Junction for shear sensitive biological fluid paths

A biological fluid transport device comprises a cutwater at the junction of at least two blood flow paths. The cutwater is substantially straight, substantially vertical, or both. At least one of the fluid paths may be tubular, and in some embodiments all of the fluid paths are tubular. The shear sensitive fluid may be, without limitation, blood, blood-based combinations, cell culture media, cell suspensions, proteins, and microcapsule suspensions. The device may be part of an extracorporeal circuit (e.g., blood during heart-lung bypass procedures or blood processing), but it need not be. Preferred embodiments of the device include, without limitation, kinetic pumps, mass transfer devices, filters, reservoirs, and heat exchangers.

BACKGROUND 
Shear sensitive fluids, including biological fluids such as blood and 
blood-based combinations, should not be exposed to sudden or extreme 
changes in pressure or temperature, impacts, vibration, or rapid changes 
in direction of flow. Nonturbulent flow is the preferred mode of handling 
shear sensitive fluids. 
DISCLOSURE OF THE INVENTION 
The invention is a biological fluid transport device comprising a cutwater 
at the junction of at least two fluid paths or circuits, the cutwater 
being substantially straight, or substantially vertical, or both. The 
junction is the location where a fluid path is split into two or more 
paths. For example, the junction can be an outlet for fluid to leave a 
device or an inlet for fluid to enter a device. At least one of the fluid 
paths or circuits may be tubular, and in some embodiments all of the fluid 
paths or circuits are tubular. The shear sensitive fluid may be, without 
limitation, blood, blood-based combinations such as "platelet gel," cell 
culture media, cell suspensions, proteins, and microcapsule suspensions. 
The device may be part of an extracorporeal bypass circuit but it need not 
be. Preferred embodiments of the device include, without limitation, 
kinetic pumps, mass transfer devices, filters, reservoirs, heat 
exchangers, and blood processing systems (such as diagnostic hemostasis 
management systems and blood coagulation testing systems).

DETAILED DESCRIPTION 
Many biological fluids are shear sensitive. Examples include blood, 
blood-based combinations, cell culture media, cell suspensions, proteins, 
and microcapsule suspensions. Any feature, or other obstruction present in 
the fluid flow path or circuit, can induce high shear by creating a high 
gradient, that is, a large change in velocity over a small area. (A fluid 
path is any series of locations occupied by the fluid. A circuit is a path 
which forms at least a portion of a closed loop, such as would be 
established with a path from a source of fluid to a device, and another 
path from the device back to the source. Of course, multiple devices could 
be employed.) 
Practical applications nearly always require that some or all of the fluid 
change direction so that it can be processed. Thus, most fluid transport 
devices comprise housings and other components which present junctions at 
which the fluid may flow in more than one direction. Similarly, such 
devices may comprise obstructions, interfaces, edges, and the like, 
somewhere along the path or circuit traveled by the fluid. Between such 
devices, junctions in fluid tubing and tubing-based accessories may also 
create undesirable shear stress in the fluids they carry. Examples of such 
junctions are in-line splitters and connectors which have more than one 
connection upstream and/or downstream of the flow path through the device; 
"Y" adapters and "T" adapters; manifolds, and the like. 
For example, in extracorporeal bypass circuits, a bodily fluid is removed 
from the body, presented to special purpose components, and returned to 
the body. A common extracorporeal circuit includes devices such as kinetic 
pumps, mass transfer devices, filters, reservoirs, and heat exchangers. 
(Some of these components may be incorporated into the design of other of 
the components. For example, a mass transfer device may have an integral 
heat exchanger, reservoir, filter, or a combination of any or all of 
them.) In the case of an extracorporeal blood circuit suitable for 
heart-lung bypass surgery and/or blood processing systems and diagnostic 
hemostasis management systems, the components may include bubble and 
membrane oxygenators, arterial filters, cardiotomy reservoirs, bubble 
separators, blood heat exchangers, and red blood cell washers. Other types 
of blood management systems employ extracorporeal blood circuits. The 
invention is suitable for all of these devices, both when they are 
incorporated into an extracorporeal bypass circuit, and when such devices 
are used for biological shear sensitive fluids outside the context of 
extracorporeal bypass (e.g., blood in coagulation testing systems, cell 
culture media, cell suspensions, proteins, and microcapsule suspensions). 
