown in Figure 15, Figure 18 is a section along the line 18-18 in Figure 17, Figure 19 is a section along the line 19-19 in Figure 15, Figure 20 is a section along the line 2-20 in Figure 14, Figure 21 is a view similar to Figure 7 but on a larger scale and showing more clearly the forces acting on the end plates and the stack of blood, oxygen and water units held together by the end plates, Figure 22 is a view similar to Figure 7 showing an alternative way of forming a chamfer, Figure 23 is a top plan view of an alternative embodiment of the invention showing the cover for the same, Figure 24 is a view in side elevation showing one side wall and showing edge views of the top and bottom covers and of the end walls, Figure 25 is an exploded view showing a blood unit with the upper membrane separated from the blood screen, other components of the blood unit and also a water unit sandwiched between two oxygen units, Figure 26 is a fragmentary horizontal section looking down upon one of the blood units, Figure 27 is a section taken along the line 27-27 in Figure 26 showing several water, oxygen and blood units in assembled condition and showing the means whereby water is introduced into the water units, Figure 28 is a section taken along the line 28-28 in Figure 26 showing the means whereby blood is introduced into the blood units Figure 29 is a section taken along the line 29-29 in Figure 26 showing the means whereby oxygen is introduced into the oxygen units, Figure 30 is a fragmentary plan view of an alternative water unit, Figure 31 is a section taken along the line 31-31 in Figure 30, and Figure 32 is a section taken along the line 32-32 in Figure 30.

The blood oxygenator 10 shown in Figure I comprises end plates 11 a and 11 b between which is a stack of water, oxygen and blood units collectively designated by the reference numeral 12, the whole assembly being held together by bolts 13 which pass through the end plates 11 a and 11 b and through the stack 12.

The blood oxygenator 10 is shown connected to certain external equipment which may be of well known design. Thus water and oxygen circulating and/or supply means are shown diagrammatically only at 14 and 15 respectively. The water supply 14 will include a pump and thermostatic means to effect circulation of the water and to maintain proper water and blood temperature and it may include a source of nitrogen under pressure to pressurize the water circuit. The oxygen supply 15 will comprise a source of oxygen under pressure and a suitable valving means, pressure' gauge and flow gauge. The blood inlet line 16a and blood outlet line 16b will be connected to the venous line and the arterial line from and to the patient, respectively, by suitable means which are well known in the art, and which include a pump in the venous line. U.S. Patent No. 3,413,095 describes suitable equipment of this type.

As shown in Figure 2, the end plate 11 a is formed on its inner surface with a long horizontal blood flow manifold 17, connected at one end to a blood inlet 18, and with short vertical slots 25 and 26 for water and oxygen outlets, respectively. The end plate 1 lib is similarly formed but is inverted with respect to the end plate l la. In Figures 1 and 2, the end plates l la and I lb are shown, for simplicity, as simple blocks but, preferably. they are constructed in another manner, for example as shown in Figures 6 and 7, and as described below. Between the end plates l la and l lb a simplified stack 12a is shown consisting of (reading from left to right) a water unit 26, an oxygen unit 27, a single blood unit 28, another oxygen unit 27 and another water unit 26. This simplified drawing serves the purpose of illustrating the flow of fluids (blood, water and oxygen) through the apparatus. In actual practice, the stack 12 will usually consist of a number of blood units sufficient to provide a total membrane surface adequate for oxygenating the patient's blood. In practice, a typical adult size preferred stack 12 should have the following stacking order, using the symbols W to indicate a water unit, 0 to indicate an oxygen unit and B to indicate a blood unit: W-O-B-O-B-O-W-O-B-O-B-O W-O-B-O-B-O-W-O-B-O-B-O W-O-B-O-B-O-W-O-B-O-B-O-W The assembly illustrated above has the advantage of using fewer water units W (one for each two blood units) and it therefore results in a more compact assembly of units, yet is sufficient to hold the thickness of the blood units (hence the depth of the blood path in the blood units) constant and equal to the thickness of the blood screens described below. However, for purposes of more adequate temperature control of the blood, a greater number of water units may be employed, for example, one water unit W for each blood unit B, thus W-O-B-O-W-O-B O-W-. That is, the module is -W-O-B-O-.

Figure 5 shows a blood unit 28 comprising a rectangular blood frame 30 including side members 31 and recessed end members 32 forming, with the side members, a recessed area 32a. This frame 30 is overlaid by a pair of membranes 33 which are permeable to gas (oxygen and carbon dioxide) but impermeable to liquid (blood and water). Within the blood space 33a between the membranes 33 is a screen 34. The membranes may be made of microporous polypropylene, microporous Teflon (Registered Trade Mark), silicone rubber or Teflon material in which the gases dissolve and diffuse. The screen 34 may be woven or extruded from polypropylene or polyester and may have a mesh of 18 to 22 counts per inch and a thickness (which determines the depth of the blood cavity 33a) of 0.020 inch.

The blood frame 30 is shown in three parts consisting of top and bottom parts (as viewed in Figure 5) 40 and 41 and an inner part 42.

Each of these parts is formed with longitudinal blood flow-through slots 43 along the side portions 31 and the inner part 42 is also formed with a series of transverse slots 44 extending from the respective slots 43 to the inner edge, and therefore to the blood space 33a. The flow-through slots 43 are in registry with one another to permit flow of blood through the assembly 12 (Figure 1), as well as out into the blood space, as will be described hereinafter. The frame members 40, 41 and 42 may be constructed of any suitable material having appropriate structural characteristics for the purpose and also be compatible with the fluids flowing in the system and capable of heat sealing to the membranes. A suitable material is polypropylene.

The membranes 33 are heat sealed at 46 to the frame along side members 31 and end members 32, thus forming a membrane envelope. As will be seen, the end members (of which only one is shown in Figure 5, there being another one at the other end) are imperforate.

A spacer 47 is received in the recess 32a at each end of the blood frame and it is formed with a pair of flow-through slots 48 extending therethrough, which are intended for the flow of oxygen and water as described hereinafter. As will be seen, the side parts 31 of the frame 30 and the insert 47 are provided with bolt holes 49, those in the side members 31 being outside the blood flow-through slots 43 and those in the spacer 47 lying outside the oxygen and water flow-through slots 48.

