Centrifuge with movable mandrel

There is disclosed herein a liquid processing apparatus for use in centrifugal apheresis in which whole blood is received from a donor, separated into therapeutic components and selectively collected. The apparatus includes a processing chamber support system for cooperating in controlling the volume of a variable-volume blood processing chamber during apheresis. The support system is constructed to spin about a spin axis and is substantially symmetric about said axis. The elements of the support system include a chamber cover for receiving a variable-volume chamber. A mandrel is provided for engaging the variable-volume chamber and applying a conforming force to the chamber by urging the chamber toward the cover and thereby causing the chamber to conform to the shape of the cover. Thus the chamber is positioned between the cover and mandrel during apheresis, and the cover and mandrel cooperate in controlling the volume and shape of the chamber. The apparatus and chamber define an annular blood volume having a blood sedimentation surface and a cylindrical plasma volume having a cylindrical blood/plasma interface. The area of the blood sedimentation surface is greater than the interface area so as to maximize blood cell separation while minimizing platelet separation during the red blood cell separation and collection.

BACKGROUND OF THE INVENTION 
This invention relates to a centrifugal liquid processing apparatus, and 
more particularly, to an improved apparatus for centrifugal apheresis, 
such as plasmapheresis or plateletapheresis. 
In recent years the separation of whole blood into therapeutic components, 
such as red blood cells, platelets and plasma, and collection of those 
components has increased significantly. The separation is generally 
achieved in a centrifuge and is referred to as centrifugal apheresis. 
In centrifugal processing, whole blood is delivered to a processing chamber 
where the blood is centrifugally separated into therapeutic components. 
The processing chamber is commonly bowl-shaped, rigid and disposable. 
Presently whole blood is taken from a donor at a donation site and is then 
transported in a sterile container to a central processing laboratory 
where it is processed for separation and collection of the therapeutic 
components. 
The apparatus used at the processing laboratory for centrifugal apheresis 
is bulky, expensive and usually not conducive for use at the donation 
site. However, on-site processing is becoming more popular since the time, 
handling and storage between donation and processing can be minimized. 
Furthermore, therapeutic component yield can be increased if processing 
for separation and collection is performed during donation. For example, 
in on-site processing greater quantities of platelets can be collected 
because greater quantities of whole blood can be processed for platelets 
and returned to the donor. Since the volume of blood being processed may 
vary and the chamber volume may vary during component separation and 
processing, the processing bowls and the apparatus which cooperates with 
the bowls must be capable of handling the varying volumes. 
In U.S. patent application, Ser. No. 560,946 filed on even date herewith 
and entitled "Flexible Disposable Centrifuge Chamber", there is disclosed 
a flexible, variable-volume, bowl-shaped chamber which can be used in 
on-site processing apparatus. 
It is the object of this invention to provide an apparatus for on-site 
centrifugal apheresis which is constructed for use in systems where the 
volume of biological fluids processed is variable. 
It is another object of this invention to provide an apparatus for on-site 
apheresis which is convenient to use and of a lower cost to manufacture. 
These and other objects of this invention will become apparent from the 
following description and appended claims. 
SUMMARY OF THE INVENTION 
There is provided by this invention a centrifugal liquid processing 
apparatus for use in the onsite processing of whole blood into therapeutic 
constituents by centrifugal apheresis (e.g., plasmapheresis or 
plateletpheresis). The apparatus is particularly useful with a flexible, 
variable-volume, processing chamber and includes a chamber bowl or cover 
for receiving the processing chamber. A chamber-engaging mandrel is 
provided for engaging said chamber and causing the chamber to conform to 
the cover and for cooperation in controlling the volume of said chamber. 
The cover and mandrel are spun about a spin axis and the processing 
chamber spins therewith for separating the components. Fluid conduits are 
provided for connecting the chamber to the donor and to external sites for 
the collection of the therapeutic components. 
The mandrel, cover and chamber cooperate to define a blood-collecting 
volume generally along the side walls of the chamber and a central plasma 
collecting volume at the base of the chamber. These volumes are 
substantially equal and remain equal as the total chamber volume changes. 
