Abstract:
A low prime membrane oxygenator and an integrated heat exchanger/reservoir for use alone or in combination in an extracorporeal blood circuit. The oxygenator has a simple, five-part construction including a housing defining an annular oxygenation chamber within which a plurality of hollow fibers are arranged in an annular bundle with flow spaces therebetween. A blood inlet port and manifold deliver blood through a plurality of evenly circumferentially spaced inlet apertures to the oxygenation chamber, and blood flows generally axially through the elongated annular chamber to a plurality of evenly circumferentially spaced outlet apertures. A gas inlet communicates with a header space to deliver gas having a high oxygen content to internal lumens of the fibers. Gas transfer between the blood and gas takes place through the semi-permeable hollow fiber membranes in the oxygenation chamber. Specific geometric ratios, a particular hollow fiber architecture, and the absence of a heat exchange function, all combine to reduce the prime volume required by the oxygenator. The reservoir includes a hard outer shell topped by a lid with a venous blood inlet. Blood from the inlet enters an elongated annular heat exchange chamber defined between two vertical cylindrical walls within the reservoir. A plurality of heat exchange coils in the annular chamber provides an efficient heat transfer function with low prime volume requirement. Cardiotomy fluid may be first debubbled and then combined with the venous blood stream entering the heat exchange chamber. After passing through the heat exchange chamber, the blood passes through a series of filters before being pumped to the oxygenator.

Description:
RELATED APPLICATION  
       [0001]    The present application is a divisional of application Ser. No. 09/075,409, filed May 8, 1998. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates generally to extracorporeal fluid circuits and, more particularly, to a compact membrane oxygenator and combined reservoir/heat exchanger used alone or in conjunction to reduce the prime volume of an extracorporeal blood circuit.  
         BACKGROUND OF THE INVENTION  
         [0003]    Cardiopulmonary bypass (CPB) surgery requires a perfusion system, or extracorporeal oxygenation circuit, to maintain an adequate supply of oxygen in the patient&#39;s blood during the surgery. A venous return cannula inserted in one of the veins leading directly to the heart receives the “used” blood for rejuvenation through the perfusion system. The blood flows out of the patient into an extracorporeal fluid circuit having a conduit (typically a transparent flexible tube) to a venous reservoir that may also receive fluid from cardiotomy suckers. Commonly, one or more suckers extracts excess fluid from the chest cavity during the operation and diverts the fluid, which may contain bone chips or other particulates, into the top of the reservoir.  
           [0004]    Typically, a centrifugal or roller pump impels blood, for example, from the venous/cardiotomy reservoir through a blood oxygenator and back to the patient. The pump assumes the pumping task of the heart and perfuses the patient&#39;s circulatory system. The oxygenator directs a flow of blood across a semi-permeable membrane or a plurality of semi-permeable fibers to transfer oxygen to and carbon dioxide from the blood. The oxygenator often incorporates a heat exchange system to regulate the extracorporeal blood temperature, termed a “closed” system. Before reaching the patient, the blood may pass through a temperature control monitoring system and along a conduit through an arterial filter and bubble detector, before reaching an arterial cannula positioned in a main artery of the patient.  
           [0005]    The various components such as the reservoir, oxygenator and arterial filter require a minimum volume of blood to begin circulation. All of the components taken together require a “prime” volume of blood defined as that volume of blood outside the patient, or extracorporeal. The term “prime volume” can also be used to specify the volumetric capacity of each extracorporeal component in the system.  
           [0006]    There are number of performance measurements for oxygenators. Important considerations include gas transfer capabilities, priming volume, blood compatibility, sterility, assembly, and maintenance. Effective oxygenators provided sufficient gas transfer with a minimum pressure drop and prime volume. In addition, the flow capacity through the oxygenator must be sufficient for the particular patient. Often, there is a trade-off in one or more of these performance characteristics to obtain a low priming volume or high flow rate, for example.  
           [0007]    The need for a large prime volume in an extracorporeal fluid circuit is contrary to the best interest of the patient who is undergoing the surgery and is in need of the maximum possible amount of fully oxygenated blood. This is especially true of smaller adults, children, and pediatric or infant patients. Therefore, a significant amount of research and development has been directed toward reducing the prime volume within CPB systems. One area in which such a reduction of volume can be attained is to reduce the volume of the individual components, such as the reservoir, or blood oxygenator. There are limits to how small these components can be made, however, such as a need for adequate oxygen transfer to the blood, which depends in part on a sufficient blood/membrane interface area.  
           [0008]    Much of the development in recent years has been toward reducing the prime volume of oxygenators while maintaining adequate flow rate and gas transfer capabilities. Unfortunately, this is not an easily attainable goal, and many of the smallest prime volume oxygenators have such a reduced flow rate that they are only useful for neonatal or infant patients, or exhibit some other performance disadvantage. Conversely, many oxygenators which otherwise have adequate performance, require a higher priming volume. For example, most of the most widely used commercial membrane oxygenators on the market for adult patients have priming volumes of between 0.3 and 0.6 liters. Given the limited supply of the patient&#39;s blood, any decrease in priming volume in the oxygenator or other components of the extracorporeal circuit greatly enhances the chances for a positive surgery and rapid recovery.  
           [0009]    In spite of ongoing advances in extracorporeal circuit technology, there exists an ever-present need for a reduced prime CPB system.  
         SUMMARY OF THE INVENTION  
         [0010]    The present invention provides an improved low prime extracorporeal system including a low prime oxygenator and a low prime combined heat exchanger/reservoir. The dimensions of the oxygenator are optimized so that, in conjunction with a particularly preferred hollow fiber architecture, a prime reduction from currently available models as well as top performance results. Two sizes of oxygenator are disclosed which have the capacity to fulfill the needs of all ranges of patient weights, from the smallest neonatal baby to large adults. The oxygenators share certain preferred dimensions and elements, and essentially just differ in height. The combined heat exchanger/reservoir makes use of a single-pass guided heat exchanger configuration that decouples the heat exchange efficiency from the reservoir blood level.  
           [0011]    In one embodiment, the low prime oxygenator, comprises a rigid housing defining an annular oxygenation chamber having a first axial end and a second axial end. A plurality of elongated, hollow, semi-permeable fibers are arranged in an annular bundle in the oxygenation chamber and secured at both axial ends with a potting compound. The bundle substantially fills the oxygenation chamber with the fibers arranged to provide blood flow spaces therebetween, and the opposed ends of the fibers are open to a gas header space formed in the housing outside of the oxygenation chamber. A central blood inlet port is provided in communication with a blood distribution space adjacent one axial end of the oxygenation chamber. A plurality of blood inlets in the housing are formed around the annular oxygenation chamber in communication with the blood distribution space, while a plurality of blood outlets in the housing are formed around the annular oxygenation chamber on the axial end opposite the blood inlets. In an embodiment of the oxygenator suitable for adults, the oxygenator has a prime volume of between 130 and 180 ml and a ratio of oxygen transfer rate to prime volume of at least about 0.34 lpm/min, at a flow rate of about 7 lpm. In an embodiment of the oxygenator suitable for neonatal/infants, the oxygenator has a prime volume of between about 56 ml and 80 ml and an oxygen transfer rate of about 62.5 ml/min/lpm at a flow rate of about 2 lpm.  