Referring now to Figure 8, a water unit 26 and an oxygen unit 27 are shown. This assembly of an oxygen unit and a water unit has a single side frame member 50 on each long side, which is common to both the water unit 26 and the oxygen unit 27. However, as explained above, the side member 50 is shown twice to show its relation to the water and oxygen units. As will be apparent, the water and oxygen units may, at particular places in the assembly 12 be W-O, or O-W O or 0 alone (i.e. not adjacent a water unit).

The thickness of the side member 50 will vary accordingly. The side members 50 are formed with blood flow-through slots 51 which register with slots 43 in the side members of the blood units.

A water mattress 52 is provided which is of water and gas-impermeable material, for example, flexible polyvinyl chloride, polypropylene, polyethylene or polyvinyl alcohol.

This material is sealed along all edges at 53, that is to say, two sheets of the material are seamed together as by heat sealing, vulcanizing or other suitable means. Instead of being formed from separate sheets and heat sealed, the water mattress may be formed from a seamless tube and heat sealed at the ends. In either case before the ends are sealed, the water mattress is fitted at each end with an insert 54 which, in the embodiment shown in Figure 8, is in three parts consisting of upper and lower parts 55 ("upper" and "lower" being used with reference to Figure 8, it being understood that in use the water, oxygen and blood units will be on edge) and a third or inner part 56. All of these components are slotted at 57-W (water flowthrough slots) and 57-0 (oxygen flowthrough slots), the water and oxygen slots registering with one another and providing water and oxygen flow-through passages, respectively. The water mattress is similarly slotted. The inner part 56 is also formed with a series of slots 58 which extend from the water flow-through slot 57-W inwardly to the edge of the insert, thereby connecting the slot 57-W with the interior of the water mattress.

The oxygen flow-through slot 57-0 in part 56 is free of such transverse slots.

Each end of the water mattress is fitted with such an insert, the two inserts being identical to one another but being inverted in relation to one another so that flow of water through the water mattress is diagonal, as indicated in Figure 2. Diagonal flow is advantageous because it minimizes channeling and enhances uniform water flow through the mattress.

Each end of an oxygen unit 27 is provided with an end insert 65 having projecting ears 66 which abut the side frame member 50 and which, together with the frame members forms an oxygen space 67 within which there is a screen 68. The screen 68 may be made of polypropylene or polyethylene or any of a number of weavable or extrudable plastics materials. Its overall thickness may be from 0.015 to 0.045 inch and the mesh of the weave may be 10 to 25 counts per inch.

Except for the configuration of its perimeter, the insert 65 is identical with the insert 54 described above with reference to the water unit. Similar parts are similarly numbered. The inner member 56 is formed with transverse slots 58 as in the case of the insert 54, but these slots connect with the oxygen flow-through slot 57-0 rather than the water flow-through slot 57-W. As in the case of the inserts 54 of the water unit, the insert 65 at one end of an oxygen unit is inverted in relation to the insert 65 at the other end, whereby the flow of oxygen through the oxygen unit is diagonal and uniform flow is enhanced.

Referring now to Figure 9, an alternative and preferred two-piece construction for the insert 54 is shown and it is generally designated by the reference numeral 70. It will be understood that although this depicts an insert for a water unit 26, the same construction may be employed for the end inserts 65 of an oxygen unit, with due allowance for the ears 66.

As shown in Figure 9, the insert 70 consists of a bottom (as viewed in Figure 9) piece 71 formed with transverse grooves 73 communicating with the water slot 57-W and a top piece 72. As in the case of the inserts 54 and 65, bolt holes 49 are provided which lie outside the slots 57-0 and 57-W.

A similar simplified construction may be employed for the blood frame 30, this being shown in Figure 13 in transverse section, and in Figure 10 in longitudinal section.

Referring to Figure 13, the frame has a side member 30a comprising a lower thick portion 80 and a thinner cover plate 81. The plate 80 is formed with a series of grooves, one such groove being shown at 82 and serving to provide blood flow from the blood flow-through slot 43. That is to say, in this construction the side members 30a are formed with grooves moulded in the lower portion 80 rather than having a third, comblike component such as shown at 42 in Figure 5. Also shown in Figure 13 are heat seals 83 between the membranes 33 and the frame members, and also a heat seal 84 between the cover plate 81 and the lower portion 80. Such heat seals extend around the entire perimeter of the blood frame.

From the description above, and with particular reference to Figure 2 (which, as stated, is a simplified arrangement of blood, oxygen and water units, but which will suffice for the purpose of illustrating the flow of fluids) it will be apparent that the flow paths of the three fluids (blood, water and oxygen) are as follows: Blood fills the manifold 17 in the end plate 11 a and flows through blood flow-through slots 51 in the adjacent water unit 26 and oxygen unit 27.

(As explained above, a single side member 50 bridges a pair of water and oxygen units, but for simplicity, each unit is shown with a separate side member 50). At the level of the blood unit 28 a portion of this stream of blood flows through slots 44 (see Figure 5), or through grooves 82 if the construction of Figure 13 is used, into the respective blood space 33a, thence to slots 44 (or grooves 82) on the opposite sides and then through the blood flow-through slots 51 to the groove 17 in the end plate l lb and thence to the arterial system of the patient. It will be understood that in actual practice where multiple blood units are employed rather than a single blood unit as in Figure 2, a portion of the blood will flow into each blood unit.

The flow of water and oxygen are opposite to the flow of blood in the sense that they enter through the end plate llb and leave through the end plate lla, whereas blood enters through the end plate l la and leaves through the end plate llb, but within the respective water and oxygen units 26 and 27 the flow is as shown in Figure 2, a portion of the flow of each fluid being diverted at the level of each respective water or oxygen unit for flow through that unit. It will be seen that the flow of blood and the flow of water are upwards. Thus at the level of each blood unit 28 that portion of the stream of blood which is diverted into such unit flows upwards into the blood space 33a. and at the level of each water unit 26 that portion of the stream of water which is diverted into such unit also flows in an upward direction. This aids in avoiding entrapment of air or other gas which is especially important in the case of the blood because such entrapment could cause an embolism.