Furthermore, the chamber is configured so that the surface area at which 
red blood cells will separate is greater than the surface area of the red 
blood cell/plasma interface. The result of the volume and surface area 
relationships is to maximize red blood cell (RBC) separation while 
minimizing platelet sedimentation back into the red blood cell bed or 
packed cell bed during RBC separation and collection.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
The System in General 
Referring now to FIG. 1, an apparatus for centrifugal apheresis 10 
generally is shown and includes a rotatable external assembly or housing 
12 and a rotatable inner chamber support assembly 14 which carries the 
variable-volume chamber and movable mandrel. 
The housing 12 is generally cylindrical in shape and includes top and 
bottom half sections 16 and 18 which are connected by hinge 20. The bottom 
section 18 is connected to a drive system 22, which spins the outer 
housing at a first predetermined speed about a spin axis A--A. Different 
types of drive systems are known in the art and can be employed. See U.S. 
Pat. Nos. 3,986,442 Khoja et al and Re. 29,738 Adams for exemplary drive 
systems. 
The top section 16 carries the inner chamber support assembly 14, which is 
positioned within the outer housing 12 and aligned with the spin axis A--A 
for rotation with the outer housing 12. An inner assembly drive 23 is 
mounted to the top section 16 and supports the chamber and cooperating 
members via drive shaft 24. The inner assembly drive spins the inner 
assembly 14 in the same direction as the outer assembly 12, but at twice 
the rate. 
If the rate of rotation for the outer housing is designated as one-omega 
(i.e., 1.omega.), then the rate of rotation for the inner assembly is 
two-omega (2.omega.) in the same direction. Use of the 1.omega./2.omega. 
drive permits the entire apparatus to be connected to the stationary 
external blood sources and collection sites using conduits or stationary 
seals (i.e., non-rotating seals). 
Systems which employ such drives and fluid connections are disclosed in the 
previously identified patents as well as U.S. Pat. Nos. 4,108,353 Brown; 
4,109,852 Brown et al; and 4,109,855 Brown et al. Furthermore, mechanical 
and electrical control systems are known for maintaining the 
1.omega./2.omega. drive relationship. A control system designated by block 
diagram 26 is connected to both drives 22 and 23. 
The inner assembly includes an inverted cup-shaped chamber support plate 
28, which carries the chamber bowl or cover 30 and spring-biased chamber 
mandrel 32. A flexible, variable-volume, bowl-shaped chamber is positioned 
in the cover between the cover and mandrel, as best seen in FIGS. 2-4. A 
fluid conduit, which is sometimes referred to as an umbilicus 34, extends 
from the cover through the outer housing to a stationary external 
connection 36. The umbilicus can be either a single or multi-lumen tube. 
See, for example, U.S. Pat. Nos. 4,132,349Khoja et al and 4,389,207 
Bacehowski et al. 
The cover 30 is fixed to the chamber support plate 28 by a removable band 
38 which releasably secures the cover to the support plate. 
Both the outer and inner housings are substantially symmetric about the 
central spin axis A--A, and during operation, the chamber conforms to the 
shape of the mandrel and cover and assumes a generally axially symmetric 
shape. 
Mounting of the Chamber 
Referring to FIG. 2, the processing chamber, which is a flexible, 
variable-volume, bowl-shaped member 40, is shown with a fluid 
communication port 42. This port is to be located on the spin axis A--A 
and is referred to as the low-gravity (low-G) port. In some systems a port 
is also located at the radially outermost point and is referred to as the 
high-G port. In a distended shape the chamber has a bladder-like shape 
that can be formed to the bowl-like shape. 
In order to mount the chamber to the support assembly, the top section 16 
of the outer housing is swung open about hinge 20 to an inverted 
horizontal position, the retainer band 38 is removed, and the chamber bowl 
cover is removed as shown in FIG. 2. Thereafter, a flexible, 
variable-volume chamber 40 is fitted to the mandrel 32 by rolling the 
chamber thereon. This chamber 40 has been fabricated from two heat-sealed 
and vacuum-formed polyvinylchloride sheets. The sealing flange 44 is shown 
engaging the support plate 28. 
In a sense, the chamber is fitted to the mandrel as a glove is fitted to a 
hand. In this inverted position the mandrel is extended under a biasing 
action, but its movement is limited by the drive shaft. After the chamber 
is fitted to the mandrel, the bowl cover 30 is refitted and secured with 
the retainer band and the top section is returned to its closed position. 