           [0012]    The blood oxygenator of the present invention desirably has a simplified construction with a rigid housing consisting essentially of five parts, including: an inner core having a radial bottom wall and a cylindrical wall, an outer cylindrical wall concentric about the inner core cylindrical wall defining an annular oxygenation chamber therebetween having a first axial end and a second axial end, a pair of end caps connected to opposite ends of the outer cylindrical wall, and a blood inlet cap secured to the inner core. The inlet cap has a central blood inlet port in communication with a blood distribution space adjacent one axial end of the oxygenation chamber and formed between the inlet cap and the inner core bottom wall. A plurality of blood inlets in the inner core are formed around the blood distribution space in communication with the annular oxygenation chamber. The oxygenator includes a plurality of elongated, hollow, semi-permeable fibers arranged in an annular bundle in the oxygenation chamber and secured at both axial ends with a potting compound. The opposed ends of the fibers are open to a gas header space formed within the end caps outside of the oxygenation chamber. The bundle substantially fills the oxygenation chamber with the fibers having blood flow spaces therebetween. A plurality of blood outlets in the outer cylindrical wall are formed around the annular oxygenation chamber on the axial end opposite the blood inlets causing generally axial flow of blood through the oxygenation chamber and between the hollow fibers. The five parts of the oxygenator are either snap-fit together with O-ring seals, or are bonded with adhesive or UV welds.  
           [0013]    The present invention also embodies an extracorporeal system, comprising a combined heat exchanger/blood reservoir and a hollow fiber oxygenator. The reservoir has heat exchange elements located in a separate heat exchange chamber and a blood outlet. The oxygenator includes a blood inlet connected to the blood outlet of the heat exchanger/blood reservoir, and a rigid housing defining an annular oxygenation chamber having a cross-sectional area normal to its axis of between about 24 and 28 square centimeters. The oxygenation chamber has a first axial end and a second axial end, and the housing includes a central blood inlet port in communication with a blood distribution space adjacent one axial end of the oxygenation chamber. A plurality of blood inlets in the housing are formed around the annular oxygenation chamber in communication with the blood distribution space, while a plurality of blood outlets in the housing are formed around the annular oxygenation chamber on the axial end opposite the blood inlets. Finally, a plurality of elongated, hollow, semi-permeable fibers arranged in an annular bundle in the oxygenation chamber and secured at both axial ends with a potting compound. The opposed ends of the fibers are open to a gas header space formed in the housing outside of the oxygenation chamber. The fibers having an aggregate volume that is between 0.5 and 0.6 of the volume in the oxygenation chamber between the potting compound at both axial ends.  
           [0014]    A combined heat exchanger/blood reservoir, including a housing topped by a lid together defining a reservoir chamber within, a venous blood inlet in the lid, a heat exchanger within the chamber including a plurality of heat exchange elements, and a blood outlet in a lower portion of the reservoir chamber. The heat exchange chamber is defined by guides closely surrounding the heat exchange elements and extending downward from a location at an upper portion of the reservoir chamber. The heat exchange chamber has an upper inlet open to the venous blood inlet and a lower outlet open to the reservoir chamber so that blood from the venous blood inlet must flow through the heat exchange chamber before reaching the reservoir chamber. Preferably, the guides are concentric tubes defining an annular heat exchange chamber terminating at an elevation about ¼ of the distance from the bottom of the reservoir chamber.  
           [0015]    Further objects and advantages of the present invention shall become apparent to those skilled in the art upon reading and understanding the following detailed description of a presently preferred embodiment of the invention. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]    [0016]FIG. 1 is a schematic diagram of an extracorporeal circuit including elements of the present invention;  
         [0017]    [0017]FIG. 2 is a cross-sectional view of a heat exchanger/reservoir for use in adult extracorporeal circuits;  
         [0018]    [0018]FIG. 3 is a cross-sectional view of a low prime volume oxygenator for use in adult extracorporeal circuits;  
         [0019]    [0019]FIG. 3 a  is a sectional exploded view of the oxygenator of FIG. 3;  
         [0020]    [0020]FIG. 4 is a cross-sectional view of a heat exchanger/reservoir for use in neonatal/infant extracorporeal circuits;  
         [0021]    [0021]FIG. 5 is a cross-sectional view of a low prime volume oxygenator for use in neonatal/infant extracorporeal circuits;  
         [0022]    [0022]FIG. 5 a  is a sectional exploded view of the oxygenator of FIG. 5;  
         [0023]    [0023]FIG. 6 a  is a perspective schematic view of a step in the assembly of an exemplary hollow fiber bundle;  
         [0024]    [0024]FIG. 6 b  is a perspective schematic view of a step in the assembly of an another exemplary hollow fiber bundle; and  
         [0025]    [0025]FIG. 7 is a cross-sectional view of the adult low prime volume oxygenator of FIG. 3 showing various key dimensions. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0026]    [0026]FIG. 1 shows an example of a perfusion system  20  utilizing elements of the present invention including a venous line  22  leading from a patient into a venous input of a heat exchanger/reservoir  24 . The reservoir  24  may also include cardiotomy inputs, and the combined cardiotomy and venous fluid is filtered and heat treated before exiting through a lower outlet to a second conduit  26 . The conduit  26  leads to an input of a blood pump  28 , such as a centrifugal pump as shown, typically controlled by a controller (not shown). The outlet of the pump leads to a third conduit  30  that is connected to an input of a low prime oxygenator  32 . Blood is perfusion with oxygen within the oxygenator  32  and passed therefrom through a fourth conduit  34  to an arterial filter  36 . The oxygenated blood continues through the arterial filter  36  to an arterial return line  38  that terminates in an arterial cannula (not shown) in the patient. Other components, such as a bubble detector  39 , may be provided in the return line  38 , as is well known in the art.  
         [0027]    Adult Heat Exchanger/Reservoir  
         [0028]    [0028]FIG. 2 is a cross sectional view through an exemplary heat exchanger/reservoir  40  sized for use in an adult extracorporeal circuit. The heat exchanger/reservoir  40  comprises a lower housing  42  topped by a lid  44 . The housing  42  comprises a slightly upwardly and outwardly tapered cylindrical outer wall  46  and a reservoir floor  48  that, together with the lid  44 , define within a reservoir chamber  52 . The heat exchanger/reservoir  40  may be adapted in conventional ways to be secured in a location adjacent to an operating table.  
         [0029]    An elongated, conical, central spacer  56  extends upward from the reservoir floor  48  into proximity with the lid  44 . The central spacer  56  is preferably concentrically positioned within the outer wall  46  to define an inner boundary of the reservoir chamber  52 . The reservoir chamber  52  thus comprises a tall, generally annular space defined within the housing  42 .  
         [0030]    The lid  44  includes an outer flange  58  surrounding the top rim of the outer wall  46 . An O-ring  60  provides a seal between the housing  42  and lid  44 . Inward from the flange  58 , the lid  44  includes an upwardly projecting first turret  62 , and a second smaller turret  64  formed above the first turret. The second turret  64  has a central opening in a top wall for receiving a venous inlet fitting  66 . The fitting  66  extends upward and branches outward into a venous inlet port  68 , and an upper sampling port  70 . A third aperture may be provided in the fitting  66  to receive an inlet blood temperature probe  72 . The venous inlet fitting  66  extends downward into a space created within the upper turret  64  and bounded on the bottom side by a conical flow guide  74 . An annular debubbler filter  76  is provided within the space in the upper turret  64 . One or more cardiotomy inlets  78  may also be provided in the side wall of the upper turret  64 .  
         [0031]    The reservoir  40  may be adapted for conventional venous gravity drainage wherein a gas vent  79  in the lid  44  remains open. In this mode, the chamber  52  is not sealed from the outside atmosphere. More recently, advances in minimally invasive surgical techniques have dictated the use of smaller and smaller venous cannulae, and a negative pressure in the venous return line may be advantageous. In this mode, a source of vacuum may be connected with the chamber  52  to help pull venous blood from the patient, such as by attaching a vacuum line (not shown) to the gas vent  79 . This seals the chamber  52  from the outside atmosphere and creates a negative pressure within.  