In start up (after the water and blood units 26 and 28 have been tested and the completely assembled apparatus tested as described below) the apparatus is primed and in priming care is taken to remove all air or other gas from the blood and water circuits.

This is aided by the upward flow patterns noted above and shown in Figure 2 and it is also aided by tilting the apparatus (see Figure 1) so that the lower edge of the end plate 1 lea is lower than the lower edge of the end plate 11 b and so that the right-hand ends (as viewed in Figure 1) of the end plates are higher than their other ends. Therefore, the blood flow at all times has an upward component. Therefore when the apparatus is primed and ready for use, it is free of entrapped gas, and it remains free of gas during use. This is, as noted, especially important in the case of the blood circuit.

The apparatus is held, by suspension or otherwise, in the doubly tilted attitude (i.e.

tilted about one edge and about one end) during use.

As noted above, the end plates 1 la and 1 lb are shown in Figures 1 and 2 as rectangular prisms, but their preferred construction is otherwise. A suitable construction is shown by way of example in Figures 6 and 7. As will be seen from Figure 6, each of the end plates comprises a solid plate 90 of suitable material, for example polycarbonate, acrylic resin or acrylonitrile-butadiene-styrene resin. This plate is reinforced by longitudinal ribs 91 and lateral ribs 92. The entire construction may be moulded in one piece. Bolt holes are shown at 93 to receive the bolts 13. Referring now particularly to Figure 7, it will be seen that outer edge 94 is chamfered, the angle of the chamfer being typically about 1".

The chamfer surfaces 94 intersect the major, interior flat surface of the plate along fulcrum lines 94a which are located inwardly not only of the bolt holes 93 but also of the flow-through slots 43 and 48 (see Figure 8) and the blood flow manifolds (see Figure 2).

Therefore, as the bolts 13 are tightened the chamfered edges 94 (which extend around the entire periphery of the end plates) are pulled toward one another with the intersection of the chamfers and the flat central portions of the end plates acting as fulcrums.

When the water mattresses are filled with water under pressure, typically about 12 psi gauge, the water pressure also tends to force the chamfered edges of one plate toward those of the other plate. These forces in turn act on the edge portions of the stack 12 of blood, water and oxygen units, thereby ensuring more nearly uniform pressure intensity between the joint making contact surfaces in the periphery of the stack. This feature and a variant are further described below with reference to Figures 21 and 22.

In assembling and testing the components of the apparatus described hereinabove and illustrated in the drawings, the following procedure is recommended: Each blood unit 28 is tested separately and each water unit 26 is tested separately before assembling. Each blood unit is tested by clamping it in a testing device comprising plates similar to the end plates I la and I Ih, filling it with distilled water, and observing whether water leaks, either by observation of pressure change or by observation of drop in a column of water in a transparent tube extending up from the outlet.

The water unit may be tested similarly but more conveniently by filling it with air under pressure and observing a pressure gauge to determine holding or loss of pressure.

Then the blood and water units are assembled including spacers as shown at 50 and 65 in Figures 8, oxygen screens as shown in Figure 8, and inserts as shown at 47 in Figure 5, end plates I la and 1 lb as shown in Figure 6 and bolts 13 are applied and their nuts are tightened. A room temperature vulcanizing adhesive is applied to the spaces 100 between the spacers 50 and the stack of water and oxygen units 26 and 27. There are four such spaces, one at each corner, two such spaces being shown at 100 in Figure 3, the cured or vulcanized adhesive being shown at 101.

Then the assembly of blood, oxygen and water circuits is tested as follows: The water circuit is filled with compressed air and a pressure gauge is employed to determine whether there is a drop in pressure. Then the blood circuit is tested by filling it with distilled water while maintaining air pressure in the water circuit. Any outward leakage from the blood circuit is visibly evident. A leak from the interior of the blood circuit, e.g., from one of the blood envelopes, is made evident by the presence of water in the oxygen circuit which remains open and will leak water through its outlet.

All parts of the oxygenator to be in contact with any of the circulating fluids (blood, water and oxygen) are sterilized, for example, by known ethylene oxide sterilization procedures.

In use, the assembled apparatus is connected as shown in Figure 1 and as described above, to water and oxygen supplies and to the venous and arterial systems of the patient and to other necessary equipment.

In the description above and in Figures 3, 5 and 13 the semi-permeable membranes 33 are shown as being heat sealed at 46 to the side members 31 of blood frame 30. Difficulty may be encountered at the junctions of the heat seals along the side members 31 and the end members 32, such as wrinkles in the membrane in the adjacent area. This may be remedied by relying upon pressure seals along the side members rather than heat seals. leaving heat seals only along the end members 32. The chamfers 94 (see Figure 7) and the advantages conferred by them as described above allow such pressure seals to be used if such are deemed advisable.

Dimensions of the apparatus are of importance in the light of requirements of a patient. Following criteria and recommendations will be of help in the practice of the invention: The blood circulation of the average adult person at rest is about 5 litres of blood per minute, and the patient will require about 200 cc of oxygen per minute at atmospheric pressure and body temperature (98.6'F). It has been found that these requirements are met by apparatus having approximately twelve blood units each 7-1/2 inches from blood inlet to outlet side, and 18 inches in width of blood paths. More precisely, these dimensions are 7-1/2 inc scribed and illustrated above are the following: The components may be made of readily available and relatively inexpensive plastics material by economical methods, such as molding and/or stamping. The overall dimensions are typically about 23 inches in length, 10 inches in width, and 4 inches in height (a total volume of 920 cubic inches) which is a convenient size for use in an operating facility. (Length is the long dimension in Figure 1, width is the distance between the outer surfaces of the end plates apd height is the distance between the upper and lower edges of the end plates in Figure I.) The apparatus can be manufactured at a cost such that it is disposable and may be used once and discarded.

The water and blood circuits operate at pressures higher than the pressure in the oxygen circuit, and the water and blood circuits are so designed that any leakage from the water circuit will be either to the exterior of the apparatus or into the oxygen space. Therefore, leakage of water into the blood circuit is precluded.

