CA1261765A - Method and apparatus for separation of matter from suspension - Google Patents

Abstract

Abstract of the Disclosure A system for filtration of matter from a liquid suspension through a membrane uses a rotor within a concentric shell rotating with a surface velocity which, together with the rotor-shell gap and suspension viscosity, establishes vigorous vortex cells about the rotor. At least one of the rotor and shell surfaces include a filter membrane. Tangential velocity components at the membrane surface constantly sweep the membrane surface to limit cell deposition tendencies while constantly replenishing the medium to be filtered. The vortex cells are established along the length of the membrane despite the constant extraction of filtrate and the resultant change in physical characteristics of the suspension.

Description

12~765 METHOD AND APPARATUS FOR
SEPARATION OF MATTER FROM SUSPENSION
Back~round of the Invention ; This invention relates to membrane filtration of matter from liguid suspensions, and particularly to biomedical applications of such technology. It is especially relevant to, but not limited to, the separation or fractionation of the constituents of blood.
Techniques for the separation and collection of ;given constituents of whole blood are in wide use for many therapeutic, medical and experimental applications. Plasma-pheresis (the separation of fluid plasma from the red and white cells of whole blood) forms the basis of widespread plasma storage and supply systems, and also is employed in-creasingly in therapeutic apheresis. Plasma is collected from individual donors by withdrawing whole bLood, separating the plasma, and preferably returning high hematocrit (high cell percentage) ~ractions back to the donor. Plasmapheresis by centrifugal separation is widely used in laboratories but ;is essentially a batch process of limited convenience and commercial practicality. Continuous centrifugal separation is desired if plasma is to be collected rapidly and with minimum donor inconvenience, and in the modern state of the art this cannot be done at reasonable cost. Blood handling and collection systems must be completely sterile, which in effect requires that all elements in contact with the blood be low cost disposable components or devices. Many workers in the art have thus experimented with membrane filtration techniques, in which a membrane with suitably small pore size (e.g. 0.5 microns) is utilized to filter plasma from the blood. Because of the viscous and complex quality of whole ~. , 12~765

2 66119-21 blood, simple filtratlon does not suffice hecause deposition ~clogging of pores with cellular matter) qulckly decreases the efflciency of transfer through the membrane.
Recogniz1ng these problems, a number of workers in the art have sought to utilize the shear principle so as to increase efficiency. Transport of whole blood laterally across a membrane sur~ace which is moving relative to an opposed surface sets up shearing forces on ~he blood shee~, tending to keep the cellular matter in motion and to lift it away from the membrane pores, substantially reducing the deposition problem.
Workers in the art have ohserved a generally increaslng relationship between the amount of shear and the e~ficiency o~
the filtration process, with an upper limlt being imposed by unwanted cell disruption or hemolysis, typically at maximum shear rates of 7,500 to lO,OOO~sec with prior devices.
Membrane filtration effectively appeared to have reached a practical limit with various flat membrane configurations, because of various pressure losses and flow discontinuities. In practice, a ~ubstantial membrane area has been required for such configurations, in order to enable plasma collection at a reasonable rate from an individual donor. However the membrane cost is high and the system efficiency decreases with the duration of usage. Thus the desirable objectlve of a low cost disposable has not been heretofore achieved with a reliably operating system.
More re~ently, however, a remarkable advance in blood separation technology using membrane fil~ration has arisen from a different structure, described in United States patent application Serial No. 449,470, filed December 13, 1982, by Halbert Ftschel and havlng a common assignee. The confi~uration described in that patent application provldes filtration rates in excess of ten ti~es ~hat found in prior .~

~26~ i5

3 6~119-21 membrane filtration devlces, for a given surface area. A
membrane covered splnner, having an interior collection system, is disposed within a stationary shell, and blood is fed into the space between the spinner and the shell, moving both circumferentially about the shell and along the longitudinal axi~ to a spaced apart exit region. A practical devlce, having a gap of .030" and a rotational velocity of approxima~ely 3600 r.p.rn., with a spinner dlameter of 1" (2.54 cm) and length of 3" (7.5 cm) enables plasma to be derived at approximately 45 mltmin, and with hi~h plasma recovery (e.g. in excess of 70%).
A plasma recovery of 0.9 ml~c~ /min is achieved ln contrast to prior art fla~ plate systems providing about 0.039 ml/cm /min and hollow fiher systems providing 0.013 ml/cm /min. The slgnlficant improvement in filtration efficiency thus afforde~
makes a low cost plasmapherasis disposable practical for ~he first ti~e, and enables two to three units of blood ~o be transferred conveniently and quickly as high hematocrit remainder is returned to the donor.
Whlle flow conditions existing between a rotating spinner and a concentric shell have been much studied, ~eing termecl Couette flow, the extraction of a filtrate through a membrane on the spinner represents a s~ecial case of potentially wide applicability. Generically, thls configuration encompasses a number of systems in which a fllter member spinning withln a bath is used to prevent or limit particulates in the bath rom adherin~ ~o the fllter, while drawing filtrate into the interior of the spinner. Particular examples of these are shown in an article by M. Lopez-Leiva entltled "Ultrafiltration at Low Degrees of Con~entration Polarization, Technical Possibilities" in Desallnation (Netherlands) Vol. 35, pp. 125-128 ~1930) dealing w~th the concentra~ion of milk produc~s, and ln United States Patent No.

765i ~ 66119~21

4,184,952 (Shall Oil) dealing with the extractlon of oil from basic sedlmen~ and water. However, ~here is nothing in these disclosuxes that would tend to indicate that the signlficant improvement achieved by Fischel in plasmapheresis would even be possible, or explain the mechanism of separation in such a sys~em. The Fischel patent application as filed hypothesized ~hat a "shear centrifugation" effect takes place, with centrifugal forces acting to cause migration of the cellular matter outwardly toward the statlonary wall, while a plasma-rich layer resides at the surface. Limiting factors on theperformance of this system were described in terms of conditions to maintain laminar flow between the spinner and the outer wall, while also exerting suf~icient centri~ugal force to achieve outward cell migration. Thus the application purported to dis~inguish from other rotating flow systems in which relative movement between two concentric cylinders causes creation of localized cellular structures, called Taylor vortices, between the walls.
Taylor vortlces also have been intensively investigated in the literature and a number of devices, particularly oxygenators proposed by Brumfield, in United States Patent Nos. 3,771,658, 3,771,899 and g,212,241, have been considered that utilize such effects. Mos~ of the investigations of Taylor vorticas are concerned with theoretical aspects, and few systems, including the ; oxygenators, have been successfully implemented using these ~ principles. No syætems using Taylor vortices are known in - which the dynamics o~ the ~luid medium between the members are affected or altered by continuous extraction of constituents from the medium.
The situation in which a filtrate is extracted from a complex fragile living system, such as whole blood, can be seen ~26g~7~5 the membrane pores as filtrate is rapidly extracted.
According to a broad aspect of the invention there is provided a system for filtering plasma matter capable of passing a membrane from a fluid suspension, comprising: a housing body having a hollow interior and an inner surface substantially concentric with a central axis and including a plurality of surface yrooves; rotor means rotatable within the housing body, the ro~or means having a smooth outer surface concentrate with the inner surface of the housing body and spaced apart therefrom and further including magnetic means interior to the housing body; means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body; filter membrane means disposed on the inner surface of the housing body for passing the plasma to : the surface grooves in the housing body; conduit means in tbe housing body in communication with the surface grooves in the filter membrane means for collecting flltrate pa~sing therethrough; and means magnetlcally coupled to the magnetic means o~ the rotor means for driving the rotor means at a rate selected relative to the tangential veloci~y of the rotor means, the space between the rotor means and the housing body and the physical characteristics of the fluid suspension to establish annular vortices ahout the rotor means substantially filling the space between the rotor means and the housing body.
According to another broad aspect of the invention there is provlded a system for filtering plasm~ capable of passing a membrane from a blood suspension, comprising: a housing body having a hollow interior and an inner surface sub~
stantially concentric with a central axis; rotor means rotatable within the housing body, the rotor means having an outer surface concentric with the inner surface of the housiny 5a 126:~L765 6611g-21 body and spaoed apart therefrom; means ~or feediny the fluid suspension into the space between the rotor means and the inner surface of ~he housing body; filter membrane means disposed on the inner surface of the housing body and comprising a membrane having a smooth surface with deviations less than a predetermined pore size selected to pass the plasma; conduit means in the housing body in communication with the outer surface of the filter membrane means for collecting filtrate passlng therethrough; means coup~ed to the rotor means for driving the rotor means at a rate selected relative to the tangentlal velocity of the rotor means, the space between the rotor means and the housing body and the physlcal characteristics of the blood suspension to astablish annular vortices about the rotor means substantially filling the space between the rotor means and the housing body; means ~or sensiny the transmembrane pressure; controllable means for withdrawing unfiltered suspension fed between the rotor means and the :~ housing body; and means responsive to the sensed transmembrane pressure for increasing the rate of withdrawing unfiltered suspension to enable internal cleaning of the filter membrane means by action of the annular vortices.
Accordlng to another broad aspect of the invention there is provided a blood constituent filtering system comprising: a sta~ionary housing having an inner wall portion;
a rotatable spinner disposed within the housing and having an :~ outer wall portion disposed opposite said ~nner wall and defining a gap area therebe~ween capable of sustaining Coue~te flow having Taylor vortices within the gap area; a filter membrane disposed on at least one of said wall portions and sized to fil~er out plasma while bein~ cons~antly swept across by cellular blood constituen~s entrained in said Taylor vortices and thus tending to dislodge from the membrane any 5b ~26~765 cellular blood constituents, a fluid inlet to said yap area and thus to a first side of said filter membrane for passing blood constituents thereinto; a fluid outlet from said gap area passing concentrated cellular blood constituents therefrom; a filtrate outlet communicating with the other side of said filter membrane for passing plasma; means for monitoring the transmembrane fluid pressure across said filter membrane during system operation; and means for temporarily increasing the fluid flow passing through said fluid ou~let from the gap area in response to transmembrane fluid pressure in excess of almost 165 mm Hg and thus causing a temporary reduction in filtrate flow rate through the membrane and enhanced sweeping of the filter membrane by cellular blood constituents and thus an enhanced self-cleaning membrane action.
According to another broad aspect of the invention there is provided the method of fil~ering a cellular suspension passing between a rotating spinner and an outer shell without clogging a filter membrane on one of the sur~aces comprising the steps of: establishlng a plurality of annular vortices in the suspension about the spinner and ad~acent the membrane;
sensing the transmembrane pressure while maintaining a desired extraction rate of filtrate through the membrane; compariny the transmembrane pressure to a transmembrane pressure value calculated to achieve extraction of filtrate with desired membrane efficiency and without substantial dama~e to the cellular components; and reducing the extraction rate of filtrate while maintaining the vortex action to clean the membrane when the transmembrane pressure rises above the : calculated value.
According to another broad aspect of the invention there is provided a system or filtering a cellular suspension ~1 ., .~

