A flow-through centrifuge free of rotating seals. The centrifuge includes a frame having three spaced apart horizontal plates which carry a central bowl, a countershaft and a tube-supporting hollow shaft. A motor is arranged to drive the frame at an angular velocity of .omega.. The countershaft is driven by a stationary pulley on the motor and drives the bowl at an angular velocity of 2.omega.. The motion of the countershaft is also transferred to the tube-supporting hollow shaft by a pulley coupling having a ratio which effects rotation of the hollow shaft, with respect to the frame, at an angular velocity of -.omega..

FIELD OF THE INVENTION 
This invention relates to flow-through centrifuges free of rotating seals. 
The present invention relates, more particularly, to flow-through 
centrifuges which provide continuous transfer of material into and out 
from a centrifuge bowl via tubes which are directly connected to the bowl 
from outside of the centrifuge without the use of rotating seals. 
BACKGROUND OF THE INVENTION 
Conventional flow-through centrifuges utilize rotating seals which can 
become a source of leaks between the inflow and the outflow lines. The 
rotating seals represent a weak point in the machinery in terms of the 
performance life time, complexity and fragility of its parts and the 
necessity for a continuous and comparable degree of lubrication, all 
shortcomings of prior art centrifuges of flow-through type. These 
shortcomings are distinct disadvantages no matter what materials are to be 
centrifuged on a flow-through basis. 
When these continuous-flow centrifuges are adapted for an on-line blood 
separation, as applied to the collection of blood cells, rotating seals 
become critical in terms of platelet injury, red cell hemolysis, and 
obstruction of the channels by aggregates and impaired lubrication of the 
rotating seals. 
SUMMARY OF THE INVENTION 
It is an object of the present invention to provide a flow-through 
centrifuge which does not require any rotating seals. 
It is another object of the present invention to provide a flow-through 
centrifuge which avoids the possibility of leaks between inflow and 
outflow lines. 
It is a further object of the present invention to provide a flow-through 
centrifuge which has a long performance life time. 
It is an additional object of the present invention to provide a 
flow-through centrifuge which is both simple and robust. 
It is yet another object to provide a flow-through centrifuge which can be 
used for on-line blood separation without injury to platelets and without 
red cell hemolysis. 
The foregoing objects, as well as others which are to become clear from the 
text below, are achieved in accordance with the present invention by 
providing a flow-through centrifuge which includes a centrifuge bowl 
operatively arranged to rotate about a central axis at an angular velocity 
of 2.omega.. A bundle of tubes, constituting at least one inflow line and 
at least one outflow line, is connected at one end to the bowl and is 
tightly supported at its other end. The bundle of tubes is formed in a 
partial loop radially displaced from the central axis. The partial loop is 
operatively arranged to rotate about the central axis at an angular 
velocity of .omega.. The bundle of tubes remains free of twisting by being 
counterrotated about its own axis at -.omega..

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
As illustrated in FIGS. 1 and 2, an illustrative embodiment of a 
flow-through centrifuge according to the present invention, includes a 
frame composed of three spaced-apart, horizontal, circular plates 10-12. 
Each of the plates 10-12 is provided with a plurality of apertures which 
extend through the plate near its periphery. Corresponding apertures in 
each of the plates 10-12 are axially aligned with one another. A plurality 
of tubular spacers 13 are positioned between the plates 10 and 11 and a 
further plurality of tubular spacers 14 are positioned between the plates 
11 and 12 in alignment with the aforementioned apertures, only two of the 
tubular spacers 13 and two of the tubular spacers 14 being visible in FIG. 
1. Bolts 15 extend through the respective axially aligned apertures in the 
plates 10-12 and the corresponding tubular spacers 13 and 14, each bolt 15 
being held in place by a corresponding respective nut 16. The rigidly 
connected plates 10-12 are driven by a motor shaft 17 which is fixed to 
the center of the lowest plate 12 by conventional means, shown as a wing 
nut 18. A stationary toothed pulley 19 is mounted on the motor housing 20, 
the stationary pulley 19 being connected, via a toothed belt 21 to a 
toothed pulley 22 which is fixed to the lower end of a countershaft 23. 