The chamfer 94 described above with reference to Figure 7 ensures a tight, even application of pressure. Reference is now made to Figure 21 which also shows one of two gaskets 95 of compressible material such as rubber which are placed only on those long sides where there are no blood manifolds 17 in the end plates lla and llb. To prevent contact of rubber with blood, these gaskets are covered with a blood-compatible plastic polyethylene on the side facing the stack. As bolt pressure is applied the tapered edges of the cover plates bend about the fulcrum lines 94a where the plane of the chamfer 94 meets the plane of the flat major interior surfaces of the end plates. This causes the central portion of the end plates to bend outwardly. When the apparatus is in operation with water flowing through the water mattresses at, for example, 12 psi gauge pressure, the water pressure combined with the tension in the bolts causes additional outward bending of the central portion of the end plates. It will be understood that such a bending is very small in magnitude but is sufficient to reduce the pressure intensity along the inside seal line. If the elasticity of the compressed stack is low, leakage of blood into the oxygen space may result. This elasticity is ensured by the presence of the gaskets 95 to prevent leaks. The directions of the forces involved are shown in Figure 21 by the arrows.

Referring now to Figure 22, which is similar to Figure 7, the use of a tapered wedge 96 is shown which provides the chamfer 94. An advantage of this construction is that tapered wedges may be less expensive to manufacture than chamfered end plates. Another advantage is that if different chamfers are required for different materials or construction of the stack 12 and/or for different sizes of stacks, the end plates may be uniform but fitted with appropriate wedges.

Referring now to Figures 14 and 20, an alternative form of water unit is there shown and is designated generally by the reference numeral 26a. It comprises a water mattress 110 formed of water-impermeable, gas-impermeable, flexible material as in the case of the mattress 52 shown in Figure 8 and described hereinabove. This mattress is fitted at one end (the right-hand end as viewed in Figure 14) with two inserts 111, each formed with a water flow-through slot 112 and with lateral passages 113. At its other end the bladder is fitted with an oxygen insert 114, which is of solid construction and is formed with two oxygen flow-through slots 115. Aside members (not shown) such as those shown at 50 in Figure 8 will be employed.

The construction of the water insert 111 may be as shown in Figure 8, that is to say, it may be formed of three pieces, or it may have, and preferably it does have, the simpler two-piece construction shown in Figure 9.

The water mattress 110 is sealed at 116 from one end (the right end or water end) to a point short of the oxygen insert, thereby leaving a space 117.

In operation with this type of water unit, oxygen flows through the slots 115 in the oxygen insert 114 without access to the interior of the water mattress. Meanwhile water flows in through the slot 112 in one of the inserts 111 and a portion of the water flows through the lateral passages 113 into the interior of the water mattress on one side of the seal 116, then through the space 117 to the other side and out through the lateral passages 113 and slot 112.

An advantage of this type of construction is that it minimizes the extent of stagnant areas of water.

Referring now to Figures 15 to 19, an alternative form of oxygen unit is there shown which is generally designated by the reference numeral 120. It comprises a screen 121 which, except in the respects mentioned immediately below, is identical with the screen 68 shown in Figure 8. The screen 120 is slotted at 122 and is punched with holes 123.

At one end the screen 121 butts against a water flow-through insert 124 having slots 124A which register with the slots 112 of the water units. At its other end the oxygen unit is provided with an oxygen insert 125 which is formed with oxygen flow-through slots 126 and lateral passages 127. As will be seen in Figure 17, the inner edge of the insert 125 is bifurcated to receive the adjacent end of the screen 121. Further, the oxygen insert 125 is of two-piece construction as shown in Figure 18, and the bottom piece is provided with pegs 128 which extend through holes 123 in the screen 121 and into holes 130 in the top piece.

As will be further seen, a T-member 135 is provided the leg of which fits into the slot 122 in the screen 121 and is also received in a notch 136 in the insert 125 to lock the screen 121 and the insert 125 together. This oxygen unit will be provided with side pieces 50 as shown in Figure 8.

In operation water flows through the passages 124A without access to the interior of the oxygen unit and oxygen flows through one of the slots 126 and a portion of the oxygen flows through the lateral passages 127 into the interior of the oxygen unit on one side of the T, then around through the space 137 at the end of the T and through the passages 127 into the other slot 126 and thence to the next level.

The blood oxygenator described above employs a gas-permeable, water-impermeable member through which only gases flow.

However, the apparatus of the invention is applicable to a more recent type of oxygenator which employs an aqueous solution of hydrogen peroxide as the source of the oxygen gas. This type of oxygenator employs a semi-permeable membrane through which water as well as gas may flow and through which small solute molecules such as inorganic salts may also pass. The membrane is provided with a catalyst that acts to break down the hydrogen peroxide diffusing through it into water and oxygen. The hydrogen peroxide solution also contains salts to maintain a suitable osmotic pressure, such salts being compatible with the blood of the patient. This type of oxygenator is described in U. S. Patents Nos. 3,846,236 and 3,996,141 and in papers by the patentee, Stuart Updike, in Transactions of the American Society of Artificial Internal Organs, Vol. 19, page 529, and Vol. 20, page 286.

In applying the present invention to this type of oxygenator, the only changes (other than size, which could be smaller with the hydrogen peroxide system) would be to use an appropriate semi-permeable membrane which is permeable to gas, water and small solute molecules but impermeable to the formed elements of the blood such as red and white blood cells, platelets etc., and to proteins carried by the blood, etc. The membrane would also embody a catalyst.

Further, the oxygen circuit and its components would be used with aqueous hydrogen peroxide solution rather than gaseous oxygen.

The embodiment of Figures 23 to 32 will now be described.

Referring now to the drawings and preliminarily to Figures 23, 24 and 25, the device is indicated generally by the reference numeral 210 and it comprises a container 211 having a top 212, two sides 213 (one of which is shown in Figure 24), two end walls 214 and a bottom 215. Bolts 216 and nuts 216a (see Figures 27 and 28) serve to bolt the side and end walls to the bottom. Bolts 217 and nuts 217a bolt the top 212 to the bottom 215 and serve also to clamp the blood, water and oxygen units together and to resist water pressure and to maintain uniformity of the blood paths. As shown in Figures 27, 28 and 29, O-rings 218 are provided in grooves 21 8a as seals between the side and end walls 213 and 214 and the bottom 215. The cover 212 is provided with tongues 220 which fit into grooves 221 in the side and end walls, the spaces between the tongues and grooves being filled with a waterproof cold setting glue 222. A blood inlet is shown at 225, an oxygen outlet at 226 and a water inlet at 227.