~Z~6~
66119-~1 passing between a rotating spinner and an outer shell without clogging a filter membrane on one of the surfaces comprising2 means for establishing a plurality of annular vortices in the suspension about the spinner and adjacent the membrane; means ; for sens.ing the transmembrane pressure while malntaininy a desired extraction rate of filtrate through the mem~rane; means for comparing the transmembrane pressure to a transmembrane pressure value calculated to achieve extraction of filtrate with desired membrane efficiency and without substantial damage to cellular components; and means for reducing the extraction rate of filtrate while maintaining the vortex action to clean the membrane when the transmembrane pressure rises above the calculated value.
According to another broad aspect of the invention there is provided a system for filtering a cellular suspension, comprising: a housing body having a hollow interior and an lnner surface including a plurality of surface grooves; rotor means rotatable within the housing body, the rotor means having an outer surface spaced from the inner surface of the housing bocly; means for feeding the fluid suspenslon into the space between the rotor means and the inner surface of the housing body; filter membrane means disposed on the inner surface of the housing body for passing the plasma to the surface grooves in the housing body; conduit means in the housing body in communication with the surface grooves in the housing body for collecting filtrate passing therethrough; and means magnetically coupled to the rotor means for driviny the rotor means at a rate selected to establish annular vortices about the rotor means substantially filling the space between the rotor means and the housing body.

5d 'J ;l ~%6~765 66~19-21 Accordiny to anokher broad aspect of the invention there is provided a system for filtering a cellular suspension, comprising: a housing body havin~ a hollow interior and an inner surface including a plurality of surface grooves; rotor means rotatable within the housing body, the rotor means having an outer surface spaced from the inner surface of the housing body; means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body; filter membrane means disposed on the inner surface of the housing body for passing the flltrate to the surface grooves in the housing body; conduit means in the housing body in communication with the surface ~rooves in the housing body for collecting filtrate passing therethrough; and means on said housing body for accessing the inner surface thereof and means for releasably attaching the filter membrane means thereto.
According to another broad aspect of the invention there is provided a -~ystem for filtering a cellular æuspension, comprisingz a housing body having a hollow interior and an inner surface; rotor means rotatable within the housing body, the rotor means having an outer surface space from the inner surface of the housing body; mean~ for feeding the cellular suspension into the space between the rotor means and the inner surface of the housing body; filter membrane means on at leas~
one of the inner sur~ace of the housing body and the outer surface of the rotor means; conduit means in communica~ion with the filter membrane means for collecting filtrate passing the~ethrough; means for driving the rotor means at a rate selected to establish annular vortices wlthin the space between the rotor means and the housing body substantially filllng the space between the rotor means and the housing body; means for 5e ~Z6~76S ~

sensing the transmembrane pressure; controllable means for ; maint~aining a desired filtrate extrackion rate through the membrane means; and means responsive to the sensed transmembrane pressure for reducing the extraction rate of filtrate while maintaining the vortex action when the transmembrane pressure rises above a calculated value to clean the filter membrane means by action of the annular vortices.
According to another broad aspect of the invention there is provlded a blood constituent filtering system of the type which, in operation, produces Taylor vortices within a gap area disposed between relatively rota~ing generally cylindrical surfaces, at least one o~ which includes a blood constituent filtering membrane to filter out a blood constituent and for ; passing a filtrate therethrough, said system including: first means for detecting the onset of filter membrane pore clogging by cellular blood constituents; and second means for controlling at least one operating parameter of the filtering system to cause cleaning of the clogged pores by the sweeplng action of blood constituents entrained in sald Taylor vor~ices and passing adjacent said filtering membranes.
According to another broad aspect of the invention there is provided a blood constituent filtering ~ethod of the type which produces Taylor vortices within a gap area disposed between relatively ro~ating surfaces, a~ least one of which includes a blood cons~ituent filtering membrane to filter out plasma and for passing the plasma therethrough, said method including: detecting the onset of filler membrane pore clo~ging by cellular hlood constituents; and controlling at least one operating parameter of the filtering system to cause cleaning of the clogged pores by the sweeping ac~ion of blood constituents entrained in said Taylor vortices and passing

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adjacent said filtering membrane.
Accord.ing to another broad aspect of the invention there is provided a blood constituent filtering method comprising: relatively rotating two surfaces spaced apart to define a longitudinally extending gap area along which a flow of blood constituents havlng Taylor vortices is passed, with the Taylor number being in the range of about 75 to about 250;
providing on the outer one of said cylindrical sur~aces a blood constituent filtering membrane to filter out a blood constituen~ while being continually swept by blood constituents entrained in said Taylor vortices and passing a filtrate through said membrane; passing blood constituents into said gap area at a ~irst location and extracting concentrated cellular blood constituents from said gap area at a downstream longitudinally spaced apart location; and extracting the filtrate passing through said filtering membrane.
According to another broad aspect of the invention there is provided a system for filtering plasma from blood wlth a disposable unitr comprising: a disposable housing body includlng a rotor ~herein, at least one of the housing and rotor having a membrane filter thereon with a pore size in the range o~ 0.1 to 1.0 mi~rons, and plasma conduits therein for conducting plasma to a plasma outlet, the rotor including magnetic means therein, the housing body being spaced apart from the rotor to define an annular gap and including blood ; inlet means leading into the annular gap, spaced apart cell :~ concentrate outlet means communi~ating with the annular gap~
: and plasma outlet means communicating with the plasma conduits;
magnetic drive means exterior to the housing body and magnetically coupling to the magnetic means in the rotor for rotating the rotor at a rotational velocity selected, relative 5g F

~6~5 to the diameter of the rotor and the annular gap to establish a Taylor number of 70 to 250 throughout the annular gap with a shear rate below 12,000/sec; means coupled to the blood inlet means for feeding blood into the annular gap at a predetermined rate; pressure sensor means communlcatlng with the annular gap for sensing the transmembrane pressure of the blood in the annular gap; means responsive to the transmembrane pressure for comparing the transmembrane pressure to a threshold pressure de~ermined primarlly by the pressures requlred to overcome centrifugal forces, system pressure drop~ and plasma flux across the membrane, and generating a responslve control slgnal ~`~ when the transmembrane pressure exceeds the comparison; and means responsive to the control slgnal for varying at least one flow rate in the system apart from the predetermined inlet rate to malntain the Taylor numbex in the range of 70 to 250 whlle : reduclng the tendency of blood cells to clog the membrane.
According to another broad aspect oi the lnventlon there is provided the method of ~ilterlng about two to three units of plasma from whole blood using a rotary member : 20 posltioned with a predetermined gap with a disposable houslng, at least one of the rotary member and housing having a membrane filter surface and conduit means leading to a plasma outlet in the housing, comprising the steps of: feedlng blood into the gap between the rotor and housing at a predetermined rate;
rotatlng the rotary member wlthin the housing at a rate selected relative to ro~ary member size, gap width and blood vlscosity to establish Taylor vortices in the blood and cell concentrations through ~ha length of the rotary member;
extracting plasma from the plasma outlet at the desired rate in steady state operation by controlling the rate of cell con~entrate removal; sensing the ~ransmembrane pressure of :`
5h.

. .

. . : . .