The countershaft 23 extends through apertures in the plates 10-12 within 
which respective ball bearings 24-26 have been fixedly positioned. A gear 
27 is fixedly connected to the upper end of the countershaft 23 and a 
toothed pulley 28 is fixedly connected to the countershaft 23 between the 
plates 10 and 11. 
As shown to the left in FIG. 1, a rigid, hollow shaft 29 is positioned 
within further apertures provided in the respective plates 10 and 11 and 
operatively positioned so as to be rotatable in respective ball bearings 
30 and 31 which are respectively fixed in these additional apertures in 
the respective plates 10 and 11. A toothed pulley 32 is fixedly connected 
to the hollow shaft 29 and coupled to the pulley 28 via a toothed belt 33. 
A hollow shaft 34 extends through centrally positioned apertures in the 
plates 10 and 11, this hollow shaft 34 being positioned for rotation 
within ball bearings 35 and 36 which are carried respectively in the 
central apertures of the respective plates 10 and 11, a spherical bearing 
37 being provided for supporting the lower end of the hollow shaft 34. A 
gear 38 is fixed to the hollow shaft 34 and meshed with the gear 27, the 
gears 38 and 27 having a 1:1 ratio. The upper end of the hollow shaft 34 
is threaded to receive a ring nut 39. 
As illustrated in FIGS. 1 and 2, a centrifuge bowl 40 according to the 
first embodiment of the present invention, includes a base member 41, 
preferably constructed of aluminum. The base member 41 has a central 
aperture through which the hollow shaft 34 extends, and is clamped between 
the ring nut 39 and a flange 42 which extends radially outward from the 
hollow shaft 34 above the gear 38. A donut-shaped, transparent silicon 
rubber bag 43 is positioned fixedly within a recess formed in the upper 
surface of the base member 41. The base member 41 is provided with a first 
shoulder 44 which extends radially outward from and adjacent to the recess 
within which the silicon rubber bag 43 is positioned. The base member 41 
has a second shoulder 45 which extends radially inward and adjacent to the 
recess within which the silicon rubber bag 43 is positioned. A flat, 
centrally apertured, transparent, plastic lid 46, which can be 
advantageously made of lucite, is positioned over the recess in the base 
member 41. The lid 46 is held in position by a first plurality of bolts 
47a and a second plurality of bolts 47b which extend through the 
transparent plastic lid 46 and respectively into the base member 41 
beneath the respective shoulders 44 and 45, although each of the bolts 
47a, 47b could extend through the base member 41 and be held by an 
associated nut. As illustrated, the transparent lid 46 is provided with 
three bores 48-50 positioned at different radial distances from the axis 
of rotation of the drive shaft 17. The bores 48-50 are in fluid 
communication with the interior of the silicon rubber bag 43, via 
respective apertures therein. As visible in FIG. 2, the bores 48-50 
terminate not in the flat upper surface of the transparent lid 46, but 
rather extend through respective nipple-like protuberances 51-53 which 
project upwardly in the otherwise flat upper surface of the transparent 
lid 46. 