A blood outlet is shown at 225 a, an oxygen inlet at 226a and a water outlet at 227a. (See Figures 23 and 24.) Referring again to Figures 27, 28 and 29, a typical assembly is shown including (from top to bottom) a water unit 230, an oxygen unit 231 and a blood unit 232, a second oxygen unit 231, a second water unit 230, etc.

As will be seen, each blood unit 232 is sandwiched between two oxygen units 231 and in every instance a blood unit 232 is separated from the adjacent water unit or units 230 by an oxygen unit or units 231. The order or sequence of units 230, 231 and 232 is elaborated below.

Referring now to Figure 25, the topmost blood unit 232 shown in that figure is illustrated in exploded view. It includes two membranes 233 which form a blood space 233a between them (see the blood unit below that shown in exploded view), a screen 234 located in the blood space 233a between the top and bottom membranes 233, side frame members 235 and end frame members 236, one at each end of the unit. Each side member 235 is made in two parts consisting of a lower part 237 and an upper part 238.

The lower part 237 is formed with parallel transverse grooves 239 which provide channels for the flow of blood (inflow on the entry side of the blood unit and outflow on the exit side of the blood unit). Spaced at intervals along each side member 235 are bolt holes 240 to receive bolts 217. Elsewhere, as will appear, there are other bolt holes 240 which together with bolts 217 and nuts 21 7a serve to secure the cover on the box, to hold the assembly of blood, water and oxygen units together, and to resist the pressure of the water units in a manner and for a purpose which is explained below. At each end each of the side members 235 is formed with a notch 245 and with a chamfered end portion 246 to mate with a similarly chamfered portion 247 of the adjacent end piece 236. At each end. each end piece 236 is also formed with a notch 248. The notches 245 and 248 (also similar notches in other elements of the apparatus as shown in the drawings) are intended to receive tongues 249 projecting in from the side and end walls of the housing so as to key together the inner components of the apparatus and to align them properly.

See Figure 26.

Referring again to Figure 25, water units 230 are there shown, each comprising an envelope 260 sealed along its long sides or molded in the form of a seamless sleeve. At each end of the envelope there is an insert 261 made in two pieces consisting of a lower piece 262 and an upper piece 263, both of which are slotted at 264, the lower part being also formed with transverse grooves 265. The envelope 260 is sealed at its end at 268 and it is formed with slots 269 in registry with slots 264. Also, the envelope 260 is formed with bolt holes 240 in registry with bolt holes 240 in inserts 261. The pattern of these bolt holes is shown in Figure 26 and is discussed below.

Referring now to Figures 25, 27 and 28, each oxygen unit 231 is formed by a screen 275 located between the membranes 233 of the neighbouring blood units 232 (or by an adjacent membrane 233 of a blood unit and the wall of a bladder 260 as at the top and bottom of the assembly as shown in Figures 27, 28 and 29 and by side frame pieces 276.

The side pieces 276 are of a thickness equal to the combined thickness of two oxygen units 232 and ohe water unit 230 except at the top and bottom of the stack where they are of a thickness equal to the combined thickness of a single oxygen unit 231 and a single water unit 230. See Figure 28.

Spacers 277 are provided at the ends of the assembly between neighboring water units 230. These spacers 277 are coextensive with the inserts 262 in the water units and therefore leave open the ends of the oxygen units beyond these spacers. See Figures 25 and 29. This provides oxygen plenums as and for a purpose described below. The spacers 277 are slotted at 278 in registry with the slots 269 in the water envelopes and the slots 264 in inserts 26 1.

The inserts 261 of each water unit 230 are preferably diagonally situated as are the open ends of the oxygen units, whereby the flow of water through each water unit is from one corner to the diagonally opposite corner and the flow of oxygen through each oxygen unit is from one corner to the diagonally opposite corner.

Blood passes through the assembled device from the blood inlet 225 to a plenum 285 (see Figure 28) and at the level of each blood unit 232 a portion of the blood flows through the grooves 239 into the blood space 233a between the membranes 233, thence across the blood space to the opposite side member 235 and through its grooves 239 to a blood plenum 285, thence out through the blood outlet 225a to the arterial system of the patient.

Water flows in through the water inlet 227 then through the slots 269 in the water envelopes 260, through the slots 264 in the inserts 261 and through the slots 278 in the spacers 277. At each level a portion of the water flows through the grooves 265 into the respective envelope at one end and diagonally across the envelope out through grooves in the other end piece. See Figures 25 and 27 (As described above with reference to Figures 1-22, diagonal flow is preferred because it minimizes channeling and uneven flow.) The water in the water units 230 performs not only the function of applying pressure but also of controlling blood temperature. The water units therefore function as internal, integral heat exchangers and dispense with the need of a heat exchanger external to the oxygenator.

Referring now to Figures 26 and 29, an oxygen plenum 290 is provided at each end of the assembly, one such plenum being shown in Figures 26 and 27 (the oxygen inlet end), there being a similar plenum (not shown) at the other end which is preferably diagonally situated with respect to the inlet plenum. At the level of each oxygen unit 231 a portion of the oxygen flows into the respective oxygen unit (as indicated by the arrows in Figure 29 thence through the unit to the plenum at the other end and out through oxygen outlet 226.

Referring to Figure 26, as noted above the side and end walls of the housing are formed with tongues 249 to fit into the corresponding notches 245 of the various side and end members. This construction serves to align the elements of the assembly properly and it leaves cavities 295 to receive a cold setting glue 296 which is introduced after the units 230, 231 and 232 are assembled in the housing and before the cover 212 is applied.

The glue serves to seal the assembly and to prevent shunts or leaks. That is to say, leakage of oxygen and of the fluids around corners is prevented.

The apparatus illustrated in Figures 23 and 32 is, of course, used in conjunction with auxiliary equipment such as that described in connection with Figures 1 to 22 and the same order of water (W), oxygen (0) and blood (B) units are preferably employed.