FIG. 1 is a cross sectional schematic view of a common feature in a generic 
device 10 which, for purposes of illustration only, is generally circular 
in cross section and has a housing 11 of negligible thickness. The device 
includes an outlet 12 that permits some or all of the fluid (not shown) to 
leave the housing when the fluid is traveling in the general direction 
indicated by flow arrows 14a-14d. The outlet 12 is commonly tubular (for 
reasons not critical to the invention) and called a "tangential outlet" 
since the axis of symmetry 16--16 of the outlet 12 does not generally 
coincide with a diameter 18--18 of the generally circular housing parallel 
to the flow through the tubular path 12. 
Although not shown in FIG. 1, the tangential outlet 12 need not be located 
so that the flow path axis 16 is exactly tangential with the generally 
circular cross-sectional profile of the housing. A relatively small amount 
of offset toward or away from the axis of symmetry 18 of the housing 11 is 
possible. Similarly, the outlet flow axis 16 and the housing diameter 18 
are commonly parallel in the cross-sectional plane, but slight deviations 
on the order of one to thirty degrees are possible. Finally, the outlet 
flow axis 16 and the housing diameter 18 are commonly coplanar in the 
cross-sectional plane, even if not exactly parallel in that plane, but 
slight deviations on the order of one to thirty degrees are also possible. 
In any of these three cases, or in any combination of two or three of the 
cases, minor modifications to the geometry of the invention may be 
preferred to produce an embodiment of the invention suitable for the 
particular device under consideration. In all such cases, the principles 
of the invention would still be employed and therefore all such 
embodiments are considered to be within the scope of the invention as it 
is explained below. 
Also, a common design technique is to introduce "draft," i.e., small 
deviations in various dimensions and/or angles, to provide adequate 
clearance for a molded housing to be removed from its mold. Such 
deviations are not necessarily reflected in the Figures or this 
description; however, incorporation of draft or other similar 
manufacturing techniques into a particular embodiment of the invention is 
preferred and not considered to be a departure from the scope of the 
invention. 
Generally speaking, fluid flows along the general direction of the flow 
paths 14a, 14b, 14c and 14d. Fluid then either enters the outlet 12 by 
following flow path 14e, or remains within device 10 by following flow 
path 14f. In detail, fluid flow in the vicinity of the junction of the 
generally circular main portion of the housing 11 and the outlet 12 will 
be drawn or split, and thus experience shear, at or in the immediate 
vicinity of the junction of the main housing 11 and the outlet 12. This 
junction comprises an edge commonly known as cutwater 20. The rate of 
change of fluid velocity at the cutwater 20 is a source of shear stress in 
kinetic pumps. 
FIG. 2A is a partial cross sectional view of the cutwater 20 showing 
together the straight and vertical edge characteristic of the invention, 
although the edge could be either straight or vertical. The vertical 
direction is substantially perpendicular to the primary direction of fluid 
flow at the cutwater location. The edge is designated "straight" or 
"vertical" to distinguish it from the conventional edge, indicated in 
phantom, which can appear straight and vertical when viewed directly in 
the plane of FIG. 1. The conventional edge is shown in phantom as the 
half-elliptical shape that follows naturally if outlet 12 is a right 
circular cylinder, as is conventional, and intersects circular housing 11 
along a generally tangential path. In the context of the invention, a 
"straight" cutwater or a "vertical" cutwater can have minor deviations 
from a perfectly straight and/or perfectly vertical linear edge, as long 
as those deviations are not significant on the scale of the vertical 
length (height) of the cutwater. For example, the cutwater could be 
straight or linear from end to end, but slanted slightly from vertical as 
shown in FIGS. 2B and 2C. FIGS. 2D through 2K show cutwaters which have 
minor curves at upper (FIGS. 2D and 2E) or lower (FIGS. 2F and 2G) points, 
or both (FIGS. 2H, 2I, 2J, and 2K). A slight curvature could be present 
over substantially all of the cutwater, as shown in FIGS. 2L and 2M. The 
cutwater could have more than one linear segment, as shown in FIGS. 2N and 
2O, with a slight angle between the segments. The apex of the angle need 
not be equidistant from the upper and lower points of the cutwater. 