~;~61765 ~

~lood in the gap as a measure of inltiation of deposition of cellular matter on the membrane filter surfaces; comparing the sensed transmembrane pressure to a threshold pressure sufficient to overcome forces needed for pumping plasma through the membrane but less than 165 mm Hg; generating a control signal when the sensed transmembrane pressure exceeds the thresholds; lowering the rate of plasma extraction while main~aining the Taylor vortices to ef~ect cleaning of deposited cellular matter from the membrane filter surface; and returning to steady state operation after the transmembrane pressure has been recluced.
Systems and methods in accordance with the invention are particularly useful in overcoming the many and difflcult problems of hemapheresis systems, but are equall~ well suited for a wide range of other applications. The concept appears use~ul wherever the aggregate viscosity of the system permits es~ablishment of strong Taylor vorkices over a length of spinner despite constant filtrate extraction, and the density of solid or particulate matter within the suspension allows entrainment of the matter within the circulating vortices.
In a specific example of a filtra~ion system and method, a vortex action is created khat is well above the onset of Taylor cells but below levels at which destructive shear might occur. A membrane covered spinner having an internal filtrate collection system is separated from a concentric outer wall by a predetermined radial gap within which an augmented :
~ but substantially uniform vortex action is , 5i : , , :1;261~

maintained despite filtrate extraction. Preferably the radial gap is selected to be near the upper end o~ the permissible range where shear and vortex forces are maximum with the other factors being adjusted accordingly. This insures that the velocity of extraction through the membrane, which tends to draw cells into the membrane, is more than counteracted by the orthogonal velocity components sweeping the membrane sur-face. The vortex action is not so vigorous that inward flow causes cell deposition on~the membrane or outward flow causes ; lO excessive turbulence and destructive effects. The coun-ter-rotating vortices constantly mi~ the matter in suspension, replenishing the supply of potential filtrate available at the membrane surface, adjacent each vortex cell. ~oreover there is substantially constant advance of the cells from input to output, so that local static conditions cannot exist.
Filtrate within the suspension is more mobile than the entrain-ed cellular matter or solids and can be interchanged between vortex cells so as to tend to equalize filtrate extraction rates throughout the membrane.
Under conditions of strong but controlled vortex circulation, the tangential flow velocitiescan advantageously be balanced for specific purposes against radial ~low velocity through the membrane for. In a plasma~heresis system, for example, the transmembrane pressure and the plasma throughput ("~ take") are readily determined by instrumentation devices and real time calculations. The transmembrane pressure rela-tive to plasma throughput for a 100% efficient membrane is ~; derived by analysis or empirical observation, to establish a reference identifying the onset of cell deposition. When the transmembrane pressure increases to or above the level at which cell deposition is imminent, separation systems in accordance with the invention reduce the filtrate throughput rate at least for a time. The consequent decrease in filtrate radial flow velocity allows the tangential flow components to free deposited cells or maintain efficiency, thus clearing the membrane and restoring system efficiency. No known filtra-tion systems have this internal capability.

7~5 ... .. . .. . ....... . . . .. . .

Another feature of systems in accordance with the invention is that the surface topology of the membrane is selected relative to the nature of the suspension being fil-tered. To enhance the vortex ac-tion and minimize occlusion of membrane by blood, for example, a smooth surfaced membrane is employed that has surface irregularities no greater than the pore size. Despite the fact that membrane surface varia-tions may be minute in many commercial membranes, they nonethe-less can hemolyze and entrap red cells while diminishing the local surface effects of vortex action. Thus superior results are achieved by employing smooth surfaced membranes under these conditions.
- Other systems in accordance with the invention im-plant the ~ilter membrane in the outer, stationary, wall with a number of constructional advantages and minimal reduction in operating efficiency. The stationary membrane surEaces may readily be replaced for use of the system as a separator for dia~nostic applications, or for applications where the ; system is to be operated continuously for extended periods.
In a specific example of this type of separator, the vorte~
~; flow is established by a spinner retained within a concentricsplit housing that can be opened to replace longitudinal filter membranes. An external magnetic drive rotates the spinner at an angular velocity that insures, relative to the gap and suspension viscosity, that strong vortices exist to provide sweeping action and freedom from clogging àt the membrane. With a slightly lower extraction rate than used in an interior membrane system operating with a given spinner surface velocit~, a high % take i5 nonetheless achieved. The velocity or gap dimension can be increased to provide a higher % take in many instances. The system has further advantages if used for diagnostic or analytical purposes because the membrane can be replaced and the unit can repeatedly be reused ~` by rinsing the membrane between operations.
A specific example of a system for providing supe-; rior plasmapheresis operation employs maximized gap spacings ~ for a given rotational rate, together with Taylor numbers in ~2~i~7~5 the range of 70 to 250 and shear rates oE 7500/sec to 10000/sec maximum. Among the further aspects of the invention, pore sizes can be used that are in the range of 0.8 to 1.0 microns, these being larger and more efficient than those hereto~ore used. In addition, blood Elow through the separation device can be against gravity if desired for specific purposes.
Inasmuch as minimal membrane area is desired ~or low cost plasmapheresis disposals, a relatively small range of gap sizes and angular veLocities is employed for achieving maxi-mized and constant throughput rates for plasma. For example,with a 1" diameter rotor the gap dimension is held in the range between about O.nl8" and 0.030" for r~tor angular veloc-ities of 3000 to 3600 r.p.m.
` Brie-f Descrietion o the Drawings A better understanding of -the invention may be had by reference to the following description, taken in con-~unction with the accompanying drawings, in which:
Fig. 1 is a combined perspective view, partially broken away and block diagram of a plasmapheresis system in accordance with the invention;
Fig. 2 is an enlarged and simplified fragmentary perspective view of a part of the plasma separation device in the arrangement of Fig. 1, showing vortex flow character-tlCS;
Fig. 3 is an enlarged side sectional view of the arrangement of Fig. 2, depicting vortex flow as described in the literature and as seen in operation;
Fig. 4 is a graph showing changes in plasma delivery for given input flow, with changes in the relationship between gap and angular velocity for a given size spinner;
Fig. 5 is a graph showing plasma flux changes for different gap sizes, other factors remaining constant;
Fig. 6 is a perspective view, partially broken away, of a different example of a system in accordanc0 with the invention utilizing a stationary membrane;
Fig. 7 i5 a side sectional view of the system o~
Fig. 6; and ~6~765 Fig. 8 is a perspective view, somewhat idealized and not to scale, o-f a fragment of a filtratlon membrane, showing the surface irregularities in one type of membrane.
Detailed Description o~_the Invention ~ plasmapheresis system 10, referring now to Fig. 1, in which the elements have been depicted only generally, provides a particularly suitable example of a blood separation system in accordance with the invention. Whole blood is taken from a donor via a needle means 12, shown as a single needle 10although a double needle system mav alternatively be used.
Disposable tubing is utilized to conduct the blood from the donor, and to combine it with a flow of anticoagulant ~rom a source 13 (flow control ~or the anticoagulant being of any one of a number of known types and -therefore not shown). ~n input blood pump 14, such as a peristaltic or pressure roller device, feeds the combined flow, when actuated by an associated blood pump control 16, to a transmembrane pressure sensor 18 and also to a disposable plasma separator device 20. The plasma separator 20 is in the form of a spinner 22 having 20magnetic elements 23 integral with one end and rotatable about a central longitudinal axis within a stationary housing or shear wall 24. The spinner 22 is receivable between a pair of positioning supports 25, 26 spaced apart along the central axis, and shown only generally. The upper support 25, seen only in fragmentary form, ~rovides a positioning seat for a non-rotating upper portion of the separator device 20. At the upper end also a magnetic drive 27 (not shown in detail) encompassing and magnetically coupling to the magnetic ele-~ ments 23 integral with the spinner 22, is rotated by a drive `~ 30motor 28. The lower support 2~ receives the lower end of the stationary housing 24 and defines an opening through which a plasma outlet 30 coaxial with the central axis may provide plasma as output.`
The sur~ace of the spinner 22 may be covered by a filter membrane 4n of a type conventionally used in blood filtration, and having surface apertures in the range of 0.1 to 1.0 microns. In the present system, however, substantial ~LZ~;~l76S

advantages are obtained by using membranes having particular physical characteristics and a pore size in the range of 0.8 to 1.0 microns, as described below. Under the membrane 40, the spinner surface is configured to define a plurality of circumEerential grooves 42, interconnected by longitudinal grooves ~4 which in turn communicate via radial conduits 46 with a central manifold 48. The manifold 48 is in communi-cation, through an end seal and bearing arrangement (not shown in detail) with the plasma outlet 30.
While blood from the donor is fe~ into the space between the spinner 22 and inner wall of the concentric housing 24 via a tangential blood inlet 50 coupled by a Elexible tubing (not shown in detail) to the blood input pump 16. A
high hematocrit return flow is taken from a tangential outlet ori~ice 52 spaced apart from the inlet along the longitudinal axis of the separator device 20. Flexible tubing (also not shown in detail) couples the outlet 52, through a peristaltic ~; packed cell pump 53 operated by a control 54, to a high hematocrit reservoir 55. Separator 20 operation can thereb~
be isolated from the donor so that alternate pump and return cycles can be use~l with a single needle device. Packed cells are reinfused in the donor at the needle means by a return pump 56 in a return line 57 between the needle means 12 and the reservoir 55. A return pump control 59 operates the return pump 56 at rates and times determined by the control system, ~hich may include means (not shown) for sensing the ;~ level in the reservoir 55.
In the current state o the art, it i5 pxeEerred to use a microprocessor 61 to monitor various conditions and to establish various controls, so that a number of operating ~ modes can be established and the system can operate automati-;; cally with a minimum of operator ~ttention. Many such features are provided in a practical e~ample of a system in accordance with the invention~ but only aspects germane to the present concept will be described, and it will be recognized that these particular features can also be provided by direct manual controls.