Also, materials of construction may be as described in connection with Figures 1 to 22.

Similar procedures may be employed in testing the components of the apparatus of Figures 23 to 32 but for the sake of completeness and because there are differences these procedures are described below.

Each blood unit 232 is tested separately for leaks and each water unit 231 is tested separately for leaks before assembling. Each blood unit is tested by clamping it between plates in a testing device, filling it with distilled water, and observing whether there are water leaks, either by observation of pressure change or by observation of drop in a column of water in a transparent tube extending up from the outlet.

The water units 230 may be tested similarly but more conveniently by filling them with air under pressure and observing a pressure gauge to determine holding or loss of pressure.

When the units have been assembled the water circuit is filled with compressed air and a pressure gauge is employed to determine whether there is a drop in pressure. Then the blood circuit is tested by filling it with distilled water while maintaining air pressure in the water circuit. Any outward leakage from the blood circuit is visibly evident. A leak from the interior of the blood circuit, e.g., from one of the blood envelopes, is made evident by the presence of water in the oxygen circuit which remains open and will leak water through its outlet.

After assembly the oxygenator is sterilized, for example, by approved ethylene oxide sterilization procedures.

Assembly is carried out as follows: The housing 11 is constructed except for the cover 212, by applying O-ring seals 21 8a to grooves 218 and applying bolts 216 and nuts 216a to erect the side and end walls 213 and 214 on the bottom or base 215. Referring now to Figures 25, 27, 28 and 29, the bolts 217 (without nuts 217a) are installed. Then the first side pieces 276 are installed by threading them over bolts 217 along the sides of the housing. Then the first (bottommost) water unit 230 is installed by threading the bolts 217 through the bolt holes 240 in the inserts 261 and water bladder 260. The end spacers 276 are then installed. Then an oxygen screen 275 is laid over the water bladder within an area defined by the side pieces 276 and end spacers 277. Then a blood unit 232 is installed by threading the bolts 217 through the bolt holes 240 in the side pieces 235 and the membranes 233 of the blood unit. This procedure is then repeated until the full complement of blood, water and oxygen units and the necessary side pieces 276 and end spacers 277 have been installed, care being taken to select side pieces 276 of proper thickness to bridge the space between successive modules. Also, account is taken of the order of W, 0 and B units. The top and bottom units are water units. The cover 212 is applied by fitting the circumferential tongues 220 into the grooves 221, passing the bolts 217 through the bolt holes 240 in the cover and applying and tightening the nuts 217a.

Adhesive is applied through injection ports (not shown) in the cover to the circumferential grooves 211 in the side and end walls 213 and 214.

In start up and after testing the apparatus is primed and in priming care is taken to remove all air or other gas from the blood and water circuits. This is aided by tilting the housing 211 so that the long edge of the housing (i.e., the edge viewed in Figure 24) is lower than the opposite edge and so that the blood inlet, right-hand end of the housing (as viewed in Figure 24) is lower than the lefthand end. Therefore, the blood flow (also the water flow) at all times has an upward component. Therefore, when the apparatus is primed and ready for use, it is free of entrapped gas, and it remains free of gas during use. This is, as noted, especially important in the case of the blood circuit.

The apparatus is held, by suspension or otherwise, in this doubly tilted attitude (i.e., tilted about one edge and about one end) during use.

Referring to Figure 26, it will be seen that the water outlet 227a which is shown in broken line (also the water inlet 227 diagonally opposite and at the other end of the housing) are centered on the slots 264 and that the bolts 217 are symmetrical with respect to the slots 264 (although the inside bolts 217 are spread farther apart to avoid interference with the grooves 265, see Figure 25). This provides (when the nuts 217a are tightened) a more secure and uniform seal between the spacers 277 and the water envelope 260. Also, joints between the top and bottom envelopes 260 and the water inlets and outlets 227 and 227a are made more secure and leakproof.

The cover 212 serves to react against or resist the water pressure in the water units 230. The water pressure is controlled to exceed that of the blood pressure in the blood units 232. If the water envelopes 260 were allowed to expand freely, unequal pressures would be applied to the membranes 233. The cover 212 acts to prevent this, to apply pressure evenly to the membranes 233 and to hold them against the screens 234 (which define the depth of the blood paths) so as to ensure uniformity of depth of the blood paths.

As in the case of the apparatus of Figures 1 to 22, dimensions of the apparatus are of importance in the light of requirements of a patient. The same or similar criteria and recommendations apply to the apparatus of Figures 23 to 32.

As in the case of Figures 1 to 22 the water and blood circuits operate at pressures higher than the pressure in the oxygen circuit, and the water and blood circuits are so designed that any leakage from the water circuit will be either to the exterior of the apparatus or into the oxygen space. Therefore, leakage of water into the blood circuit is precluded.

Also, as in Figures 1 to 22 gas permeablewater impermeable membranes may be used or, in the event that hydrogen peroxide is used, membranes permeable to water and small solute molecules but impermeable to larger constituents of the blood may be used.

Among advantages of the apparatus of Figures 23 to 32 (in addition to advantages shared with the apparatus of Figures 1 to 22) are the following: The blood plenums 285 (see Figures 23, 26 and 28) ensure a more uniform flow of blood through the blood paths 233a. Note that they are oppositely tapered, being widest at the blood entry end in the case of the plenum on one side (the blood entry side) and narrower at the other end while on the opposite (blood outlet) side the taper is opposite to adjust for the diminishing flow of blood on the entry side from the blood inlet to the opposite end and for the increasing volume of blood in the same direction on the outlet side. Blood does not flow vertically (as viewed in Figure 28) through the side members 235 of the blood frame, but only horizontally through the grooves 239. This simplifies construction and it avoids stagnant regions in the blood supply.

The oxygen plenums 290 (see Figures 26 and 29) provide similar advantages.

From Figure 28 it will be seen that the bolts 217 are on the centre lines of the pieces 276. Likewise, as explained above and as shown best in Figure 26, the bolts 217 passing through the inserts 261 and through the spacers 277, although not on centre lines, are symmetrical to the centre lines of these members. The pressure exerted on the assembly of the members 235, 260, 276 and 277 therefore acts uniformly and applies a uniform sealing pressure to the blood and oxygen units and prevents leakage of any of the fluid into the wrong units.