Combinations of all of the above configurations are also possible. In all 
cases, the cutwater is considered to be substantially straight or 
substantially vertical or substantially straight and vertical, depending 
on the exact configuration chosen. 
Although the above description assumes that fluid within the device 10 
leaves the housing 11 through the outlet 12, the invention could also be 
practiced in a device in which the fluid direction was reversed. In such 
an embodiment, fluid would enter through a tangential inlet, pass a 
junction comprising a cutwater shaped as described above, and enter the 
device. Thus, in the broadest sense, the invention is a device for 
carrying biological shear sensitive fluids, comprising a straight or 
vertical cutwater at a junction of at least two fluid paths or circuits 
within the device. The junction is the location where the fluid flow 
within a fluid path is split into two or more other paths. 
Shear stress is the most significant contributor to hemolysis in blood 
pumps. FIGS. 3 and 4A to 4E illustrate an embodiment of the invention for 
use on an otherwise conventional centrifugal blood pump. In general, such 
a device comprises a housing 100 having an inlet (not shown) for fluid 
(not shown) entering the housing 100, and a tangential outlet 110 for the 
fluid to exit the housing 100. Within the housing 100, a rotating impeller 
increases the angular velocity of the fluid, but the impeller design 
preferably minimizes shear on the fluid. Once the fluid reaches the 
junction between the housing and the tangential outlet, it is exposed to 
the cutwater as described above. An example of such a pump is the BioPump 
model BP-80 commercially available from Medtronic Bio-Medicus of 
Minneapolis, Minn., USA. 
FIG. 4A shows a straight and vertical cutwater 120. FIG. 4B shows that the 
cross sectional profile of fluid outlet 110 is preferably rectangular 
(neglecting slight deviations due to draft) at a location common to the 
volume of the main portion of housing 100 and outlet 110. This cross 
sectional profile gradually tapers, as seen from the sequential cross 
sectional views of FIGS. 4C and 4D. FIG. 4E shows that the tapering does 
not continue to the end of the outlet where the fluid exits the pump; that 
is, the inner diameter of fluid outlet 110 is generally circular when 
viewed in cross section at fluid outlet 110. The tapering is a preferred 
embodiment that is not necessary to the practice of the invention. Also, 
the cross sectional area of the outlet 110 at the exit of the pump (FIG. 
4E) is preferably greater than the cross sectional area of the outlet 110 
at the junction with the main portion of the housing 100. This is to 
accommodate the inner diameter of tubing typically connected to the pump 
at the outlet, but it is not necessary to the practice of the invention. 
While cutwater 120 reduces shear stress due to its vertical and/or straight 
configuration alone, it is preferred to radius the edge. As shown in 
detail in FIG. 4F, cutwater 120 has a radius of curvature in the 
horizontal plane of preferably 0.001 to 0.030 inch, and most preferably at 
least 0.004 inch. The choice of radius of curvature should take into 
account the clearance between the cutwater and the impeller. 
The housing 100 may be constructed according to conventional techniques 
from a variety of materials approved for contact with biological fluids, 
such as medical grade polycarbonates suitable for blood and blood-based 
mixtures. A preferred material is available from the Bayer Corporation or 
the General Polymers Division of the Ashland Corporation under the Bayer 
tradename MAKROLON, specifically type RX-2530-1118 (see 
http://www.ashchem.com/GP/data/1373.htm). The surface finish on surfaces 
of the housing 100 which contact blood is preferably SPI/SPE No. 2. Rough 
surfaces, scratches, scuffs, nicks, cracks, etc. should be eliminated to 
reduce shear stress in the fluid. The inner surface can be coated with an 
antithrombogenic agent not essential to the invention. 