A bundle 54 consisting of three flexible tubes 55, 56 and 57 is fixed 
within an opening which is coaxial with the drive shaft 17 and may be 
formed, for example, in a cover 58 associated with the housing of the 
centrifuge. The bundle 54 of tubes 55-57 extends radially outward from the 
axis of rotation of the drive shaft 17 to the hollow shaft 29, downwardly 
through the hollow shaft 29, radially inwardly from beneath the hollow 
shaft 34 and upwardly through the hollow shaft 34 so that each of the 
tubes 55-57 is positioned above the transparent lid 46. The flexible tube 
55 is positioned over the nipple-like protrusion 51 on the surface of the 
lid 46 and communicates with the interior of the silicon rubber bag 43, 
via the bore 48 for the purpose of feeding blood into the bag 43. The free 
ends of the respective flexible tubes 57 and 56 are positioned 
respectively over the nipple-like protrusions 52 and 53 formed in the 
surface of the lid 46 so as to communicate with the interior of the 
silicon rubber bag 43, via respective bores 49 and 50, at different radial 
distances from the axis of rotation of the centrifuge as defined by the 
axis of rotation of the drive slaft 17. As illustrated, whole blood may be 
fed into the silicon rubber bag 43 via the flexible tube 55, flexible 
tubes 56 and 57 providing conduits for removing respectively plasma and 
red cells from the interior of the silicon rubber bag 43. It is to be 
appreciated that suitable pumps (not shown) may be provided for feeding 
blood into the flexible tube 55 and for pumping blood components from the 
flexible tubes 56 and 57. 
A counterweight 59 is provided beneath the plate 12, it being held in place 
by a bolt 60 and an associated nut 61. The counterweight 59 is positioned 
radially opposite to the pulley 22 and the countershaft 23 so as to 
balance the frame. 
It is to be appreciated that the silicon rubber bag 43 may be equipped with 
three internal flow lines, in lieu of its illustrated fluid communication 
with the bores 48-50, these internal flow lines communicating with the 
flexible tubes 55-57 either through the transparent lid 46 or other 
apertured portions of the bowl 40. 
In operation, the drive shaft 17 of the drive motor drives the frame, 
including the horizontal plates 10-12, at a particular selected angular 
velocity .omega., for example at 1000 r.p.m. The toothed pulley 22, which 
is fixed to the countershaft 23, rotates about the axis of rotation of the 
drive shaft 17 and, because of its connection, via the toothed belt 21, to 
the toothed pulley 19 fixed to the housing of the drive motor, causes the 
countershaft 23 to rotate within the bowl bearings 24-26. As a result of 
this movement of the countershaft 23, the gear 27 drives the gear 38 at an 
angular velocity of 2.omega. because of the 1:1 gear ratio. As a result, 
the bowl 40, which like the gear 38 is fixed connected to the hollow shaft 
34, rotates at an angular velocity of 2.omega.. 
At the same time, the toothed pulley 28, rotating with the countershaft 23, 
drives the toothed belt 33 which, in turn, drives the toothed pulley 32 
fixed to the hollow shaft 29. This causes the hollow shaft 29 to rotate 
about its own axis at an angular velocity of -.omega.. As a consequence of 
this, the bundle 54 of the flexible tubes 55-57 does not become twisted 
and yet allows fluid communication into and out from the transparent 
silicon rubber bag 43, without the presence of any rotating seals, When 
properly balanced, the flow-through centrifuge bowl can be operated at 
speeds up to 2,000 r.p.m. for the purpose of separating blood components 
and at even higher speeds for other purposes. 
In order to demonstrate the capacility of a flow-through centrifuge 
according to the invention, heparinized (1.5 mg/kg) sheep blood was 
introduced into the centrifuge directly from the animal (weight 34 kg) 
while effluents of plasma and red blood cells were returned (after 
sampling) to the animal. The flow rates through the individual lines were 
controlled by two roller pumps, one set on the whole blood line and the 
other on the plasma return line, the third line having a flow equal to the 
difference between the two pumps. With a constant feed rate of 60 ml/min, 
plasma free of red blood cells was harvested at 12 ml/min at 1000 rev/min 
or 18 ml/min at 1300 rev/min. During 12 hours of continuous flow of plasma 
at 18 ml/min, blood and plasma samples were collected at intervals so that 
changes in the platelet counts could be studied. The results shows a 50% 
reduction in the blood platelet count within the first hour, and a 
reduction to 30% of the base line values by the twelfth hour of operation 
without any evidence of red blood cell hemolysis. 
It is to be appreciated that the centrifuge bowl 40 (FIGS. 1 and 2) may be 
replaced or modified, depending on the particular centrifuging task at 
hand, without departing from the present invention. 