In the apparatus shown in Figures 23 to 32 and described above, the water circuit is at a higher pressure (e.g. at 14 psig) than the blood (e.g. 6 psig). Therefore the water envelopes 260 will tend to expand. The expansive force of the water envelopes 260 is resisted by the cover 212 and the bottom 215 whereby the depths of the blood paths 233a are kept uniform. It is an advantage of the structure shown that the cover may be of relatively thin, flexible material, e.g. 1/16" to 1/8" polypropylene.

Yet another advantage is that it permits the use of a box-like housing 211 which, together with the assembly of units 230, 231 and 232 and side pieces 276 and the end spacers 277 form inlet and outlet blood and oxygen plenums. This considerably simplifies construction, e.g., it avoids the need to provide blood and oxygen flow through passages (i.e. for flow from one blood or oxygen unit to the next) in frame members used to construct the blood and oxygen units.

An alternative type of water unit 300 is shown in Figures 332. The unit 300 has a frame 301, made in two parts which are sealed together and having end portions 302 (only one being shown in Figure 30), side portions 303 and at each end a widened portion 304 which serves, in the manner described below, as a water distributor and flow-through member. This frame is made of two identical parts, an upper part (as viewed in Figures 31 and 32) 305 and a lower part 305a which are sealed together at 306 by any suitable means. Polyethylene or other suitable flexible, expansible water-impervious sheets 307 are sealed, e.g. by heat, to the top and bottom halves of the frame to form a water spacer 307.

The member 304, which corresponds to the insert 261 in the other Figures previously described is formed with slots 308 and grooves 309. The sheets 307 are formed with slots 310 in registry with the slots 308. The slots 308 and 310 are in registry with the slots 278 and the spacers 277 (see Figure 27) for flow of water from one water unit 300 to the next, and at the level of each water unit a portion of the water will flow through the grooves 309 into the water space 311, across the water space and out through an identical distributor member 304 (not shown) at the other end and preferably diagonal to the distributor shown in Figure 30.

WHAT I CLAIM IS: 1. A blood oxygenator of the membrane type, which includes a set of blood, water and oxygen units disposed in stacked relationship and comprising at least one blood unit sandwiched between and adjacent to oxygen units, each said blood unit comprising a semi-permeable blood envelope equipped at each end with a plurality of blood flowthrough passages for the main flow of blood through the stack and for diverting a portion of such main flow of blood into the interior of the blood envelope for flow through said interior, each said water unit comprising a flexible water impermeable water envelope equipped at each end with a plurality of water flow-through passages for the main flow of water through the stack and for diverting a portion of such main flow of water into the water envelope for flow of water therethrough, the blood flow-through passages of the blood envelopes lying outside the perimeter of the water envelopes and the water flow-through passages of the water envelopes lying outside the perimeter of the blood envelopes, each oxygen unit occupying the space between a blood unit and a water unit or between two blood units and having an inlet and an outlet for flow of oxygen or hydrogen peroxide solution into, through

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. water into the blood circuit is precluded. Also, as in Figures 1 to 22 gas permeablewater impermeable membranes may be used or, in the event that hydrogen peroxide is used, membranes permeable to water and small solute molecules but impermeable to larger constituents of the blood may be used. Among advantages of the apparatus of Figures 23 to 32 (in addition to advantages shared with the apparatus of Figures 1 to 22) are the following: The blood plenums 285 (see Figures 23, 26 and 28) ensure a more uniform flow of blood through the blood paths 233a. Note that they are oppositely tapered, being widest at the blood entry end in the case of the plenum on one side (the blood entry side) and narrower at the other end while on the opposite (blood outlet) side the taper is opposite to adjust for the diminishing flow of blood on the entry side from the blood inlet to the opposite end and for the increasing volume of blood in the same direction on the outlet side. Blood does not flow vertically (as viewed in Figure 28) through the side members 235 of the blood frame, but only horizontally through the grooves 239. This simplifies construction and it avoids stagnant regions in the blood supply. The oxygen plenums 290 (see Figures 26 and 29) provide similar advantages. From Figure 28 it will be seen that the bolts 217 are on the centre lines of the pieces 276. Likewise, as explained above and as shown best in Figure 26, the bolts 217 passing through the inserts 261 and through the spacers 277, although not on centre lines, are symmetrical to the centre lines of these members. The pressure exerted on the assembly of the members 235, 260, 276 and 277 therefore acts uniformly and applies a uniform sealing pressure to the blood and oxygen units and prevents leakage of any of the fluid into the wrong units. In the apparatus shown in Figures 23 to 32 and described above, the water circuit is at a higher pressure (e.g. at 14 psig) than the blood (e.g. 6 psig). Therefore the water envelopes 260 will tend to expand. The expansive force of the water envelopes 260 is resisted by the cover 212 and the bottom 215 whereby the depths of the blood paths 233a are kept uniform. It is an advantage of the structure shown that the cover may be of relatively thin, flexible material, e.g. 1/16" to

1/8" polypropylene.

and out of the oxygen unit, and the water and blood units being configured so as to form pathways extending through the stack, said pathways isolating the water flowthrough passages from the blood flowthrough passages so that if water leaks from a water flow-through passage such leakage will be routed by said pathways to an oxygen unit or to the exterior of the stack or to both rather than to a blood flow-through passage.

2. A blood oxygenator according to claim I, in which the blood unit is constituted by a flat frame, the side and end dimensions of which are larger than the thickness thereof and the active interfaces of which are formed by the semi-permeable envelope, which provides, in the interior thereof, a blood circulation path in communication with a plurality of blood inlet ports and a plurality of blood outlet ports located at opposite sides of the frame, the blood inlet ports and the blood outlet ports being in flow communication with the blood flow-through passages.

3. A blood oxygenator according to claim 2, in which the blood unit is constituted by a generally rectangular structure.

4. A blood oxygenator according to claim 1, in which each water unit is constituted by a flat frame, the side and end dimensions of which are larger than the thickness thereof and the interior of which is formed by the flexible water-impermeable water envelope, said frame being provided with water inlet ports and water outlet ports in communication with the interior of said water envelope and with water flow-through ports to communicate with other water units in the oxygenator.