         [0032]    A plurality of heat exchange chamber inlets  80  are provided between the outer edges of the flow guide  74  and an internal corner formed between the first and second turrets  62 ,  64 . The inlets  80  may be a regular series of apertures, or slots, or may be formed by an annular space surrounding the flow guide  74  interrupted by spokes connecting the flow guide with the lid  44 .  
         [0033]    A generally cylindrical inner heat exchange chamber wall or guide  82  extends downward from the flow guide  74  into the reservoir chamber  52 . The inner heat exchange guide  82  is concentrically spaced around the central spacer  56 . A generally cylindrical outer heat exchange guide  84  depends downward from the first turret  62  to concentrically surround the inner heat exchange guide  82 , and defines an annular heat exchange chamber  86  therebetween. A plurality of heat exchange elements or coils  88  internally defining one or more fluid flow paths are helically disposed in the annular heat exchange chamber  86 . Preferably, a single heat exchange inlet conduit  90 , in cooperation with an outlet heat exchange conduit (not shown), supplies a flow of heat transfer medium to the interior of the coils  88 . In the preferred embodiment, the heat transfer medium is water, although other mediums are contemplated.  
         [0034]    The annular heat exchange chamber  86  defined between the guides  82 ,  84  extends downward from the lid  44  a substantial distance toward the reservoir floor  48 . In a preferred embodiment, the guides  82 ,  84  terminate at a heat exchange outlet  92  that is located above the reservoir floor  48  a distance of approximately ¼ of the total height of the reservoir chamber  52 . This relative distance may be modified depending on the total volume of the reservoir chamber  52 , and its radial dimensions.  
         [0035]    A large defoamer element  100  closely surrounds the outer heat change guide  84 . The defoamer element  100  continues radially inward underneath the annular heat exchange chamber  86  into contact with the central spacer  56 . The defoamer element  100  may be a variety of constructions, but is preferably a polymer mesh treated with a defoaming substance. A support sleeve  102  surrounds and contains the defoamer element  100 . The support sleeve  102  desirably rigidly attaches at the top to the lid  44 , and at the bottom to the central spacer  56 , or to the reservoir floor  48 . The support sleeve  102  may take a variety of forms, but is preferably a plastic member having a grid-like or otherwise perforated configuration. An outer polyester filter or sock  104  surrounds the supports sleeve  102  and contains a non-woven filter  106  around the lower end thereof. The non-woven filter  106  has a cup shape and extends upward above the heat exchange outlet  92 .  
         [0036]    The reservoir floor  48  defines a peripheral flow channel  110  which gradually transitions into a deep drain well  112  on one circumferential side. A number of apertures are formed in the housing adjacent the drain well  112 . Namely, a lower sampling port  114 , a hemo concentration line  116 , and a blood outlet port  118 , all communicate through the apertures with the drain well  112 . A fourth aperture may receive a lower blood temperature probe  120 .  
         [0037]    Operation of Adult Heat Exchanger/Reservoir  
         [0038]    In operation, venous blood enters the heat exchanger/reservoir  40  through the venous inlet port  68 . The venous blood travels downward through the fitting  66  and radially outward through the debubbler filter  76  as indicated by the flow arrows  130 . Fluid aspirated through the cardiotomy lines enters through the cardiotomy inlets  78  and passes through the debubbler filter  76  as indicated by the flow arrows  132 . In this manner, venous inlet blood does not mix with cardiotomy fluid before passing through the debubbler filter  76 .  
         [0039]    The cardiotomy fluid and venous blood pass downward through the heat exchange chamber inlets  80  into the annular heat exchange chamber  86 . The blood then flows by gravity (or under the influence of a slight vacuum, if vacuum-assisted venous drainage is desired) across the heat exchange coils  88  in a single pass, as indicated by flow arrows  134 . The heat treated blood exits the heat exchange chamber  86  into the reservoir chamber  52  through the heat exchange outlet  92 . After passing through the heat exchange chamber  86 , blood continues downward and outward through the defoamer element  100 , support sleeve  102 , non-woven filter  106 , and polyester filter  104 , into the space between the polyester filter and the outer wall  46 . The blood level under the heat exchange chamber  86  and within the sock  104  may reach or exceed that of the heat exchange outlet  92 , but desirably does not crest over the top edge of the non-woven filter  106  to ensure proper filtration. The blood then continues through the flow channel  110  into the drain well  112 , and out through the outlet port  118 .  
         [0040]    One advantage of the present heat exchanger/reservoir  40  is the provision of a separate heat exchange chamber  86  within the reservoir. With such an arrangement, the ratio of the surface area of the heat exchange coils  88  to the volume of blood in the heat exchange chamber  86  is maximized, and the blood is guided across every coil. The performance of the heat exchanger is thus not dependent on the level of blood within the reservoir. As will be appreciated by those of skill the art, separate heat exchange chambers within the reservoir other than the annular columnar embodiment shown may be equally effective as long as the result is to decouple the heat exchange efficiency from the reservoir blood level. In addition, heat transfer elements other than the coils shown may be used, such as fins or straight tubes.  
         [0041]    Adult Low Prime Oxygenator  
         [0042]    As seen FIG. 1, a blood pump  28  impels blood from port  118  to a blood oxygenator  32 . Although the previously described heat exchanger/reservoir  40  may be coupled with a variety of oxygenators, a particularly preferred oxygenator  150  is seen in FIGS. 3 and 3 a . The oxygenator  150  is a low prime membrane oxygenator having a single blood inlet and outlet, and single gas inlet and outlet.  
         [0043]    As seen exploded in FIG. 3 a , the main components of the oxygenator  150  comprise a central, cylindrical housing  152 , a top cap  154  on one axial end of the housing, and a bottom cap  156  and a blood inlet cap  158  on an opposite axial end of the housing. The housing  152  is preferably cylindrical, but may be other shapes, and is concentrically disposed about an axis (not shown). The components of the housing  152 , top cap  154 , bottom cap  156 , and blood inlet cap  158 , are preferably molded of plastic, biocompatible materials. Biocompatible coatings, such as Duraflo® available from Baxter Healthcare Corporation, may be provided on the plastic components of the oxygenator  150  to reduce blood interactions.  
         [0044]    One primary advantage of the oxygenator  150  is the small number of parts. In addition to those mentioned above, the only other components of the oxygenator  150  are a plurality of hollow, semi-permeable fibers  160  (partially shown in the chamber  168 ) extending generally axially within housing  152 , and potting regions  170 ,  172  at both ends of the fibers and housing. The respective components, except the hollow fibers  160 , are easily molded and attached together using a variety of means. For instance, the mating parts may be provided with interfering ribs or latches in conjunction with a sealing mechanism, such as O-rings, to enable a snap-fit assembly. Alternatively, the parts may be more permanently bonded together, such as with a biocompatible adhesive, or, more preferably, with ultraviolet (UV) welding.  
         [0045]    The specific structural attributes of the low prime oxygenator  150  will now be described in more detail. The central housing  152  comprises an outer wall  164  concentrically disposed about an inner wall  166 . An elongated annular oxygenation chamber  168  is defined between the inner surface of the outer wall  164  and the outer surface of the inner wall  166 . The hollow fibers  160  extend generally axially within the oxygenation chamber  168  and are rigidly secured within the chamber between an upper potting region  170 , and a lower potting region  172 . The potting regions  170  and  172  delimit the oxygenation chamber  168  at each axial end. As is well-known in the art, the hollow fibers  160  are positioned and secured with potting material at both ends, which material is then severed perpendicular to the axis to expose open ends of each individual fiber. The potted bundle of fibers  160  is then sealed in place flush with both ends of the housing  152 . The housing  152  further includes a bottom wall  174  extending across, and preferably molded integrally with, the inner wall  166  at a distance from the lower extremity of the housing.  