The Internal Assembly 
FIG. 3 shows the fully assembled inner assembly with the variable-volume 
chamber in place. More specifically, the internal drive 23 is supported by 
the outer housing top section 16. The drive shaft 24 is aligned with the 
spin axis A--A and extends downwardly from the drive 23 through the 
support plate 28. 
The drive shaft 24 includes a support plate connecting pin 24a for 
establishing a driving connection with the support plate 28. 
The support plate 28 includes a transverse top wall 28a which has a 
downwardly-extending bosslike stub 28b. The stub includes an aperture 28c 
through which the drive shaft 24 extends and defines a spring seat 28d. A 
drive pin connecting groove 28e is provided on the drive side of the stub 
28b for driving connection with the pin 24a. The support plate also 
includes a peripheral side wall 28f that terminates in an 
outwardly-extending flange 28g. The flange 28g may include one-half of a 
high-G port opening 28h. 
The bowl cover 30, which is secured to the support plate 28, includes a 
transverse bottom wall portion 30a, and an upwardly-extending and 
outwardly-tapering side wall portion 30b which terminates in flange 30c 
that cooperates with the support plate flange 28g for securing the bowl 30 
to the plate 28. 
A conduit-receiving aperture 30d extends through the bottom wall, is 
aligned with the spin axis A--A and the low-G port 42 passes therethrough. 
The flange also includes a high-G port opening 30e which can be aligned 
with port opening 28h to form a high-G outlet. The cover 30 has a slot 30f 
which extends through the side wall from the flange to the port. 
The mandrel 32 is positioned inside the cover 30, is shaped to generally 
conform to the interior of the rotor and has a bottom wall 32a, tapering 
side wall 32b and skirt 32c. The bottom wall is provided with a retainer 
recess 32d. 
A spring-biasing mechanism is provided for urging the mandrel 32 toward the 
bowl 30 and against the chamber 40. The biasing mechanism includes a 
coiled compression spring 46 that surrounds the drive shaft 24, and is 
held in position at the top end by the stub 28b and spring seat 28d and at 
the bottom end by post-like keeper 48. 
The post 48 is an elongated, hollow, cylindrically-shaped member which 
seats in the mandrel recess 32d. The post includes a body portion 48a 
which fits within the spring 46 and an outwardly-extending flange or 
spring seat 48b on which the lower end of the spring rests. At the upper 
end, the post 48 has a top wall 48c with an aperture 48d through which the 
drive shaft 24 extends. 
The drive shaft has at its lower end a retainer groove 24b which is 
positioned within the post 48 and a C-shaped retainer spring 24c which 
fits within the groove to retain the post 48 on the drive shaft and limits 
the extension of the spring 46. 
Thus the biasing spring cooperates with the support plate stub 28b, post 
48, drive shaft 24, pin 24a, and retainer 24c to urge the mandrel against 
the processing chamber 40 and toward the bowl 30. The maximum extension of 
the spring is controlled by the length of the drive shaft, between the pin 
24a and retainer 24c, positioning of the retainer 24c, as shown in FIG. 2, 
mandrel engages the bowl 30 as shown in FIG. 3. The limit for compression 
of the spring 46 is defined by its solid height; abutment of the post 48 
and the stub 28b; and/or engagement of the mandrel skirt 32d and support 
plate. 
After assembly and installation of the chamber and closure of the housing, 
the biasing spring 46 urges the post 48 and, thus the mandrel, downwardly 
toward the bowl cover. The downward travel of the mandrel is limited by 
the restraint of the bowl and the engagement of the shaft retainer 24c and 
post 48. In the fully extended position, the mandrel expresses 
substantially all fluid from the chamber, and, as shown, the chamber is 
prepared for receiving whole blood and component separation. 
In operation the centrifuge is started with drives 22 and 23, and whole 
blood drawn from the donor is delivered to the chamber via the umbilicus 
34. The whole blood entering the chamber causes the chamber to expand and 
push against the mandrel 32. As the chamber fills, it conforms to the 
shape of the mandrel and cover and urges the mandrel toward a retracted 
position. As the mandrel retracts, the post 48 is pushed upwardly, which 
causes the spring 46 to compress until the chamber is fully expanded or 
until the spring reaches its fully compressed solid height where the post 
abuts the support plate stub. 