lZ6~65 The principal inputs to the microprocessor 61, for purposes o~ the present description, are taken from the trans-membrane pressure sensor coupled to the output of the blood input pump 14, and the flow rate Eor packed cell output estab-lished by the rate set at the packed cell pump control 54.
The flow rates for the packed cell output are derived at the microprocessor 61 by counting the number of revolutions at the pump 53. Other flow rates, and the motor speed if Aesired, can be fed back to the microprocessor 61, but these need not be described here.
The separator device 20, the mechanical operation of which is described in greater detail in the previously mentioned Fischel application, extracts plasma from the whole blood flow, through the membrane 40. The plasma flows through the membrane 40 into the circum~erential and longitudinal grooves 42, 44 on the spinner 22 surface and then into the central mani~old 48 via the radial conduits 46. The collected plasma in the central manifold 48 passes through the plasma outlet 30 to a plasma collection bag 62. The typical donor supplies two to three units of plasma in thirty to forty-five minutes, this being a rate consistent with blood supply from and high hematocrit return to the donor, without discomfort or substantial danger. ~s noted in the Fischel application, the rate of extraction remains substantially constant. Under proper operation, the plasma is clear and golden in color, being essentially completely free of cell damage and consequent ~ hemolysis.
;~i It is, however, extremely important to achieve maxi-mum reliable throughput of plasma, without trauma to the blood on the one hand or creation of a sensitive or unstable plasma-pheresis procedure on the other. Further beneits can then be derived in terms of the efficiency of plasma extraction, possible reduction of the cost of the expensive filter mem-brane, and the amount of donor time that is required. In accordance with the present invention, applicant departs en-tirely from the view that a controlled laminar flow must beestablished, with stratification of a plasma rich layer at -- ~Z6~765 the membrane surface, and with outward radial ~igration of cellular matter in the blood. Instead, applicant induces a strong vorticity in the form of successive, alternately circu-lating, annuli about the spinner and occupying the gap between the spinner and the shear wall. This vortex action is of a typè, referred to as Taylor vortices, first proposed by G. I.
Taylor in 1923 and described by him in Phil. Trans. Am., Vol.
233, pp. 289-293 in "Stability of a Viscous Liquid Contained Between Two Rotating Cylinders." Prior theoretical and computer simulation studies of the Taylor phenomenon (of which there are many) posit that the flow that is created in a Couette structure, under proper conditions, establishes a continuous sequence of annular vortex cells along the longitudinal axis of the cylinder. ~s seen in the fragmentary and ideali~ed vie~s of Figs. 2 and 3, which are not to scale, each cell has a circulatory flow within the plane of a cross-section that is radial to the central (rotational) axis ~; of the spinner, with the direction of circulation alternating between successive cells. The perspective view of Fig. 2 depicts the generally helical flows within an individual cell and the counter-rotation of alternate cells within the series.
The sectional view of Fig. 3 represents a computer generated approximation of flows within a cross-section e~tending along the spinner axis and at some radius relative to the axis.
The great majority oE prior studies, however, have been of stable liquid systems maintained under constant oper-ating conditions. Proposals for practicaL utilization of the effect have heretofore been limited, although the theoretical investigations have been and remain extensive in character.
The Taylor number, as it is now called, was defined by G. I. Taylor as the product oE the Reynolds number and the square root of thP gap between the rotor and housing divided by the square root of the radius of the rotor. The vortices be~in to appear, superimposed on the tangenti~l flow induced by the relative rotation, when the Taylor number is greater than 41.3. Many oE the investigations in the past have induced relative movement by spinning either the housing or the central mandrel, or both. In the examples given hereafter, only the central mandrel is spun, although the ~ilter membrane 40 may be disposed on the spinner 22 surface or on the stationary cell. It is also feasible to utilize the vortex action and other ~low conditions in a variety of other configurations and with other media, as discussed below.
Given the preferred example of the Fischel appli-cation, that of a 1" diameter spinner, 3600 r.p.m. rotation and a .027" gap, analysis has shown that the Fischel device actually operates in a region above the Taylor threshold.
Using these operative parameters, stable and conventional laminar flow would not be established unless the gap dimension were reduced to as low as .010", at which value shear levels would be excessive (for the given rotational rate) and hemoly-sis would occur. ~ significant feature of applicant's inven-tion is that vortex flow is not only permitted to occur, but is accentuated and strengthened by expansion oE the vortex cell sizes to occupy substantially the entire gap region and to provide tangential movement at substantial velocity across the membrane surface.
~ n important consideration, in accordance with the invention, is that the entire useful surface o~ the membrane ~ 40 i5 made to contribute to the extraction process even though -~ the suspension changes constantly because of filtrate extrac-;~ tion. The vortex action is augmented to the level at which the Taylor number is in excess of 70, and preferably in excess of 100, but usually not greater than about 250, through-out the length of the filter membrane despite the substantial increase in viscosity as plasma is extracted. Because the vortex cells fill the radial gap and sweep the membrane surEace in closely tangential relationship, velocity and force compo-nents of substantial magni.tude adjacent themembrane 40 surface .
are induced that are orthogonal to the ~orces induced by rotation of -the spinner 22. This circulating motion, coupled with convection along the spinner 22 axis, constantly seeks to remove any adherent cells from the sur~ace o~ the membrane 40 and replenishes available plasma for filtration through the ~ z~i~7~ 5 _ _ _ membrane pores. Any given point on the membrane 40 is swept in a time varying fashion by matter moving in alternately parallel and anti-parallel directions relative to the axis of rotation of the spinner. The circulatory forces that exist thus supplement the shear forces exerted on the blood by viscous drag, tangential to the spinning membrane 40 surface.
At the same time, as seen in Fig. 3, constant inter changes between adjacent cells take place, for both plasma and cellular components, although the plasma probably is transported longitudinally more readily than is the cellular matter. The interchange tends to substantially diminish any hematocrit gradient across the gap adjacent the spinner 22, although one can observe a color gradient increasing in inten-sity as one travels from the inlet to the outlet. Nonetheless the system achieves the desired effect of utilizing all incre-mental areas of the entire spinner 22 with substantially equal efficiency. Because the vortex cells are not static but are constantly moving downardly toward the outlet 52, any given incrernental area on the membrane is sequentially exposed to different vortex forces, militating against tendencies toward buildup of cell deposition. The scrolling motion of -the vortex cells as the blood mass moves causes the vortex cells to be angularly disposed or slanted relative to the central axis.
The circumferential rotation within the Taylor vortex cell must not impart so high a velocity that movement inwardly toward the rotating spinner impels red cells toward the membrane with sufficient velocity to induce cell deposition on the membrane. On the opposite side, impingement of cells against the stationary outer wall cannot be so vigorous as to induce damaging turbulence. Both of these conditions can occur with strong vortex action within a range of acceptable shear, the consequences on the one hand being clogging o~ the pores of the membrane with a concomitant incraase in transmem-brane pressure and a reduction of plasma flux, and on the other the introduction of cell damage and hemolysis.

~Z6~7~;5 Confirmation of the existence of the vortex cells has been derived in several ways. In contradistinction to the "shear centrifugation" theory substantial plasma fluxes or throughputs have been attained utilizinga membrane disposed at the stationary shear wall as described in conjunction with Figs. 6 and 7. It is evident that no signiEicant plasma extraction would result if the entire mass were centrifuged forcefully enough for cells to migrate radially outwardly an~
to pack against the outer surface. Also, although the spinner mass appears to be uniform when viewed through a transparent shear wall by the naked eye, the use of a synchronized strobo-scopic light and high speed flash photography clearly reveals the existence of the vortex cells. Under stroboscopic light, the vortices appear as in photographs deplcted in the prior art, as in Fig. 7 of an article by J. E. R. Coney et al entitled "A Study Of F~lly Developed, Laminar, Axial Flow ~nd Taylor Vortex Flow By Means Of Shear Stress Measurements," in O.-- Mech. ~nq. Sci., Volume 21, No. 1, 1979, pp. 19-24. Further, the vortex cell formation becomes even more visible when the separator is caused to function with a mixture of minute reflection crystals in water. Experiments were also conducted in which suspended matter, in the form of hollow micro-beads, were passed through the separator mechanism in a water suspen-sion. The system readily filtered the heavier water through the membrane, which again would not have taken place had there been a stratification of the heavier liquid outside the lighter particle matter. The theoretical existence of vortices is thus confirmed by a variety of direct evidence.
A different significant aspect of the invention re-lates to enhancement of the ffectiveness of the vortex action and concurrent reduction of traumatic incidents arising from selective control of surface characteristics of the membrane 40. The sweeping tangential flow in a vigorous vortex as practiced herein brings fragile red cells tin a blood flo~) into intimate but tangential relation to the membrane surfa`ce.
Although commercially available membranes appear solid and feel smooth (at least on one side) their submicron .