         [0046]    The top cap  154  comprises a top wall  180  having a peripheral side wall  182  joined thereto. As seen in FIG. 3, the top cap  154  fits over the top end of the housing  152  so that mating portions of the side wall  182  and outer wall  164  are in registry. More specifically, an inner shoulder  184  in the top cap  154  contacts a step  186  at the top end of the outer wall  164 . In addition, a portion of the side wall  182  extends around a small flange  188 , and a skirt  190  extends downward around and in contact with a large flange  192 .  
         [0047]    With reference to FIG. 3, a blood outlet manifold is defined within the top cap  154  and outside of the housing  152 . More specifically, the side wall  182  defines a small annular space  200  adjacent the small flange  188 . The small flange  188  and annular space  200  extend substantially around the periphery of the housing  152 . The skirt  190  comprises an outwardly bulged portion on one side of the side wall  182  and defines a larger space  202 . The smaller space  200  and larger space  202  are in fluid communication to define the blood outlet manifold surrounding a plurality of oxygenation chamber outlets  204 . A recirculation port  206  extends radially outward from the side wall  182  at a location that is diametrically opposed to the large space  202  and a blood outlet port  208  extending radially outward from the skirt  190 . An aperture  210  may be provided in the top cap  154  to receive a temperature probe  212  for measuring the temperature of blood within the large space  202 .  
         [0048]    The top wall  180  of the top cap  154  is shaped to define an annular gas header space  220  adjacent the upper potting region  170  and sealed from the blood outlet manifold. A gas inlet port  222  in the center of the top cap  154  opens into a large central gas manifold bordered by the inner wall  166 , bottom wall  174 , and top cap  154 . The open ends of the hollow fibers  160  adjacent the gas header space  220  are in fluid communication with this gas chamber.  
         [0049]    Still with reference to FIG. 3 a , the bottom cap  156  comprises a bottom wall  230 , an inner skirt  232 , and an outer skirt  234 . The inner wall  166  of the housing  152  includes a lower cylindrical portion  236  below the bottom wall  174 . A number of circumferential slots or apertures define oxygenation chamber inlets  238  between this lower portion  236  and the bottom wall  174 . Although not shown, the lower portion  236  is desirably integrally molded with the inner wall  166  and bottom wall  174  to define an inner core of the housing  152 . The bottom cap  156  fits over the lower end of the housing  152  with the inner skirt  232  in sealed contact with the lower portion  236 , and the outer skirt  234  surrounding and in sealed contact with the outer wall  164 . The bottom wall  230  of the bottom cap  156  is spaced from the lower potting region  172  to define an annular lower manifold  239  (FIG. 3) in fluid communication with the open ends of the hollow fibers  160  secured within the lower potting region  172 . A gas outlet port  240  also in fluid communication with the manifold  239  extends downward from the bottom wall  230  on one side thereof.  
         [0050]    The blood inlet cap  158  comprises a radially disposed circular flange  242  and an axial blood inlet port  244 . The flange  242  fits snugly within the inner surface of the lower portion  236  of the inner wall  166  and is secured thereto. The flange  242  is thus spaced from the bottom wall  174  to define a blood distribution space  246  therebetween, with the chamber inlets  238  desirably evenly arranged around the distribution space circumference.  
         [0051]    The adult oxygenator  150  preferably has a prime volume of between 130-180 ml.  
         [0052]    Operation of the Adult Low Prime Oxygenator  
         [0053]    With reference to FIG. 3, the respective blood and gas flows through the oxygenator  150  are shown. Blood enters through the central lower inlet port  244  and is evenly distributed radially outward in all directions in the space  246 . The blood passes outward through the chamber inlets  238  into the oxygenation chamber  168 . As seen by the nonlinear blood flow arrows  250 , blood passes upward through the chamber  168  in the spaces formed between the hollow fibers  160 .  
         [0054]    In a preferred embodiment, the hollow fibers  160  are arranged in sequential layers of fiber mats, with the fibers in adjacent mats being helically angled with respect to each other. In a first example, the angle of fibers in each mat is in the same helical sense, while in a second example, the angle of fibers in adjacent mats are in the opposite helical sense. In the former example, the blood passes between the fibers in a generally helical path through the oxygenation chamber  168 , while in the latter example, the blood passes between the fibers in a zigzag fashion from one end of the chamber  168  to the other. Various configurations of hollow fiber architectures are available for use with the low prime oxygenator, such as for example in PCT publication No. WO 97/08933, which is hereby expressly incorporated by reference. Exemplary hollow fiber architectures are shown and described in more detail with respect to FIGS. 6 a  and  6   b.    
         [0055]    Blood flows through the chamber  168  as shown by the arrows  250  from the inlets  238  to the outlets  204 . As mentioned above, the inlets  238  and outlets  204  are provided around substantially the entire circumference of the housing  152  to help ensure even distribution of the blood flow within the chamber  168 . Because of the circular disposition of the inlets  238  and outlets  204 , the blood flows substantially axially within the chamber  168  past the hollow fibers  160 . The now oxygenated blood fills the annular region defined by the spaces  200  and  202  and is available for outlet through the recirculation port  206  and/or blood outlet port  208 .  
         [0056]    Gas flows into the oxygenator  150  through inlet port  222  and into the region in communication with the gas header space  220 . As mentioned, the hollow fibers  160  are open at the top end of the upper potting region  170  and the gas flows into the hollow fibers and continues through the fiber lumens to the lower manifold  239 . The inlet gas is preferably pure or nearly pure oxygen which permeates outward through the semi-permeable tubular wall of each individual hollow fiber  160  into the blood which is passing in a counter direction, thus raising the oxygen partial pressure of the blood. The impetus for the migration of gas molecules through the tubular fiber walls is a differential partial pressure of each respective gas. Carbon dioxide permeates inwardly from the blood into each individual fiber lumen, thus lowering the carbon dioxide partial pressure of the blood. The end result is that the blood absorbs oxygen and gives off carbon dioxide into the gas stream. The gas exits the open ends of hollow fibers  160  into the lower manifold  239  and is exhausted through the gas outlet port  240 .  
         [0057]    Neonatal/Infant Heat Exchanger/Reservoir  
         [0058]    [0058]FIG. 4 is a cross sectional view through an exemplary heat exchanger/reservoir  340  sized for use in an neonatal/infant extracorporeal circuit. The reservoir  340  is similar in many respects to the adult reservoir  40  described above, and as such, like elements are numbered in parallel in the  300  and  400  range and may not be described in as great detail.  
         [0059]    The heat exchanger/reservoir  340  comprises a lower housing  342  topped by a lid  344 . The housing  342  comprises a slightly upwardly and outwardly tapered cylindrical outer wall  346  and a reservoir floor  348  that, together with the lid  344 , define within a reservoir chamber  352 . An O-ring  360  provides a seal between the housing  342  and lid  344 . Conventional mounting means may be provided to secure the heat exchanger/reservoir  340  in a location adjacent to an operating table. In contrast to the adult reservoir  40  described above, the neonatal/infant reservoir  340  does not include a central conical spacer, and the reservoir chamber  352  thus comprises a generally cylindrical volume defined within the housing  342 .  