In the event it is desired to prove a flow-through centrifuge for effecting 
continuous density gradient cell separation, it is only necessary to 
remove the transparent, plastic lid 46 and the transparent, silicon rubber 
bag 43 from the centrifuge bowl 40 shown in FIGS. 1 and 2. A thin 
polytetrofluoroethylene sheet 62 is positioned in the bottom of the recess 
in the base member 41 from which the silicon rubber bag 43 was removed. An 
outer silicon rubber O-ring 63 or a similar sealing washer, which may be 
made of silicon rubber or the like, is positioned on top of the sheet 62 
adjacent the shoulder 44 for the purpose of sealing the outer periphery of 
the chamber in which cell separation is to be carried out in the thus 
modified centrifuge bowl designated generally by the numeral 64. An inner 
silicon rubber O-ring 65 or a similar sealing washer is positioned on top 
of the sheet 62 adjacent the shoulder 45 to provide for sealing of the 
inner periphery of the chamber in which the cell separation is to be 
carried out. A septum 66 (FIG. 3) made of silicon rubber or the like 
extends radially outwardly between the inner O-ring 65 and the outer 
O-ring 63 to provide for radial separation within the chamber in which 
cell separation is to take place. 
A transparent, plastic lid 67, which may be of lucite, of special 
construction is positioned on the shoulders 44 and 45, defining between 
its lower surface and the thin sheet 62 a centrifuge chamber. The lid 67 
is held in position by the bolts 47a and 47b as in the embodiment 
illustrated in FIGS. 1 and 2. 
Six inlet bores 68 are provided through the lid 67 on that side of the 
septum 66 which is in the direction of rotation of the centrifuge bowl 64. 
Six outlet bores 69 are provided through the lid 67 on the other side of 
the septum 66, as can best be seed in FIG. 3. The bores 68 and 69 allow 
fluid communication with the centrifuge chamber defined in the space 
between the inner surface of the transparent lid 67 and the sheet 62. Each 
of the inlet bores 68 terminate, not in the flat upper surface of the lid 
67, but extend through nipple-like protrusions 70 which are particularly 
adapted to receiving the free ends of flexible tubes which are not unlike 
the tubes 55-57 shown in FIG. 1. Similarly, each of the outlet bores 69 
extend through nipple-like protrusions 71 which upstand from the upper 
surface of the lid 67. 
As illustrated, the six inlet bores 68 are displaced radially from the axis 
of rotation of the centrifuge bowl 64, which is determined by the axis of 
rotation of the drive shaft 17 at differing distance, the distance between 
adjacent ones of the inlet bores 68 being substantially identical. 
Similarly, the six outlet bores 69 are positioned at different radial 
distances from the axis of rotation of the centrifuge bowl 64, adjacent 
ones of the outlet bores 69 being substantially equidistant from one 
another. The outlet bores 69 as a group are positioned at greater radial 
distances than the corresponding inlet bores 68, each outlet bore 69 being 
positioned further radially outward from the axis of rotation of the bowl 
64 than its corresponding one of the inlet bores 68. 
Each of the inlet bores 68 and each of the outlet bores 69 is to be placed 
in fluid communication with a respective one of a total of twelve 
flexible, flow tubes (not illustrated) which are bundled, protected by a 
tubing preferably filled with silicon grease and led to the outside of the 
centrifuge via the hollow shaft 34 and the hollow shaft 29 in the same 
manner as the tubes 55-57, illustrated in FIG. 1. 
The six inlet feed tubes, in operation, continuously introduce liquids of 
different density increasing in order from inner to the outer positions of 
the inlet bores 68, thus creating a density gradient inside the centrifuge 
bowl 64 within the chamber defined between the inner surface of the lid 67 
and the thin sheet 62. Cells suspended in the liquid fed from the 
innermost hole travel in a spiral path acting under the centrifugal force 
field resulting in the separation of the cells according to density. The 
thusly separated cells are continuously eluded through the outlet bores 69 
into six fractions. It is to be appreciated, of course, that any number of 
fractions could be realized, depending principally on the number of inlet 
and outlet bores and associated tubes provided. It is also to be 
understood that while cell separation has been particularly mentioned 
above, the particular centrifuge bowl 64 illustrated in FIGS. 3 and 4 
could be used to provide separation of materials other than cells into 
various fractions according to density. 