~2~L7~iS

characteristics can interact with much larger matter flowing across the surface. It is therefore preferred, in this plasmapheresis system, to employ a membrane having surface perturbations whose order of magnitude is smaller than the pore size. While a pore size o-E about 0.9 microns, for example, inhibits passage of red cells t a mean variation at the surface of less than that pore dimension assures a much greater freedom from capture or damage of the cells. A series of analyses using different membranes confirms that hemolysis (evidenced by increasing greater red coloration) increases in rou~h proportion to surface irregularities. In addition blockage by entrapment of cells appears as an increase in transmembrane pressure. While membranes can vary greatly in thickness (e.g. from 10 to 20 microns), surface protuberances and cavities should not exceed the stated relationship to pore size where blood is the medium.
A suitable membrane 40 is depicted in Fig. 8 as recorded on an electron micrograph. This specific membrane i5 a "Nuclepore" polycarbonate membrane; another often suitable membrane is the "Gelman polysulfone 650", but the sur~ace characteristics of this product appear to vary, perhaps because of the use of a surface surfactant. In contrast, a nylon membrane (e.g. "Cuno 66" produced by A~F) appears smooth and feels slipper~ to the touch but when examined at substantial magnification has a complex submicron surface pattern of protrusions and concavities. This type of surface is believed to generate local increases in shear stress and consequently to damage and entrap red blood cells to an extent ~hich is evident on visual inspection. Furthermore this particular irregular surface demonstrably acts to activate platelets which cumulativel~ interlock and build up a barrier on the membrane, blocking the pores~
The character of the membrane surface is also impor-tant from another aspect, because if surface activa-tion of cells commences during filtration~ it continues when the rotor is stopped as during a return cycle. Consequently during the time of use of a disposable there can be a substantial loss , ~............................ .

12~7~S

of porous surface and marked increase in transmembrane pres-sure.
Another important aspect arising from the existence of the strong vortex action pertains to a technique ~or clearing the membrane surface of occluding cells, or maintain-ing efficient operation. In the system of Fig. 1, the transmem-brane pressure is sensed by the pressure sensor 18 at the blood input, and a transmembrane (TMP) threshold pressure is selected based upon the sum oE three pressure components, namely:
A. The centrifugal "pressure" needed to force passage oE plasma from the outer edge of the spinner to the centerof rotation, calculated in accordancewith the following formula:
PCen~ - 1/2 p (CPM/60x2~)2 ~)2, where P is the density of plasma.
R is the radius of the spinner CPM is cycles or revolutions per minute B. The pressure needed to overcome pressure drop in the blood being transported through the s~stem. This drop is not a significant factor unless the gap or tubing dimensions are reduced substantially.
C. The pressure drop introduced b~ the flux of plasma across the membrane. For a typical Gelman polysulfone (0.65 micron pore size) membrane, and assuming a viscosity of 1.5 times the viscosity of w~ter, for which the pressure drop would be 0.15 mm Hgjml/min, the resistance factor of plasma would be ~.225 mm Hg~ml/min.
The sum of the three pressure components gives a theoretical TMP which assumes that 100% of the effective mem-braneis functioning properly. The theoretical TMP calculation is, howe~er, dependent on the pump rates, the hematocrit, the rpm and the diameter of the spinner as well as the flow characteristics oE the membrane. However, Eor a lli spinner, a gap of .030" and 3600 rpm, and assumiQg a hematocrit oE
40%, and a take of 70%, a threshold o~ 148 mm Hg is selected as a basic reference Eor typical donors. This is a typical 126~765 ..... . ... .

threshold level at the separator, without introducing a nega-tive pressure force arising from gravity feed to a collection bag. In practice selection within a range of 135 to 165 mm will typically allow for operation with diEferent donors, membranes and other variables.
If an increase of TMP above the selected threshold occurs, then the membrane may be assumed to be running at less than 100% effectiveness, so that blood cells are being deposited into the pores, or the membrane is acting to bind excessive protein/ or both. Protein binding can be avoided by selection of an appropriate membrane Eor this specific ap-plication. However, in accordance with the invention the membrane is kept at uniform efficiency or full performance, by responsive lowering of the percentage take in one of several ; different modes of operation. In a steady state mode, where changes are gradual, the operative rate of the packed cell pump 53 is lowered in proportion to the TMP change while holding input flow constant. The amount of decrease in plasma flow is controlled so as to reduce the suction efEect oE the plasma Elux across the membrane 40, increasing the significance of thesweeping vortex Elows to maintain TMPconstant. However, other modes of operation are feasible for specific TMP
variations. If TMP rises quickly or a predetermined amount, then ~ take can be reduced substantially by an incremental amount, so that the tangential vortex cell forces act to dislodge cells or prot~in from occluded pores. In practice, a 6 mm Hg variation in TMP (approximately 4~ increase) can be compensated for by a temporary reduction of10% in percentage take. Only a temporary reduction in plasma flux is needed, because the cleansing effect is seen very quickly. Sufficient tangential circulation is provided by the unique combination of rotor gap radius and surface velocity to remove lodged cells and proteins in only a few seconds. In other words the cleansing action is vigorous enough to make the great ma~ority of occlusions reversible. If the increase in TMP is too large and sudden, or if the % take reduction i5 tod large (e.g.
70%), the system may simply be shut down and checked.

.. . ..

The function of shear in separation of blood compo-nents has been widely studied'in the literature, and is regarded as essentially generating a lift force on cellular matter away from the membrane filter in a shear field. An article by Forstrom et al, entitled "Formed Element Deposition Onto Filtering Walls," in Trans. Am. Soc. Art. Int. Organs, XXl, 1975, pp. 602-607 seeks to quantify the onset of cell deposition by defining a deposition parameter in the following terms:
'~ 10 ~ Uf~/R2S3/2 Where v is the viscosity, U~ is the filtration velocity, R is the diameter of the cell, S is the wall shear rate, and ~ is a concentrate factor dependent upon the hematocrit.
Forstrom et al state that if the value of the deposi-tion parameter is greater than 0.343, cell deposition on the filter will occur if shear alone is the effective agent. In actuality, they found, by reviewing empirical studies, that ' deposition actually occurred in practical devices when the value of the deposition parameter became greater than 0.15.
This was determined from published reports at the critical point where filtration velocity begins to decrease due to occlusion of pore in the filter. Systems in accordance with the invention, however, exhibit practical results that are far above the theoretical barrier proposed by Forstrom et al.
A filter having 36.9 cm2 of membrane provides a plasma take of ' 45 microliter per minute, giving a filtration velocity of 0.020 cm/sec (for 75~ take of 40% hematocrit blood at 100 ml/min input). Using ~ = 17 with a hematocrit at 40, a value of 'R tthe red cell diameter) oE approximately 4.2 microns and a shear equal to 7500/sec, the Forstrom et al deposition param-eter calculates to 0.594. Filtration without excessive cell ~' deposition under such conditions would not, according to the Forstrom et al studies, be theoretically possible and should be even less feasible when compared -to prior empiricaI work.
Consequently, systems in accordance with the inven-tion utilize an entirely different filtration ~echanism and provide previously unobtainable increases in plasma fluxi :
. . . -~2617Ç~5 with respect to increase in shear. These increases may be seen from Fig. 4, which depicts the maximum stable plasma flux in relation to angular velocity for a given blood flow (100 ml/min). The curves re~resent the variations encountered as angular velocity is increased for different gap sizes under the otherwise stated conditions of gap, rpm and diameter. Up to certain levels the rate o~ increase is s`ubstantially linear, but thereafter the rate of increase Eollows a steeper slope.
In point of fact, 'he region at which the rate of increase in plasma flux rises to a higher slope can now be identified as the region of onset of the Taylor vortices. Using the previously stated Taylor equation to determine the onset of vortex cellsl Taylor flow begins in the 1100-1250 r.p.m. range for the 0.018" gap, at 2600 r.p.m. for the 0.012" gap and at above 460~ r.p.m. for the 0.008" ~ap. Although the shear rate of the smaller gap is substantially higher, so that plasma Elux should theoretically be greater if shear rate is the predominant eactor, this is the case only where the rpm's are low enough to be below the Taylor instability Eor the gaps shown in Fig. 4. Below 1000 r.p.m., for example, the smaller gap has superior plasma flux. In contrast, the larger gap provides significantly more plasma Elux, by a factor of several times, when vortex cells are properly established and have amplitudes that fill the gaps and provide vi~orous cell circu-lation. In preEerred examples, present systems operate at Taylor number in the range of 180-200.
Donnelly et al in "Experiments On The Stabiity Of Viscous Flow Between Rotating Cylinders, VI, Finite-Am-plitude," Proc. Ray Soc., London, Volume ~83, 1965, pp. 531-54 `- 30 established that t~e amplitude of the Taylor vortex varies ~- as the square root o-E the difEerence between the Taylor numberat the operating rpm and the critical Taylor number. Donnelly et al, however, used a slightly difEerent ~ormulation for the Taylor number where the Taylor number is proportional to the square of the rpm, so that a direct comparison to values derived from the préviously stated equation are nGt feasible.
Nevertheless, the amplitude of the vortex ceils increases .. . ..