         [0060]    As before, the lid  344  includes an upwardly projecting first turret  362 , and a second smaller turret  364  formed above the first turret. The second turret  364  has a central opening in a top wall for receiving a venous inlet fitting  366  that extends upward and branches outward into a venous inlet port  368 , and an upper sampling port  370 . A third aperture may be provided in the fitting  366  to receive an inlet blood temperature probe  372 . The venous inlet fitting  366  extends downward into a space created within the upper turret  364  and bounded on the bottom side by a conical flow guide  374 . An annular debubbler filter  376  is provided within the space in the upper turret  364 . One or more cardiotomy inlets  378  may also be provided in the side wall of the upper turret  364 .  
         [0061]    The reservoir  340  may be adapted for conventional venous gravity drainage in which a gas vent  379  in the lid  344  is open so that the chamber  352  is not sealed from the outside atmosphere. Alternatively, a vacuum line (not shown) may be attached to the gas vent  379  which seals the chamber  352  from the outside atmosphere and creates a negative pressure within to help pull venous blood from the patient.  
         [0062]    A plurality of heat exchange inlets  380  are provided between the outer edges of the flow guide  374  and an internal comer formed between the first and second turrets  362 ,  364 . As in the earlier embodiment, the inlets  380  may be a regular series of apertures, or slots, or may be formed by an annular space surrounding the flow guide  374  interrupted by spokes connecting the flow guide with the lid  344 .  
         [0063]    A generally cylindrical inner heat exchange chamber wall or guide  382  extends downward from the flow guide  374  into the reservoir chamber  352 . The inner heat exchange guide  382  is concentrically spaced within the outer wall  346 . A generally cylindrical outer heat exchange guide  384  depends downward from the first turret  362  to surround the inner heat exchange guide  382  and define an annular heat exchange chamber  386  therebetween. A plurality of heat exchange elements or coils  388  internally defining one or more fluid flow paths are helically disposed in the annular heat exchange chamber  386 . Preferably, a single heat exchange inlet conduit  390 , in cooperation with an outlet heat exchange conduit (not shown), supplies a flow of heat transfer medium to the interior of the coils  388 .  
         [0064]    The annular heat exchange chamber  386  defined between the guides  382 ,  384  extends downward from the lid  344  a substantial distance toward the reservoir floor  348 . In a preferred embodiment, the guides  382 ,  384  terminate at a heat exchange outlet  392  that is located above the reservoir floor  348  a distance of approximately ¼ of the total height of the reservoir chamber  352 . Again, this relative distance may be modified depending on the total volume of the reservoir chamber  352 , and its radial dimensions, and may be different from the configuration of the adult reservoir  40 .  
         [0065]    The neonatal/infant reservoir  340  includes a series of concentric filters surrounding the heat exchange chamber  386  as described previously. Thus, the reservoir  340  preferably includes a large defoamer filter  400  surrounded by a support sleeve  402 , with an outer polyester sock  404  and a non-woven filter  406  around the lower end thereof. The non-woven filter  406  extends above the height of the heat exchange outlet  392  proportionally higher in the neonatal/infant reservoir  340  than in the adult reservoir  40 .  
         [0066]    The reservoir floor  348  defines a flow channel  410  that provides a gradual transition from the floor to a deep drain well  412 . A number of apertures may be formed in the housing adjacent the drain well  412 , although only a blood outlet port  418  is shown.  
         [0067]    Operation of the Neonatal/Infant Heat Exchanger/Reservoir  
         [0068]    The operation of the neonatal/infant reservoir  340  is as described above with respect to the adult reservoir  40 , with venous blood entering through the venous inlet port  368  and exiting from the lower outlet  418 . As before, venous inlet blood does not mix with cardiotomy fluid before passing through the debubbler filter  376 .  
         [0069]    Within the chamber  352 , cardiotomy fluid and venous blood pass downward through the heat exchange inlets  380  into the annular heat exchange chamber  386 . The blood then flows by gravity over the exchange coils  388  in a single pass, as indicated by flow arrows  434 , and exits into the reservoir chamber  352  through the heat exchange outlet  392 . After passing through the heat exchanger, blood continues downward and outward through the defoamer element  400 , support sleeve  402 , non-woven filter  406 , and polyester filter  404 , into the space between the polyester filter and the outer wall  346 . The increased height of the top edge of the non-woven filter  406  is needed to prevent cresting and ensure proper filtration of the blood because of the smaller volume, and thus more variable blood level in the reservoir chamber  352 . After being filtered, the blood then continues through the flow channel  410  and into the drain well  412 .  
         [0070]    Neonatal/Infant Low Prime Oxygenator  
         [0071]    As seen in FIG. 1, a blood pump  28  impels the blood from reservoir outlet port  418  to a blood oxygenator  32 . Although the previously described heat exchanger/reservoir  340  may be coupled with a variety of oxygenators, a particularly preferred oxygenator  450  suitable for use with neonatals or infants is seen in FIGS.  5  and  5   a . The oxygenator  450  is similar in many respects to the adult oxygenator  150  described above, and as such, like elements are numbered in parallel in the 400 and 500 range and may not be described in as great detail.  
         [0072]    As seen exploded in FIG. 5 a , the main components of the oxygenator  450  comprise a central, cylindrical housing  452 , a top cap  454  on one axial end of the housing, and a bottom cap  456  and a blood inlet cap  458  on an opposite axial end of the housing. The housing  452  is preferably cylindrical, but may be other shapes, and is concentrically disposed about an axis (not shown). The components of the housing  452 , top cap  454 , bottom cap  456 , and blood inlet cap  458 , are preferably molded of plastic, biocompatible materials. Biocompatible coatings, such as Duraflo® available from Baxter Healthcare Corporation, may be provided on the plastic components of the oxygenator  450  to reduce blood interactions.  
         [0073]    As in the earlier embodiment, the oxygenator  450  has a very small number of parts for ease of manufacture and assembly. In addition to those mentioned above, the only other components of the oxygenator  450  are a plurality of hollow, semi-permeable fibers  460  extending generally axially within housing  452 , and potting regions at both ends of the fibers and housing. The respective components, except the hollow fibers  460 , are easily molded and attached together using a variety of means. For instance, as described above, a snap-fit assembly, biocompatible adhesive, or, more preferably, ultraviolet (UV) welding may be utilized.  
         [0074]    The central housing  452  comprises an outer wall  464  concentrically disposed about an inner wall  466 . An elongated annular oxygenation chamber  468  is defined between the inner surface of the outer wall  464  and the outer surface of the inner wall  466 . The hollow fibers  460  extend generally axially within the oxygenation chamber  468  and are rigidly secured within the chamber between an upper potting region  470 , and a lower potting region  472 . The housing  452  further includes a bottom wall  474  extending across the inner wall  466  and spaced from the lower extremity of housing.  
         [0075]    The top cap  454  comprises a top wall  480  having a peripheral side wall  482  joined thereto. As seen in FIG. 5 a , the top cap  454  fits over the top end of the housing  452  so that an inner shoulder  484  in the top cap  454  contacts a step  486  at the top end of the outer wall  464 . In addition, a portion of the side wall  482  extends around a small flange  488 , and a skirt  490  extends downward around and in contact with a large flange  492 .  
         [0076]    As in the first embodiment, and with reference to FIG. 5, a blood outlet manifold is defined within the top cap  454  and outside of the housing  452 . More specifically, the side wall  482  is shaped to define a small annular space  500  between a plurality of oxygenation chamber outlets  504  and a recirculation port  506 . A skirt  490  comprises an outwardly bulged portion on one side of the side wall  482  and defines a larger space  502  between the oxygenation chamber outlets  504  and a blood outlet port  508  extending radially outward from the skirt  490 . The smaller space  500  and larger space  502  are in fluid communication to define the blood outlet manifold surrounding the oxygenation chamber outlets  504 . An aperture may be provided in the top cap  454  to receive a temperature probe  512  for measuring the temperature of blood within the large space  502 .  