FIG. 5 shows a "2-way" connector 200 comprising a first fluid path 210 and 
second and third fluid paths 220 and 230. The first fluid path 210 can be 
an inlet to connector 200, with the second and third fluid paths 220 and 
230 being outlets. A substantially straight and/or vertical cutwater 240 
is shown in the cutaway portion at the junction of the three fluid paths 
circuits. Again, the conventional elliptical cutwater is shown in phantom. 
This could be an in-line flow connector for an otherwise conventional 
connection to suitable tubing, or it could be the configuration of an 
inlet or outlet on another otherwise conventional device (not shown), such 
as a mass transfer device (such as a bubble or membrane oxygenator), 
filters (such as an arterial or cardiotomy filter), reservoirs (such as a 
blood or cardiotomy reservoir), and heat exchangers. The embodiment of 
FIG. 5 is suitable for extracorporeal bypass circuit components, as well 
as components and circuits used for biological shear sensitive fluids 
outside the context of extracorporeal bypass (e.g., cell culture media, 
cell suspensions, proteins, and microcapsule suspensions). Application of 
the substantially straight or substantially vertical cutwater to "3-way" 
connectors, manifolds, and the like can easily be accomplished. 
The success of the invention is believed to be due to reduction of elevated 
shear forces in the vicinity of the cutwater created by a vortex set up by 
the flow over the cutwater surface. Fluid approaching a curved cutwater on 
the fluid outlet side follows a partially upward path as it crosses over 
the cutwater back to the main chamber of the device. This movement results 
in a mean rotational motion, that is, a vortex. Fluid upstream of the 
cutwater and on the bottom portion of the vortex, that would otherwise 
move to the main chamber of the device, is forced to move to the fluid 
outlet side of the cutwater in a turbulent motion. Turbulent motion is 
undesirable since it creates rapidly changing velocity components that 
induce shear stress on the fluid. The inventive cutwater induces less 
shear stress because it reduces rate of change of velocity components on 
either side of the cutwater. The conventional geometry induces higher 
shear by generating higher levels of vorti city as compared to the 
invention. Vorticity is generated as the fluid passes the cutwater. These 
vortices create substantial changes in the magnitude and direction of the 
fluid (i.e. change in velocity components) over a given area. The 
inventive geometry reduces induced rotational forces on the fluid and 
consequently reduces the compression of the fluid path. 
EXAMPLES 
Blood trauma caused by centrifugal pumps was measured for two sets of pumps 
which varied only in the cutwater configuration in a conventional 
tangential outlet. The configuration illustrated in FIGS. 2 through 4 
above was compared to a control group, that is, a comparative example 
which differed only in the design of the cutwater. The comparative example 
had a cutwater identical to that of a standard commercial-grade 
centrifugal blood pump designated Model Number BP80, available from 
Medtronic Bio-Medicus, Inc. of Minneapolis, Minn., USA. 
The in-vitro hemolysis test measured blood trauma caused by the 
extracorporeal centrifugal pumps. Plasma free hemoglobin levels are 
measured and reported over a four hour test duration. Free hemoglobin 
generation rate (mg/dl/hour) is calculated. Hematocrit is adjusted at the 
start of the test and monitored throughout the four hour test duration. 
The test requires 1000 cc of fresh bovine blood less than eight hours old. 
The blood is preferably washed and resuspended in saline, but this is not 
required. The blood plasma had an initial plasma free hemoglobin level 
less than 25 mg/dl. The blood did not "auto" hemolyze. The following test 
conditions were applied: 
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Blood Flow Rate 4 liters/min .+-. 5% 
Differential Pressure (P.sub.out - P.sub.in) 
400 mm Hg .+-. 20 mmHg 
Temperature 37 C. .+-. 1 C. 