5. A blood oxygenator according to claim 1, in which each water unit is provided with inserts at each end and within the water envelope, at least one of said ends being formed with said water flow-through passages and with flow-through ports for flow of water into, through and out of said water envelope.

6. A blood oxygenator according to claim 1, in which each water unit is provided with an insert at one end of the water envelope having two water flow-through ports and a lateral passage for communicating with the interior of the envelope, and an oxygen insert at the other end of the water envelope having an oxygen flow-through port isolated from the interior of the water envelope which contains a longitudinal barrier to establish a circuitous flow of water through the envelope from one water flowthrough port to the other.

7. A blood oxygenator according to claim 1, which includes a stack of sets, each set including blood, oxygen and water circulation units, said stack being provided, at the periphery thereof with passages for flow of blood, water and oxygen through the stack and with inwardly extending passages in communication with said blood, water and oxygen units, the passages constituting conduits for the separate flow of each fluid through the stack from one end to the other end, and also constituting conduits for the flow of each fluid at different levels of the stack into and through the respective blood, water and oxygen units.

8. A blood oxygenator according to claim 1, wherein the blood envelope includes a screen which acts to distribute the blood evenly to promote diffusion of oxygen into the blood and to define the thickness of the blood path in the envelope.

9. A blood oxygenator according to claim I, which includes a plurality of blood units each of which comprises a rectangular frame having imperforate ends, the inlet side of the frame being formed with flow-through passages for flow of blood from one blood unit to the next, the outlet side of the frame being also formed with flow-through passages for flow of blood from one blood unit to the next, said sides being also formed with lateral flow passages for flow of a portion of the blood stream flowing through the apparatus into, through and out of the respective blood envelope and the flow-through passages in both sides of the blood frames being in registry with one another to allow flow of blood from one blood unit to the next.

10. A blood oxygenator according to claim 1, in which the stack is provided, at each end thereof, with an end plate having a contact surface provided with an interior flat major portion constituting a closure for the stack, each end plate being provided, close to the periphery thereof, with flow-through passages in communication with the flowthrough passages of the stack, one end plate corresponding to the inlet ports of the fluids flowing through the stack and the other end plate corresponding to the outlet ports of the stack and each end plate being provided, on the periphery of the contact surface thereof, with a chamfer forming a small angle with its flat portion, the plane of said chamfer intersecting the plane of the flat portion inwardly of the flow-through passages of the plates and stack, said oxygenator including clamping means located outwardly of the flow-through passages substantially in the area of the chamfers to provide a tight, leakproof seal between the plates and the adjacent units and between the units.

11. A blood oxygenator according to claim 10, wherein the chamfers are formed on the end plates.

12. A blood oxygenator according to claim 10, wherein the chamfers are formed by separate wedges.

13. A blood oxygenator according to claim 10, which includes compressible gaskets interposed between the chamfers and the stack.

14. A blood oxygenator according to claim 4, wherein the sides of the water frame are spaced from the ends of the water frame and from the sides of the water envelope to form gaps which form a portion of the isolating pathways.

15. A blood oxygenator according to claim 1, wherein the isolating pathways are so configured to form open gaps serving to route any leakage of water from a water flow-through passage to the exterior of the stack or to an oxygen unit or to both.

16. A blood oxygenator according to claim 1, wherein the isolating pathways provide open gaps between structures having water flow-through passages and structures having blood flow-through passages, such gaps serving to route any leakage of water from a water flow-through passage to the exterior of the stack or to an oxygen unit or to both.

17. A blood oxygenator according to claim 1, which includes side spacers spanning spaces between successive blood units and end spacers spanning the spaces between successive oxygen units, the side spacers being formed with blood flow-through passages in registry with the blood flow-through passages of the blood units and the end spacers being formed with water flowthrough passages in registry with the water flow-through passages of the water units.

18. A blood oxygenator according to claim 1, which includes a housing enclosing the stack of units and providing inlet and outlet plenums for the blood units, or for the oxygen units or for both the blood and oxygen units whereby the respective fluid or fluids flow into the respective units from an inlet plenum space on one side of the stack and out of the respective units into an outlet plenum space on the opposite side of the stack.

19. A blood oxygenator according to claim 18, which includes both oxygen plenums and blood plenums.

20. A blood oxygenator according to claim 19, wherein the units are rectangular in shape, the housing is a box-like housing having a bottom, side walls, end walls and a cover, the blood plenums ae formed by the bottom, cover and side walls of the housing and by the stack and the oxygen plenums are formed by the bottom, cover and end walls of the housing and by the stack.

21. A blood oxygenator according to claim 18, which includes a cover, and means securing the cover to the side and end walls of the housing whereby the cover acts to resist the expanding force of water in the water units and thereby maintains predetermined thickness of the blood paths provided by the blood units between the inlets and outlets thereof.

22. A blood oxygenator according to claim 21, wherein the side and end walls are secured together by members passing through them.

23. A blood oxygenator according to claim 21, wherein the oxygen units are provided with inlets and outlets for flow of oxygen through the units from end-to-end between an oxygen inlet plenum and an oxygen outlet plenum each bounded by the assembly of units and an end wall, the cover and the bottom of the housing.

24. A blood oxygenator according to claim 21, wherein the inlets of the oxygen units are in flow communication with an oxygen plenum formed by one- end wall, the cover and the bottom of the housing and the assembly of units and the outlets of said oxygen units are in flow communication with an oxygen plenum formed by the other end wall, the cover and the bottom of the housing and the assembly of units, the inlets of said blood units are in flow communication with a blood inlet plenum formed by one side wall, the cover and the bottom of the housing and the assembly of units and the outlets of the blood units are in flow communication with a blood outlet plenum formed by the other side wall, the cover and bottom of the housing and the assembly of units.

25. A blood oxygenator according to claim 1, substantially as hereinbefore described with reference to Figures 1 to 8, 10 to 13 and 21 or to Figures 1 to 8, 10 to 13 and 21 as modified by Figures 9, 14 to 20 and 22 or to Figures 23 to 29 or to Figures 23 to 29 as modified by Figures 30 to 32 of the accompanying drawings.