         [0077]    The top wall  480  of the top cap  454  is shaped to define an annular gas header space  520  adjacent the upper potting region  470  and sealed from the blood outlet manifold. A gas inlet port  522  in the center of the top cap  454  opens into a large central gas manifold bordered by the inner wall  466 , bottom wall  474 , and top  454 . The open ends of hollow fibers  460  adjacent the gas header space  520  are in fluid communication with this gas chamber.  
         [0078]    Still with reference to FIG. 5 a , a number of circumferential slots or apertures in the inner wall  466  define oxygenation chamber inlets  538 . The bottom cap  456  fits over the lower end of the housing  452  with an inner skirt  532  in sealed contact with the lower portion of the inner wall, and an outer skirt  534  surrounding and in sealed contact with the outer wall  464 . The bottom cap  456  is spaced from the lower potting region  472  to define an annular lower manifold  539  (FIG. 5) in fluid communication with the open ends of the hollow fibers  460  secured within the lower potting region  472 . A gas outlet port  540  in fluid communication with the manifold  539  extends downward from the bottom cap  456  on one side thereof.  
         [0079]    The blood inlet cap  458  comprises a radially disposed circular flange  542  and an axial blood inlet port  544 . The flange  542  fits snugly within the lower portion of the inner wall  466  and is secured thereto. The flange  542  is thus spaced from the bottom wall  474  defining a blood distribution space  546  therebetween, with the chamber inlets  538  desirably evenly arranged around the distribution space circumference.  
         [0080]    The neonatal/infant oxygenator  450  preferably has a prime volume of between 56-80 ml.  
         [0081]    Operation of the Neonatal/Infant Low Prime Oxygenator  
         [0082]    With reference to FIG. 5, the respective blood and gas flows through the oxygenator  450  are shown. Blood enters through the lower inlet port  544  and is evenly distributed radially outward in all directions in the space  546 . The blood passes outward through the chamber inlets  538  into the oxygenation chamber  468 . As seen by the nonlinear blood flow arrows  550 , blood passes upward through the chamber  468  in the spaces formed between hollow fibers  460 .  
         [0083]    The blood flows substantially axially through the chamber  468  as shown by the arrows  550  from the inlets  538  to the outlets  504  and is evenly distributed therein by the circular arrangement of the inlets and outlets.  
         [0084]    Gas flows into the oxygenator  450  through inlet port  522  and into the region in communication with the gas header space  520 . Oxygen permeates outward through the semi-permeable tubular wall of each individual hollow fiber  460  into the blood that is passing in a counter direction, while carbon dioxide permeates inwardly from the blood into each individual fiber lumen. The gas exits the open ends of hollow fibers  460  into the lower manifold  539  and is exhausted through the gas outlet port  540 .  
         [0085]    Hollow Fiber Architecture  
         [0086]    Of course there are a number of different configurations of hollow fibers that may be used with the present oxygenators, but a particular preferred arrangement of layered sheets of fibers produces optimum performance. With reference to FIGS. 6 a  and  6   b , two exemplary embodiments of layered sheets of fibers are shown. Both of these embodiments show layers of fibers being spirally wrapped around a cylindrical core  600 , which is removed after an annular fiber bundle is assembled. Alternatively, the layers of hollow fibers may be spiral wound around the inner wall  166  or  466  of one of the two oxygenators, prior to assembling the outer wall thereover. For the sake of manufacturing efficiency, however, a separate core is used to wind the layers of fibers, which are then removed and separately assembled with the other oxygenator parts. Those skilled in the art will recognize that various fabrication methods are possible.  
         [0087]    In FIG. 6 a , a first layer  602  and a second layer  604  are wound around the core  600 . Both the first and second layers  602 ,  604  comprise a plurality of hollow fibers joined together in a parallel, spaced array with monofilaments, or other similar expedient. A first plurality of fibers  606  in the first layer  602  are arranged at an angle with respect to the axis of the core, while a second plurality of fibers  608  in the second layer  604  are arranged at a different angle. The angles that both the first and second pluralities of fibers  606 ,  608  make with the axis are in the same rotational sense, and are preferably less than  45 °. Furthermore, the angles the two fiber pluralities make are desirably within 15° of each other, more desirably about 9°, as shown. When the complete fiber bundle has been wound and assembled in the oxygenator, the layers are spirally wound, while the individual fibers are helically wound. In the embodiment of FIG. 6 a , blood flow through the oxygenation chamber will follow a non-linear path between the alternately angled fibers, and will generally be guided helically around the annular space.  
         [0088]    In contrast, the embodiment of FIG. 6 b  includes a first fiber layer  610  and a second fiber layer  612 , wherein a first plurality of fibers  614  and a second plurality of fibers  616  are angled in the opposite rotational sense around the core  600 . Again, the angles that both the first and second pluralities of fibers  614 ,  616  make with the axis are preferably less than 45°, and desirably the included angle therebetween is about 90°. This arrangement induces non-linear and generally axial flow of blood between the alternately angled fibers.  
         [0089]    In both fiber embodiments shown in FIGS. 6 a  and  6   b , the two layers of fibers are desirably joined together in a mat prior to spirally winding them about the core. That is, the two joined layers comprise a mat that is then spirally wound in the core. This mat is preferably assembled well before the oxygenator assembly, which facilitates automation and the rapid manufacture of the present oxygenator. One suitable source of such fiber layers is Akzo Nobel N.V. of Arnhem, Netherlands, although other sources are available.  
         [0090]    Low Prime Extracorporeal Circuit  
         [0091]    The present invention provides improvements over prior extracorporeal circuits by having a very low prime volume and high oxygenation performance. The very low prime volume allows for the use of a single size of oxygenator for a much larger range of patient weights, not possible with oxygenators presently on the market having equivalent oxygenation capacity. Therefore, the two sizes of oxygenator shown herein are sufficient to cover a range of patients from neonatal to adults weighing in excess of 300 pounds (140 kg). More specifically, the neonatal/infant oxygenator  450  shown and described with respect to FIGS. 5 and 5 a  is designed for use in extracorporeal circuits for patients ranging from neonatals up to patients weighing about 44 pounds (20 kg). The adult oxygenator  150  in FIGS. 3 and 3 a  is designed for use in extracorporeal circuits for patients ranging in weight from about 44 pounds (20 kg) to about 308 pounds (140 kg).  
         [0092]    A number of factors contribute to make the oxygenator of the present invention superior from those currently available. Some of these factors include the removal of the heat exchanger from incorporation in the oxygenator to the reservoir, the particular geometry of the oxygenator, and a hollow fiber architecture which is particularly well-suited to function within and complement the specific oxygenation chamber design. The advantages of removing the heat changer from the oxygenator have been described above. A detailed description of the particular geometry of the improved oxygenator follows.  