Blood Volume 1000 cc .+-. 100 cc 
Hematocrit 30% .+-. 1% 
adjusted with saline solution 
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The maximum plasma free hemoglobin increase of the control from the 
baseline sample should be 10 mg/dl (milligrams per deciliter). If the 
negative control does not meet this criteria, the test for the device 
hemolysis is rendered invalid. Each device is tested over four hours, 
flowing at 4 l/minute. 
Plasma free hemoglobin (mg/dL) is measured at time 0 and at 60 minute 
intervals. Hematocrit is measured at time 0. Hematocrit is typically not 
expected to change substantially in these in-vitro tests. Flow 
(Liters/min), temperature, and pressure are measured throughout the test. 
The test requires a kinetic pump, a pressure monitoring device, a flow 
probe, a temperature monitoring device, a microhematocrit centrifuge, a 
blood bank centrifuge, a sequence of pressure reducers, a spectral 
photometer, sodium chloride 0.9%, sterile, for adjusting hematocrit and 
anticoagulant. The design, number, and location of the pressure reducers 
are selected to minimize introduction of additional hemolysis. For 
example, a series of four inline reducers in the pump outlet line is 
preferred. 
The fluid handling circuit is a closed system, including the kinetic pump, 
a blood reservoir bag, 4 to 5 feet of PVC tubing (3/8 inch I.D.) and 
plastic connectors. Hematocrit of the blood is adjusted to 30% by adding 
saline. Blood samples are drawn for blood trauma analysis according to the 
sampling plan. 
The absolute rate of hemolysis was measured for 48 samples of a kinetic 
pump using a housing having the configuration of FIGS. 3-4. The absolute 
hemolysis rates are listed in the second column of Table 1. The third 
column of Table 1 shows the ratio of the hemolysis rates of the pumps of 
FIGS. 3-4 to the comparative example, pumps having the cutwater identical 
to that of the commercially available BP-80 pump as described earlier. 
Entries of 1.00 indicate no change in hemolysis rate, with entries less 
than 1.00 indicating improvement and entries greater than 1.00 indicating 
degradation in performance. Sample number 1 was omitted from the data 
analysis. 
As indicated in the mean (N=47) hemolysis ratios, the improved cutwater 
design resulted in a 22% decrease in rate of hemolysis. As shown in FIG. 
6, the decrease in hemolysis was present in the vast majority of cases 
over a range of absolute hemolysis rates from approximately 3 to 20. 
TABLE 1 
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Sample Absolute Rate 
Hemolysis 
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1 93.19* 3.53* 
2 26.48 1.00 
3 47.65 1.81 
4 20.37 0.77 
5 7.339 0.76 
6 6.164 0.64 
7 6.645 0.69 
8 8.578 0.89 
9 13.103 0.87 
10 11.519 0.76 
11 10.374 0.69 
12 13.188 0.87 
13 5.346 0.81 
14 11.487 1.75 
15 4.074 0.62 
16 4.042 0.62 
17 4.264 0.45 
18 7.171 0.75 
19 3.507 0.37 
20 3.698 0.39 
21 26.45 0.99 
22 21.704 0.81 
23 20.895 0.78 
24 18.657 0.70 
25 11.329 0.69 
26 12.936 0.79 
27 12.022 0.73 
28 8.789 0.54 
29 11.729 0.60 
30 10.081 0.51 
31 12.497 0.64 
32 19.783 1.01 
33 12.286 1.45 
34 5.271 0.62 
35 6.783 0.80 
36 4.367 0.52 
37 8.99 0.66 
38 8.044 0.59 
39 9.757 0.71 
40 8.244 0.60 
41 13.042 0.66 
42 11.088 0.56 
43 15.33 0.78 
44 13.891 0.71 
45 14.289 0.78 
46 14.784 0.81 
47 20.306 1.11 
48 15.699 0.86 
Count 47 47 
Mean 12.43 0.78 
Std. Deviation 7.84 0.28 
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*indicates data not used to calculate mean and standard deviation