with the Taylor number, the cells Eorming first at the rotating wall and expanding outwardly to fill the radial gap. When the vortex cell substantially fills the gap the action of viscous drag at the spinner surface provides local circumfer-ential ~orces that are much greater than comparable forces at the stationary outer wall. The vortex cell circulation provides sweeping moveme~t in the orthogonal direction at both walls, and it appears that this also is greater at the moving wall than the stationary wall. Vortex cell circulation at the outer wall can be increased to the level originally existing at the inner wall by increasing the rotor rpm. Either or both of the walls can include a filter membrane to achieve greater filtration efficiency than flat plate and other prior systems.
Because the amplitude of the Taylor vorticity in-creases more quickly than the shear rate as the rpm increases, the beneficial effects of ~aylor vorticity provide significant contribution to the high increase in plasma flux. Relatively larger size gaps provide an increase in Taylor vortex amplitude from a lower rpm threshold region and consequently a stronger vortex action at an acceptable shear rate. There is, however, a limit at which vorticity overpowers shear, with detrimental effects. This is primarily due to the radial inward tangential forces exerted during strong vortex action, which tend to cause cell deposition on the moving membrane. When this ` occurs, there is a decrease in the plasma flux, and an increase in the transmembrane pressure. As illustrated in Fig. 5, the use of a large gap size, 0.040", results in just such a diminution of performance. Fig. 5 shows variations in percent-age take relative to gap size, given a rotational rate of 3600 r.p.m. It can be seen, from this Figure, that character-istics drop off substantially at gap sizes in excess of 0.030".
Clogging of the membrane requires the system to attempt to Eorce filtration and substantially increases problems with cell damage.
~ different lirniting aspect is the cèll disruption which can occur if vortex action is too strongf by virtue of - ~2~1765 radially outward movement of cells with such velocity that they impinge on the stationary wall, to cause hemolysis. This apparently, however, will occur subse~uen~ to the cell deposi-tion problem in most instances.
Hemolysis is to be avoided or kept to a minimum in plasmapheresis systems in accordance with the invention, but it must be recognized that there is no strictly de~ined value or limit as to the amount of permis~sible cell damage. Objective operative criteria~, such as the shear level, are not precise determinants of whether an unacceptable level o~ hemolysis will be introduced in these dynamic systems. Shear limits for flat plate de~ices were previously considered to be in the range of 7500 sec, but present systems using vortex cell action have operated without significant hemolysis at in excess oE 12,000/sec.
The same principles of vortex action may be utilized in conjunction with a substantially dif~erent configuration and application, as depicted in Figs. 6 and 7, to which reference is now made. This comprises a separator device 70 for diagnostic and other analytical applications, wherein small samples may be taken and separated into constituents for individual analysis. The device of Figs. 6 and 7 also pertains to blood separation, and the usage of separated plasma or serum, although in a diagnostic procedure. However, the principles o~ construction and operation will be recognized by those skilled in the art as being applicable to other separated constituents and to entirely difEerent liquid sus-pensions as well.
In the separator device 70 of Figs. 6 and 7, the cylindrical housing 72 is constructed as a separable member so that access can be had to the interior. In this e~ample the housing 72 is formed as a pair of split halves 74, 75 having integral top and bottom end portions providing a sub-stantially enclosed cell when joined together. The split halves 74, 75 are held together by retainers, such as clamping rings 77, 78. Seals (not shown) may be dispos~d between the abutting surfaces o~ the split halves 74, 75 as long as the : L2~765 .. ..

concentricity of the interior surface is maintained. The inner wall of each split half 74~ 75 is de~ined by one or more removable filter membranes 80, 82 attached as by a strippable adhesive to the adjacent lands 86 on a network 84 of grooves in the inner sur~aces of the housing, these groove networks 84 in each hal~ 74, 75 providing communicating paths through radial orifices 87 for plasma or serum flow between the inner sur~ace of the membrane 80 or 82 and an outlet port 90 or 92, respectively. The outlet ports 90, 92 Eor filtrate are connected together to provide effluent ~or fractionation or for analysis by associated instruments. As with the system of Fig~ 1, the conduit system under each membrane 80 or 82 provides adequate interconnected flow area to avoid the intro-; duction o~ substantial impedance to flow oE filtrate to the appropriate outlet port 90, 92. The membranes 80, 82 may be ; removed and replaced by detaching them from the adhe~ive back-ing, which need not be strong in view o~ the Eact that the housing 72 and membranes 80, 82 are stationary. However, the adhesive may also be dissolved by chemical means and a new adhesive applied, or a mechanical attachment structure may alternatively be utilized as long as the concentricity of the inner housing face is maintained. It will be appreciated that other types of internally accessible housing structures, including a chemical arrangementt removabl~ end covers and the like, may be employed for different applications.
The whole blood inlet 94 for this structure is coupled tangentially to the housing inner wall at a lower region of the houslng, while the outlet g6 is positioned tangentially to the inner wall adjacent an upper end of the housing 72. Within the housing 72 is mounted a cylindrical spinner 97, having an internal magnetic member 98 mounted intermediate its ends. The spinner may be a smooth, plated surface member having an outer diameter providing the chosen gap dimension relative to the inner wall of the housing 72 defined by the membranes 80, 82 and interconnècting housing wall segments. The end surfaces of the spinnèr 97 are also spaced apart from the end surfaces of the ho~sing 72 by a ~2Gi765 .

predetermined amount. The entire housing, in its mid region, is encompassed by a rotatable magnetic drive 100 arranged in operative relation to the magnet 98 within the spinner 97.
The drive is positioned wi-th a slight vertical displacement from the magnetic element 98, so as to tend to bias the spinner 97 upwardly and reduce the force of gravity acting against the bottom end wall o the housing~ End bearings 102, 103 support the spinner 97 for rotation about the central axis.
~ blood input system 106, which may comprise not only a source of whole blood but also a source of anticoagulant and saline solution if desired is coupled to the blood input to the system. A source of a rinsing solution 108 is alterna-tively coupled to the same input 94, the rinsing solution being substituted manually or automatically for the blood input. Plasma or serum filtered through the system is passed ~rom the outlet 96 ~o an analytical instrument 110. Typically, th2 whole blood sample need only be sufficient in size to enable a period of stable extraction of filtrate for a long enough time to obtain an adequate plasma or seru~ sample (typically in the range of 5 to 30 milliliters).
The operation of the system with whole blood input is again based upon establishment o~ enhanced vortex flow throughout the entire length of the ilter membranes 80, 82.
To this end, the magnetic drive 100 synchronously rotates the inner spinner 96 through its magnetic coupling with the mag-netic element 94 at a rotational velocity in the range of 3600 r.p.m., it being assumed that the spinner again is i approximately 1" in diameter. Using a gap of .018 to .030", suitably adjusted for blood viscosity and other conditions, vortices are created that fill the radial gap between spinner 97 and housing 72. The existence of vigorous vortices that entirely fill the gap is more cri-tical when the membrane surface is static than in the example of Fig. 1. Because the vortices start near the spinner surface and grow outwardly unti they sweep the outer wall it is desirable to insure that viscous damping losses at the stationary wall ~o not prevent suitably vigorous vortex action at the outer surface. Thus 126~7GS
. .

the Taylor number is increased 5-10% over the values previously given for the Fig. l systeml as by increasing the rotational speed. No hemolysis is observed when this change is made.
The centriEugal displacement effects imparted by the rotation of the inner spinner 97 that tend to deposit cellular matter and other heavier matter on the surface of the membranes 80, ~2 are overcome by the sweeping vortex motion at the membrane surface.
Practical systems in accordance with this example have achieved plasma filtration rates with average hematocrit ~38-44~ blood) far in excess of rates achieved by the best parallel plate technology previously known. The plasma flux for stable output without evidence of pore clogging was some 5-10% less than the 70% take and 39-~3 ml/min rate achieved ~by the system of Fig. l for a l" spinner. Plasma throughput was maintained without substantial diminution in properties during the extraction of 2-3 units (500-750 ml~ of plasma.
The plasma take is stable and amenable to achieving higher throughput by use Oe higher spin rates or other variables~
The effective membrane area can be relatively increased because the membrane being stationary needs only enough supporting surface to be held concentric. Consequently, this system demonstrates Eurther that the vigor of the augmented vortex condition and the sweeping action imparted by the orthogonal flow components at the membrane surface, have not only estab-lished a new filtration approach using high shear but that it also incorporates a signficantly effective cleaning action.
With stationary membranes 80, 82 about the spinner 97, the system oE Fig. 1 can provide successive samples of relatively small amounts o~ ~iltrate from inputs provided via the whole blood system ln6 from many different sources. In ~` a diagnostic system, where the characteristics of the plasma are serum alone are of concern, contamination is not a problem and the surface cleaning effected by the vortex action can maintain high filtration efeiciency ~or a substantial period of time. Alternatively, saline solutlon from th~ input system 106 can be provlded between whole blood samptes to effect .:

~L~6~76~i some clearing of the system, or as a ~urther alternative the membranes 80, 82 may be cleaned by use of rinse solution from the source 108. When filtration efficiency drops in unrecoverable fashion below a selected level, the system need only be stopped, the housing 72 emptied, and the housing 72 then opened and new filter membranes 80, 82 used to replace the previously used elements.
In the example of Figs. 6 and 7, passage of whole blood is from a lower input to a higher output, but the essential vortex action and scrolling advance of the vortex cells are unimpeded even though the net flow proceeds upwardly against ~ravity. As in the prior example the vortices do not remain fixed but translate upwardly in continuous fashion, thus constantly sweeping incremental areas of the surface of the filter membranes.
A number of other variations of this system, in-cluding its use for the concentration of red blood cells or platelets, will present themselves to those skilled in the art. The separator device may be fabricated as a low cost - 20 disposable, for diagnostic or conventional plasmapheresis applications. The housing structure for a disposable unit dealing with small blood samples may be configured so as to provide a retainer chamber for the packed cell output, enabling the unit, including the waste blood, simply to be disposed of following col~ection of the needed amount of filtrate.
While a number of forms and variatins in accordance with the invention have been described it will be appreciated that the invention is not limited thereto but encompasses all modifications and expedients within the scope of the appended claims.