         [0093]    With reference to FIG. 7, the adult low prime oxygenator  150  previously described with reference to FIGS. 3 and 3 a  is shown with various key dimensions indicated. The oxygenation chamber  168  is defined between the outer diameter D 1  of the inner wall  166  and the inner diameter D 2  of the outer wall  164 . H indicates the common length of both the outer wall  164  and inner wall  166 , while the length between the two potting regions  170  and  172  is indicated as h. Therefore, the oxygenation chamber  168 ,  468  has a height h. A number of cross-sectional areas derived from the axial and radial dimensions, are defined as follows, with the first three being taken normal to the axis of the cylindrical walls:  
         [0094]    A 1 =the annular area of the oxygenation chamber  
         [0095]    A 2 =the aggregate area within the hollow fibers  
         [0096]    A 3 =the area of the blood flow within the oxygenation chamber  168  (i.e., the area outside of the hollow fibers)  
         [0097]    A 4 =the total area of the oxygenation chamber inlets  238   
         [0098]    A 5 =the total area of the oxygenation chamber outlets  204   
         [0099]    A 6 =the cross-sectional area of the blood inlet and outlet connectors  
         [0100]    A 7 =the aggregate effective external surface area of the hollow fibers in the oxygenation chamber  
         [0101]    From the above dimensions, a number of volumes may be calculated as follows:  
         [0102]    V 1 =the volume between the inner and outer walls without the potting regions  170 ,  172   
         [0103]    V 2 =the volume between the inner and outer walls without the potting regions, and outside the hollow fibers  
         [0104]    V 3 =the volume occupied by the aggregate fibers without the potting regions  
         [0105]    V 4 =the volume occupied by the aggregate fibers between the potting regions  
         [0106]    V 5 =the priming volume of the top cap  154   
         [0107]    V 6 =the priming volume of the blood distribution space  246   
         [0108]    v 1 =the volume between the inner and outer walls and the potting regions  
         [0109]    v 2 =the volume between the inner and outer walls and the potting regions, and outside the hollow fibers (static priming volume)  
         [0110]    A number of mathematical relations between these geometries may be stated:  
           A 1 =A   2   +A   3 =π/4( D   2   2   −D   1   2 )  
         
       V 
       1 
       =A 
       1 
       ×H=V 
       2 
       +V 
       3  
     
         
       v 
       1 
       =A 
       1 
       ×h=v 
       2 
       +V 
       4  
     
         [0111]    The preferred relationships between the geometric parameters for the adult low prime oxygenator  150  described with respect to FIGS. 3 and 3 a  are as follows (it should be noted that the corresponding units can be found in Table II, and any necessary conversions are implicit in the RESULT column):  
                       TABLE I                       CORRELATION   CALCULATION   RESULT                   D 2  with D 1     (D 2   2  − D 1   2 ) × π/4   24 ≦ A 1  ≦ 28       A 1  with H   A 1 × H     370 ≦ V 1  ≦ 410       A 1  with H   H/A 1     5 ≦ H/A 1  (mm/cm 2 ) ≦ 6       v 1  with V 4     v 1  − V 4     130 &gt; v 2  ≦ 180       v 1  with V 4     V 4 /v 1     0.5 ≦ V 4 /v 1  ≦ 0.6                  
 
         [0112]    It will also be understood that the preferred ranges given in Table I (and the other tables herein) are specific to the metric units used in the example, but are translatable to other units with appropriate calculations which would be apparent to those skilled in the art. For example, the first calculation of Al would have a different result if inches were the units; as in the following calculation with preferred dimensions:  
           D   1 =85 mm=3.35 in  
           D   2 =62 mm=2.44 in  
           A   1 =( D   2   2   −D   1   2 )×π/4=4.14 in  
         [0113]    Therefore, the ranges given above must be converted to appropriate units, but represent optimum geometrical relations which ensure a relatively high oxygen transfer rate and blood flow in an oxygenator with a low prime volume. One important parameter represented in Table I is the ratio of the volume of the aggregate fibers (V 4 ) to the volume between the inner and outer walls (v 1 ). That is, how much space does the fiber take up within the blood chamber, or, conversely, how much space is allowed for blood flow? This ratio (V 4 /v 1 ) in relation to the absolute difference in the volumes (v 1 −V 4 ) is one reason for the enhanced performance of the present oxygenator.  
         [0114]    The following table shows a range of exemplary values as well as a particularly preferred value of the above parameters for the adult low prime oxygenator  150 .  
                                                 TABLE II                                   ACTUAL   RANGE                                        A 1     26.9   cm 2     24-28           A 2     15.5   cm 2     14-17           A 3     11.3   cm 2     10-13           A 4     8.4   cm 2      7-10           A 5     9.5   cm 2      8-11           A 6     0.7   cm 2     0.5-0.8           A 7     2.0   m 2     1.9-2.0           D 1     61.7   mm   60-63           D 2     85.0   mm   83-87           H   145.0   mm   143-147           h   125.0   mm   110-130           V 1     389.3   ml   370-410           v 1     335.6   ml   320-360           V 2     156.4   ml   140-180           v 2     149.3   ml   130-180           V 3     232.9   ml   210-250           V 4     186.3   ml   170-210           V 5     8.1   ml    6-10           V 6     6.5   ml   5-9                      
 
         [0115]    Similar considerations for the adult low prime oxygenator are shared by the neonatal/infant low prime oxygenator  450  described with respect to FIGS. 5 and 5 a . The preferred relationships between the geometric parameters are modified for this smaller size oxygenator as follows (again, the corresponding units can be found in Table IV, and any necessary conversions are implicit in the RESULT column):  
                       TABLE III                       CORRELATION   CALCULATION   RESULT                   D 2  with D 1     (D 2   2  − D 1   2 ) × II/4   24 ≦ A 1  ≦ 28       A 1  with H   A 1 × H     200 ≦ V 1  ≦ 240       A 1  with H   H/A 1     2.5 ≦ H/A 1  (mm/cm 2 ) ≦ 3.5       v 1  with V 4     v 1  − V 4     56 &gt; v 2  ≦ 80       v 1  with V 4     V 4 /v 1     0.5 ≦ V 4 /v 1  ≦ 0.6                  
 
         [0116]    The following table shows a range of exemplary values and a particularly preferred value for the various parameters in the neonatal/infant low prime oxygenator  450 .  
                                                 TABLE IV                                   ACTUAL   RANGE                                        A 1     26.9   cm 2     24-28           A 2     15.5   cm 2     14-17           A 3     11.3   cm 2     10-13           A 4     4.2   cm 2     3-6           A 5     4.1   cm 2     3-6           A 6     0.3   cm 2     0.2-0.4           A 7     1.0   m 2     0.9-1.0           D 1     61.7   mm   60-63           D 2     85.0   mm   83-87           H   81.0   mm   79-83           h   60.0   mm   58-62           V 1     217.5   ml   200-240           v 1     161.1   ml   140-180           V 2     87.5   ml    70-100           v 2     70.4   ml   56-80           V 3     129.9   ml   120-140           V 4     90.6   ml    80-100           V 5     8.1   ml    6-10           V 6     6.5   ml   5-9                      
 
         [0117]    A comparison of the present adult oxygenator  150  with oxygenators of similar capacity is given in the following chart:  
                                                                                           TABLE V                           PERFORMANCE COMPARISON OF ADULT MEMBRANCE OXYGENATORS                    HOLLOW   ARTERIAL                                   FIBER   O 2                 EFFEC-   PARTIAL   O 2  XFER ≧   CO 2  XFER ≧   PRESSURE               TIVE   PRESSURE   50   42   DROP       H.E.               SURFACE   (mmHg) (at   ml/min/lpm   ml/min/lpm   (mmHg) (at   PRIME   PERFOR-               AREA   7 lpm blood   (at 7 lpm   (at 7 lpm   7 lpm blood   VOLUME   MANCE       MFG   MODEL   (m 2 )   flow)   blood flow)   blood flow)   flow)   (ml)   FACTOR                    MACCHI   Present   0.7   248   57.5   55   137   170   0.48           Invention       BENTLEY   SPIRAL   1.9   209   57.7   52   69   265   0.48           GOLD       SARNS   SARNS   1.9   310   57.7   58   270   270   0.65           TURBO       MEDTRO-   MAXIMA   2.3   222   56.9   54   116   480   0.44       NIC   PLUS       AVECOR   AFFINITY   2.5   235   57.5   54   100   270   0.48       TERUMO   CAPIOX SX   1.8   112   55.1   45   202   270   0.52       COBE   OPTIMA   1.7   131   56.9   47   187   260   0.56       BARD   HF 5700   3.7   304   57.9   57   187   560   0.48       SORIN   MONOLYTH   2.2   155   56.9   48   89   290   0.52       MACCHI   OXIM II-34   3.2   350   57.6   56   105   490   0.46           PLUS       MACCHI   OXIM II-34   2.2   212   58.1   57   167   530   0.46                  
 
         [0118]    From this chart it is readily apparent that the present adult oxygenator  150  provides a large advantage over the competition in one of the key aspects of a successful oxygenator, its priming volume. The low priming volume of 170 ml is nearly 100 ml less than the next smallest, and nearly 400 ml less than the largest in this group. In addition, the oxygenator  150  has the lowest effective aggregate hollow fiber surface area, and performs acceptably in all the other categories in comparison with the competition. The reduction in hollow fiber surface area translates into a lower cost for the oxygenator.  