During separation, therapeutic components may be selectively withdrawn from 
the chamber through the low-G port 42 (or other ports if provided), thus 
decreasing the chamber volume. As the chamber volume decreases, the 
mandrel advances toward the cover, thus maintaining a conforming force 
against the chamber. As the mandrel advances and retracts in response to 
volume changes, the rim edge 40a of the chamber rolls up and down. 
The chamber is sufficiently flexible so as to permit adjustment in volume 
without fracturing or tearing. It will be noted that the chamber walls may 
fold back against themselves during this process. At the end of the 
procedure, the chamber is removed by opening the housing and interior 
casing and then sliding the chamber off the mandrel. 
From the foregoing it will be seen that the apparatus disclosed herein 
provides an apparatus for centrifugal apheresis in which the volume of the 
processing chamber is variable. 
The RBC and Plasma Volumes 
The shape of the bowl 30 and mandrel 32 cooperates with the chamber 40 to 
define a red blood cell collection volume and a plasma collection volume. 
Referring to FIG. 4, the plasma collection volume 50 is a cylindrical, 
disc-like space between the bowl bottom wall 30a and the mandrel bottom 
wall 32a. The blood cell collection volume is the annularly-shaped space 
52 defined by the bowl side wall 30b and the mandrel side wall 32b. 
The blood cell collection volume 52 and plasma collection volume 50 are 
approximately equal as shown in the filled condition in FIG. 4. 
Furthermore, the volumes remain approximately equal to each other as the 
total volume of the chamber varies. In other words, throughout the range 
of chamber volumes from empty to full, the ratio of red blood cell or 
packed cell collection volume to plasma collection volume remains 
substantially constant at about 1:1. 
Referring now to the packed cell collection volume 52, it is seen that 
during operation the red blood cells sediment toward or are driven toward 
the bowl wall 30b. This wall has a large surface area so as to maximize 
separation of the red blood cells. 
The interface between the packed or red blood cell volume and plasma volume 
is a cylindrically-shaped surface, shown with dotted lines, which extends 
between the outer edge of the mandrel bottom wall 32a and the outer edge 
of the cover bottom wall 30a. During separation, a layer known as the 
"buffy layer" forms at that interface due to the separation of the 
platelets from the plasma. As shown, the interface surface area is smaller 
than the RBC sedimentation surface. The reason the interface surface area 
is smaller is to minimize platelet separation during RBC collection. 
In the embodiment shown herein, the RBC sedimentation surface area is 
greater than the platelet interface surface area. Desirably, the ratio of 
RBC surface area to interface surface area is at least 2:1 and even as 
great as 4:1. These relationships are selected so as to maximize RBC 
separation while minimizing platelet from plasma separation and loss into 
the buffy layer during RBC separation. During RBC separation fluids in the 
red blood cell volume 52 are exposed to high-G forces, while fluids in the 
plasma volume 50 are exposed to low-G forces. 
In operation, the chamber is filled with whole blood and then subjected to 
a first or hard spin to obtain RBC separation. During this spin, red blood 
cells sediment and move radially outwardly and into the volume 52 where 
the cells then sediment toward the outer wall. During this operation 
plasma and platelets are displaced inwardly toward the plasma volume 50. 
Platelet-rich plasma collects in the volume 50 and is subjected to much 
lower G or separation forces since its radial distance from the spin axis 
is less than that for the RBC's. Hence platelet separation from the plasma 
is minimized. 
In one example, the chamber is filled with about 500 milliliters of whole 
blood having a hematocrit of 40 (i.e., 40 volume percent red blood cells). 
After spinning and separation, about 250 milliliters of packed red blood 
cells, with a hematocrit of 80, is obtained in the volume 52 and about 250 
milliliters of platelet-rich plasma is available in the plasma volume 50. 
Collection of the RBC or platelet-rich plasma can be effected through the 
high or low-G ports as desired. Thereafter, in subsequent separations 
platelets can be separated from the plasma so as to permit separate 
collection of platelets and plateletfree plasma. 
It will be appreciated that numerous changes and modifications can be made 
to the embodiment shown herein without departing from the spirit and scope 
of this invention.