In the event it is desired to adapt the centrifuge of FIG. 1 for use in 
separating a mobile phase from a stationary phase of a two-phase solvent 
system or to adapt it to a single system in which particles are to be 
subjected to eluderation using a single solvent system, it is only 
necessary to remove the transparent plastic lid 46 and the silicon rubber 
bag 43 as first steps in providing a modified centrifuge bowl denominated 
generally by the numeral 72 in FIGS. 5 and 6. A long helix of narrow-bore 
tubing 73 having two free ends is positioned within the recess defined in 
the base member 41 adjacent the shoulder 44. Although not necessary, the 
narrow bore tubing 73 is desirably positioned about a ring 74 of circular 
cross section, the ring 74 being positioned within the recess in the base 
member 41 in the vicinity of shoulder 44. Although only one loop of the 
helically wound narrow-bore tubing 73 is illustrated in FIGS. 5 and 6, it 
is to be understood that several loops may be made about the recess within 
the base member 41. A transparent, plastic lid 75, which may be of lucite, 
is positioned on the shoulders 44 and 45 of the base member 41. As 
illustrated, the two ends of the tubing 73 are placed in fluid 
communication with respective bores 76 and 77 which extend through the lid 
75 in the vicinity of its outer circumference. The bores 76 and 77 
terminate at their upper end not at the flat surface of the lid 75 but, 
rather the bores 76 and 77 extend through nipple-like protrusions 78 and 
79 which extend upwardly from the flat surface of the lid 75, which 
nipple-like protrusions 78 and 79 allow a flexible inlet tube and a 
flexible outlet tube to be placed in fluid communication respectively with 
the bores 76 and 77. Such inlet and outlet tubes (not shown) correspond to 
the tube 55 and the tube 57 shown in FIG. 1. The free ends of the 
helically wound narrow-bore tubing 74 are placed in fluid communication 
with the respective bores 76 and 77 with the aid of nipple-like 
protrusions on the underside surface of the lid 75, these protrusions 
being constructed similarly to the nipple-like protrusions 76 and 79. It 
is to be understood that in some applications, the free ends of the 
narrow-bore tubing could extend upwardly through somewhat enlarged 
openings positioned as are the bores 76 and 77 in the lid 75 and be placed 
in communication with respective inlet and outlet tubes. As in the case of 
the other embodiments, the inlet and outlet tubes are threaded downwardly 
through the hollow shaft 34, outwardly to the hollow shaft 29, inwardly to 
the opening in the fixed member 58 and thence respectively to a supply and 
to a member which is to receive material eluted through the helix of 
narrow-bore tubing 73. 
Under proper centrifugal force fields, each turn of the helix of 
narrow-bore tubing 73 retains the stationary phase of a two-phase solvent 
system, while the mobile phase continuously elutes through it. Thus, a 
sample solution containing solutes or particles is subjected to a 
partition process between the two phases and is finally eluted through the 
outlet tube. In the event a single solvent system is established, 
particles are subjected to elutriation in each coil of the helix and 
separated according to size and density under the influence of a 
centrifugal force field. 
It is to be appreciated that flow-through centrifuges made in accordance 
with the present invention have broad application. Such centrifuges may be 
applied to plasmopheresis, cell washing and elutriation, zonal 
centrifugation, and counter-current chromotography, to specifically 
mention a few of the applications. 
The foregoing description and accompanying figures of drawings relate to 
illustrative embodiments of flow-through centrifuges constructed in 
accordance with the present invention. These illustrative embodiments have 
been set out by way of example, not by way of limitation. Other 
embodiments and numerous variants are possible within the spirit and scope 
of the present invention, its scope being defined by the appended claims.