         [0119]    Importantly, the oxygenator  150  has an O 2  transfer rate of about 57.5 ml/min/lpm at a blood flow rate of about 7 lpm. This means that the oxygenator  150  transfers a volume of oxygen that more than one third of its blood prime volume in one minute, at a flow rate of 7 lpm (which is typical for adult patients). The ratio of the oxygen transfer rate (at the prescribed flow rate) to prime volume is about 0.34 (57.5/170) lpm/min. The nearest competitor has such a ratio of only about 0.22 (56.9/260) lpm/min.  
         [0120]    A comparison chart similar to the one given above for the neonatal/infant oxygenator  450  is provided below.  
                                                                                   TABLE VI                           PERFORMANCE COMPARISON OF NEONATE/INFANT MEMBRANE OXYGENATORS                                        HOLLOW                               PRIME   FIBER                   MAXIMUM       PRESSURE   VOLUME   EFFEC-                   BLOOD   PRIME   DROP (mmHg)   (ml)   TIVE               PATIENT   FLOW   VOLUME   (at 1 lpm blood   (at 1 lpm   SURFACE       MFG   MODEL   WEIGHT   (lpm)   (ml)   flow)   blood flow)   AREA (m 2 )                    MACCHI   Present   Neonate/   2.0   60   27   0.75   1.0           Invention   Infant       BENTLEY   Baby Spiral   Infant   2.0   115    4   0.78   N/A       MEDTRONIC   Minimax   Infant   1.5   140   62   0.6   0.6       DIDECO   Liliput   Neonate   0.8   60   45   0.82   0.34                           (at 0.8 lpm   (at 0.8 lpm                           blood flow)   blood flow)       DIDECO   702   Infant   2.5   150   40   0.72   0.62       TERUMO   Capiox 308   Neonate   0.8   80   75   0.82   0.8                           (at 0.8 lpm   (at 0.8 lpm                           blood flow)   blood flow)       POLYSTAN   Safe Micro   Neonate   0.8   52    0.87   0.87   0.33                           (at 0.8 lpm   (at 0.8 lpm                           blood flow)   blood flow)                  
 
         [0121]    Again, the priming volume of the neonatal/infant oxygenator 450 is the lowest in its class, along with the Dideco Liliput, which also has a priming volume of 60 ml. The Dideco oxygenator, however, has a maximum blood flow of only 0.8 lpm, and is thus only suitable for use with neonatal patients. In contrast, the present oxygenator  450  has a blood flow of up to 2.0 lpm, and is a suitable for use with both neonatal and infant patients. Importantly, the oxygenator  450  has an O 2  transfer rate of about 62.5 ml/min/lpm at a blood flow rate of about 2 lpm. This means that the oxygenator  450  transfers a volume of oxygen of the same magnitude as its blood prime volume in one minute, at a flow rate of 2 lpm (which is typical for infant patients). The ratio of the oxygen transfer rate (at the prescribed flow rate) to prime volume is about 1.04 lpm/min. Furthermore, the neonatal/infant oxygenator  450  is comparable in all other categories, although it has a slightly larger hollow fiber effective surface area, and thus requires more fibers, which is a small price to pay for the reduction in prime volume.  
         [0122]    Heat Exchanger Advantages  
         [0123]    In addition to providing a low prime volume oxygenator, the present invention realizes several advantages by moving the heat exchange function from the oxygenator to the reservoir. First, the heat exchanger is highly efficient.  
         [0124]    Tables V and VI also illustrate the performance factor of the present heat exchanger positioned in the reservoir in comparison to the performance factor of the heat exchangers in prior art heat exchangers. The performance factor is a measure of the temperature change of the respective fluids passing through the heat exchanger (here, typically blood and water), and is calculated as follows:  
           P.F. =( T   b,out   −T   b,in )/( T   w,in   −T   b,in )  
         [0125]    where:  
         [0126]    T b,in =Inlet temperature of the blood  
         [0127]    T b,out =Outlet temperature of the blood  
         [0128]    T w,in =Inlet temperature of the water  
         [0129]    As can be seen, the performance factor of the heat exchanger of the present invention is comparable to those of the prior art. This results from the specific arrangement of the heat exchanger within the reservoir. Although there have been reservoirs in the prior art incorporating heat exchange coils, they have been what may be termed flooded chamber reservoirs with relatively inefficient heat exchange capacities. With flooded chamber reservoirs, the performance of the heat exchanger is a function of the blood level therein. The present heat exchange/reservoirs shown and described above utilize a separate heat exchange chamber within the reservoir chamber to provide a single pass of blood across the heat exchange coils. That is, blood enters the reservoir chamber at an upper end and is guided through the annular heat exchange chamber and across all of the coils. Therefore, heat transfer takes place in a fairly confined region and a maximum volume of blood is in and around the heat exchange coils at all times, so that the heat transfer therebetween is made more efficient. Perhaps more importantly, the performance of the heat exchanger is not a function of the blood level in the reservoir.  
         [0130]    One disadvantage from locating the heat exchanger in the oxygenation chamber, in a so-called closed system, is that the blood is submitted to certain additional stress. By locating the heat exchanger in the reservoir, as in the present invention, mechanical stress on the blood is reduced. That is, the blood passes through the heat exchanger by gravity (or under a slight vacuum) in a natural drainage progression rather than being forced past heat exchange tubes or fins with a fluid pressure generated by a pump. Of course, the blood exiting the reservoir is then impelled through the oxygenator and back to the patient using a pump, but the separation of the heat exchange and pressure elevation stages in the extracorporeal system helps reduce damage to the blood. In other words, the blood is not subjected to mechanical stresses within the heat exchange chamber.  
         [0131]    Finally, the arrangement of the heat exchanger within the reservoir further reduces the prime volume of the entire extracorporeal circuit. In contrast to flooded chamber reservoirs, blood enters the reservoir chamber at an upper end and falls by gravity through the annular heat exchange chamber and across the coils before being filtered and flowing into the lower portion of reservoir chamber. Thus, previously unused volume within the reservoir chamber is now utilized by the heat exchanger.  
         [0132]    It is understood that the examples and embodiments described herein and shown in the drawings represent only the presently preferred embodiments of the invention, and are not intended to exhaustively describe in detail all possible embodiments in which the invention may take physical form. Indeed, various modifications and additions may be made to such embodiments without departing from the spirit and scope of the invention.