~' , :. .

Claims (93)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. The method of filtering whole blood passing between a rotating spinner and a concentric shell without clogging a filter membrane on one of the surfaces comprising the steps of:
establishing a plurality of annular vortices in the liquid suspension about the spinner and adjacent the membrane by selection of the surface velocity of the spinner relative to the radial gap and the viscosity of the whole blood;
sensing the transmembrane pressure while maintaining a substantially constant extraction rate of filtrate through the membrane;
comparing the transmembrane pressure to a calculated trans-membrane pressure value of no greater than about 165 mm Hg for extraction with full membrane efficiency; and reducing the filtrate throughput while maintaining the vortex action to clean the membrane when the transmembrane pressure rises above the calculated value.

2. The method as set forth in claim 1 above, wherein the filtrate is plasma, wherein the calculated transmembrane pres-sure value is in the range of approximately 135 to 165 mm Hg and further including the steps of feeding the blood between the spinner and shell in the axial direction relative to the spinner, extracting the filtrate through the spinner and maintaining the Taylor number in the range of 75 to 250.

3. The method as set forth in claim 2 above, wherein the calculated transmembrane pressure value is in the range of approximately 148 mm Hg wherein the Taylor number is in the range or about 180 to 200, wherein the filter membrane filters matter of less than about 1 micron size, and wherein the shear rate is less than about 12000/sec.

4. A system for filtering plasma matter capable of pass-ing a membrane from a fluid suspension, comprising:
a housing body having a hollow interior and an inner surface substantially concentric with a central axis and including a plurality of surface grooves;
rotor means rotatable within the housing body, the rotor means having a smooth outer surface concentric with the inner surface of the housing body and spaced apart therefrom and further including magnetic means interior to the housing body;
means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body;
filter membrane means disposed on the inner surface of the housing body for passing the plasma to the surface grooves in the housing body;
conduit means in the housing body in communication with the surface grooves in the filter membrane means for collecting filtrate passing therethrough; and means magnetically coupled to the magnetic means of the rotor means for driving the rotor means at a rate selected relative to the tangential velocity of the rotor means, the space between the rotor means and the housing body and the physical characteristics of the fluid suspension to establish annular vortices about the rotor means substantially filling the space between the rotor means and the housing body.

5. The invention as set forth in claim 4 above, wherein the housing body comprises means for accessing the inner surface thereof and means for releasably attaching the filter membrane means thereto.

6. The invention as set forth in claim 5 above, wherein the means for accessing the inner surface comprises a split housing body and means coupled to said split body for releasably coupling the split body parts together.

7. A system for filtering plasma capable of passing a membrane from a blood suspension, comprising:
a housing body having a hollow interior and an inner surface substantially concentric with a central axis;
rotor means rotatable within the housing body, the rotor means having an outer surface concentric with the inner surface of the housing body and spaced apart therefrom;
means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body;
filter membrane means disposed on the inner surface of the housing body and comprising a membrane having a smooth surface with deviations less than a predetermined pore size selected to pass the plasma;
conduit means in the housing body in communication with the outer surface of the filter membrane means for collecting filtrate passing therethrough;
means coupled to the rotor means for driving the rotor means at a rate selected relative to the tangential velocity of the rotor means, the space between the rotor means and the housing body and the physical characteristics of the blood suspension to establish annular vortices about the rotor means substantially filling the space between the rotor means and the housing body;
means for sensing the transmembrane pressure;
controllable means for withdrawing unfiltered suspension fed between the rotor means and the housing body; and means responsive to the sensed transmembrane pressure for increasing the rate of withdrawing unfiltered suspension to enable internal cleaning of the filter membrane means by action of the annular vortices.

8. The invention as set forth in claim 7 above, wherein the membrane has a porosity in the range of 0.1 to 1.0 microns.

9. A blood constituent filtering system of the type which, in operation, produces a Couette flow having Taylor vortices within a gap area disposed between relatively rotating generally cylindrical surfaces, at least one of which includes a blood constituent filtering membrane having pores sized to filter out a blood constituent and for passing a filtrate therethrough, said system including:
first means for detecting from transmembrane pressure the onset of filter membrane pore clogging by cellular blood constituents; and second means for controlling at least one operating parameter of the filtering system to cause cleaning of the clogged pores by the sweeping action of blood constituents entrained in said Taylor vortices and passing adjacent said filtering membranes.

10. A blood constituent filtering system as in claim 9 wherein said first means comprises a pressure transducer monitoring the fluid pressure at the inlet to said gap area and wherein said second means comprises a controlled pump which is caused to reduce the flux of filtrate in response to excessive monitored pressure.

11. A blood consituent filtering system comprising:
a stationary housing having an inner wall portion;
a rotatable spinner disposed within the housing and having an outer wall portion disposed opposite said inner wall and defining a gap area therebetween capable of sustaining Couette flow having Taylor vortices within the gap area;
a filter membrane disposed on at least one of said wall portions and sized to filter out plasma while being constantly swept across by cellular blood constituents entrained in said Taylor vortices and thus tending to dislodge from the membrane any cellular blood constituents;
a fluid inlet to said gap area and thus to a first side of said filter membrane for passing blood constituents there-into;
a fluid outlet from said gap area passing concentrated cellular blood constituents therefrom;
a filtrate outlet communicating with the other side of said filter membrane for passing plasma;
means for monitoring the transmembrane fluid pressure across said filter membrane during system operation; and means for temporarily increasing the fluid flow passing through said fluid outlet from the gap area in response to transmembrance fluid pressure in excess of almost 165 mm Hg and thus causing a temporary reduction in filtrate flow rate through the membrane and enhanced sweeping of the filter mem-brane by cellular blood constituents and thus an enhanced self-cleaning membrane action.

12. A blood constituent filtering system as in claim 9 or 11 wherein said fluid membrane comprises orifices of a pre-determined nominal dimension and wherein the surface pertur-bations of the filter membrane are less in magnitude than said predetermined nominal dimension and wherein the Couette flow has a Taylor number in the range of 180 to 220.

13. A blood constituent filtering system as in claim 11 wherein said filter membrane is disposed radially outwardly with respect to a rotating spinner member but wherein blood constituents entrained in said Taylor vortices nevertheless sweep past the membrane surface in spite of centrifugation forces which act radically outwardly upon cellular blood constituents, and wherein said fluid inlet and outlet are positioned to produce fluid flow in said gap area which is directed against gravity forces.

14. A blood constituent filtering system as in claim 11 further comprising:
a source of rinsing fluid; and a further fluid inlet means communicating with said gap area and with said source of rinsing fluid for temporarily introducing said rinsing fluid into said gap while simultaneously temporarily reducing the input of blood constituents maintaining said Taylor vortices in the gap area to assist in clearing the membrane and restoring an efficient filtering action.

15. A blood constituent filtering system as in claim 9 or 11 wherein the filtering membrane comprises a membrane having a smooth surface with deviations less than a predetermined pore size, and the system includes means for sensing the transmembrane pressure, controllable means for withdrawing unfiltered blood constituents fed into the gap area and means responsive to the sensed transmembrane pressure for increasing the rate of with-drawing unfiltered blood constituents to enable internal cleaning of the filtering membrane by the vortex action.

16. A blood constituent filtering method of the type which utilizes a Couette flow having Taylor vortices within a gap area disposed between relatively rotating generally cylindrical surfaces, at least one of which includes a blood constituent filtering membrane having pores sized to filter out plasma and for passing the plasma therethrough, said method including:
detecting the onset of filler membrane pore clogging by cellular blood constituents; and controlling at least one operating parameter of the filtering system to cause cleaning of the clogged pores by the sweeping action of blood constituents entrained in said Taylor vortices and passing adjacent said filtering membrane.

17. A blood constituent filtering method as in claim 16 wherein said detecting step comprises monitoring the trans-membrane fluid pressure at the inlet to said gap area and wherein said controlling step comprises controlling the rate at which concentrated cellular blood constituents are withdrawn from said gap area.

18. A blood constituent filtering method as in claim 16 wherein:
said detecting step comprises monitoring the transmembrane fluid pressure across said filter membrane; and temporarily reducing the plasma flux passing through said filter membrane in response to transmembrane fluid pressure in excess of about 165 mm Hg.

19. A blood constituent filtering method as in claim 16 wherein said filter membrane includes orifices of a predetermined nominal dimension, wherein the surface perturbations of the filter membrane are less in magnitude than said predetermined nominal dimension, wherein said gap area fluid flow is directed against gravity, and wherein the Couette flow has a Taylor number in the range of about 180 to 200.

20. A blood constituent filtering method as in claim 16 or 18 wherein said filter membrane is disposed radially out-wardly with respect to a rotating spinner member but wherein blood constituents entrained in said Taylor vortices nevertheless sweep past the membrane surface in spite of centrifugation forces which act radially outwardly upon cellular blood constituents.

21. A blood constituent filtering method as in claim 16 further comprising:
temporarily passing rinsing fluid into said gap area in lieu of blood constituents while simultaneously maintaining said Taylor vortices to assist in clearing the membrane and restoring efficient filter action.

22. A blood constituent filtering method comprising:
relatively rotating two generally cylindrical surfaces spaced apart to define a longitudinally extending annular gap area along which a Couette flow of blood constituents having Taylor vortices is passed, with the Couette flow having a Taylor number in the range of about 180 to 200;
providing on the outer one of said cylindrical surfaces a blood constituent filtering membrane having pores sized to filter out a blood constituent while being continually swept by blood constituents entrained in said Taylor vortices and passing a filtrate radially outwardly through said membrane;
passing blood constituents into said gap area at a first location and extracting concentrated cellular blood constituents from said gap area at a downstream longitudinally spaced apart location; and extracting a filtrate from the radially outer side of said filtering membrane.

23. A blood constituent filtering method as in claim 22 wherein:
the innermost cylindrical surface is rotated at a rate selected relative to its diameter, the gap size and the physical characteristics of the blood constituents to establish a series of vortices along the central axis of the inner surface, the vortices comprising contiguous annuli about the inner surface and having internal vortex circulations that alternate in direction;
the blood constituents are fed into the gap area along the central axis of the inner membrane to maintain movement of the vortices therealong;
filtrate passing through the membrane is extracted;
the rotational rate of the inner surface is controlled to establish vortices of such strength that they substantially fill the gap area along the length of the membrane despite the extraction of filtrate; and wherein the vortices provide forces at the membrane surface orthogonal to shear forces established between the relatively moving surfaces, such orthogonal forces being substantial in magnitude relative to the shear forces at the innermost surface.

24. A blood constituent filtering method as in claim 23 including the steps of determining a threshold transmembrane pressure in the range of 135 to 165 mm Hg for substantially unrestricted flow through the membrane, comparing the current transmembrane pressure to the threshold pressure, and lowering the rate of extraction of filtrate when the threshold pressure is exceeded by the transmembrane pressure while maintaining the vortex action, such that the orthogonal forces at the membrane surface can act to clear material deposited on the membrane surface.

25. A system for filtering plasma from blood with a disposable unit, comprising:
a disposable cylindrical housing body including a cylindrical rotor therein, at least one of the housing and rotor having a membrane filter thereon with a pore size in the range of 0.1 to 1.0 microns, and plasma conduits therein for conducting plasma to a plasma outlet, the rotor including magnetic means therein, the housing body being spaced apart from the rotor to define an annular gap and including blood inlet means leading into the annular gap, spaced apart cell concentrate outlet means communicating with the annular gap, and plasma outlet means communicating with the plasma conduits;
magnetic drive means exterior to the housing body and magnetically coupling to the magnetic means in the rotor for rotating the rotor at a rotational velocity selected, relative to the diameter of the rotor and the annular gap to establish a Taylor number of 70 to 250 throughout the annular gap with a shear rate below 12,000/sec;
means coupled to the blood inlet means for feeding blood into the annular gap at a predetermined rate;
pressure sensor means communicating with the annular gap for sensing the transmembrane pressure of the blood in the annular gap;
means responsive to the transmembrane pressure for comparing the transmembrane pressure to a threshold pressure determined primarily by the pressures required to overcome centrifugal forces, system pressure drop, and plasma flux across the membrane, and generating a responsive control signal when the transmembrane pressure exceeds the comparison; and means responsive to the control signal for varying at least one flow rate in the system apart from the predetermined inlet rate to maintain the Taylor number in the range of 70 to 250 while reducing the tendency of blood cells to clog the membrane.

26. The system as set forth in claim 25 above, wherein the system further comprises a controllable packed cell pump coupled to the cell concentrate outlet means in the housing body responsive to the control signal, and wherein the cell concentrate rate is increased in response to a transmembrane pressure in excess of the threshold, to reduce the plasma flux across the filter membrane.

27. The system as set forth in claim 26 above, wherein the conditions of blood viscosity, annular gap dimension, rotor diameter and rotational rate establish Taylor vortices in the blood in the annular gap, wherein the reduced plasma flux en-hances the sweeping action of the Taylor vortices across the membrane filter, and wherein the means for comparing includes means for re-establishing steady state operation after the transmembrane pressure has been reduced.

28. The system as set forth in claim 25 above, wherein the threshold is set in the range of 135 to 165 mm Hg, wherein the Taylor number is in the range of 100 to 250, wherein the blood inlet rate is about 100 liters per minute and the membrane filter area is selected to provide two to three units of plasma in less than 45 minutes.

29. The system as set forth in claim 28 above, wherein the membrane filter has a relatively smooth surface, with surface protrusions no greater than about the pore size, wherein the membrane filter is disposed on the rotor, and wherein the blood inlet means and cell concentrate outlet means are spaced apart to provide flow against gravity forces.

30. The system as set forth in claim 29 above, wherein the membrane filter area is approximately 37 cm2, the rotor diameter is approximately 2.5 cm, the annular gap is in the range of 0.018" (0.0457 cm) to 0.030" (0.0762 cm) and the rotational velocity of the rotor is less than about 3600 rpm.

31. The system as set forth in claim 30 above, wherein the shear rate is about 7500/sec, the rotational velocity is in the range of 3000-3600 rpm, the transmembrane pressure is about 148 mm Hg, the Taylor number is about 180 to 200, and pore size is in the range of 0.8 to 1.0 microns.

32. The method of filtering about two to three units of plasma from whole blood in about 30 to 45 minutes using a rotary member positioned with a predetermined gap within a disposable housing, at least one of the rotary member and housing having a membrane filter surface and conduit means leading to a plasma outlet in the housing, comprising the steps of:
feeding blood into the gap between the rotor and housing at a predetermined rate;
rotating the rotary member within the housing at a rate selected relative to rotary member size, gap width and blood viscosity to establish Taylor vortices in the blood and cell concentrations through the length of the rotary member;
extracting plasma from the plasma outlet at the desired rate in steady state operation by controlling the rate of cell concentrate removal;
sensing the transmembrane pressure of blood in the gap as a measure of initiation of depositon of cellular matter on the membrane filter surface;
comparing the sensed transmembrane pressure to a threshold pressure sufficient to overcome forces needed for pumping plasma through the membrane but less than 165 mm Hg;
generating a control signal when the sensed transmembrane pressure exceeds the thresholds;
lowering the rate of plasma extraction while maintaining the Taylor vortices to effect cleaning of deposited cellular matter from the membrane filter surface; and returning to steady state operation after the transmembrane pressure has been reduced.

33. The method as set forth in claim 32 above, wherein the plasma extraction rate is reduced by increasing the rate of cell concentrate removal.

34. The method as set forth in claim 33 above, wherein the membrane filter is on the rotary member and wherein the threshold pressure is determined as the sum of the pressure needed to overcome centrifugal forces acting on the plasma, the pressure needed to overcome system pressure drop through the membrane filter, and the pressure needed to overcome system pressure drop other than the membrane filter, and wherein the threshold is in the range of 135-165 mm Hg.

35. The method as set forth in claim 33 above, wherein the predetermined blood feed rate is about 100 ml/min, wherein the Taylor number for blood in the annular gap is in the range of 180 to 200, wherein the shear rate is less than about 10,000/sec and wherein the plasma extraction rate is in the range of 35 to 45 ml/min in steady state operation.

36. The method as set forth in claim 35 above, wherein the shear rate is about 7500/sec, wherein the threshold is about 148 mm Hg, and wherein the rotary member is rotated at less than about 3600 rpm.

37. The method as set forth in claim 33 above, further comprising the step of introducing a rinsing agent into the annular gap while maintaining the Taylor vortex action.

38. The method of filtering a cellular suspension passing between a rotating spinner and an outer shell without clogging a filter membrane on one of the surfaces comprising the steps of:

establishing a plurality of annular vortices in the suspension about the spinner and adjacent the membrane;
sensing the transmembrane pressure while maintaining a desired extraction rate of filtrate through the membrane;
comparing the transmembrane pressure to a transmembrane pressure value calculated to achieve extraction of filtrate with desired membrane efficiency and without substantial damage to the cellular components; and reducing the extraction rate of filtrate while maintaining the vortex action to clean the membrane when the transmembrane pressure rises above the calculated value.

39. The method as set forth in claim 38 above, wherein the cellular suspension is whole blood and the filtrate is plasma, and wherein the calculated transmembrane pressure value is no greater than about 165 mm Hg.

40. The method as set forth in claim 39 above, wherein the calculated transmembrane pressure value is in the range of approximately 148 mm Hg.

41. The method set forth in claim 38 above and further including the steps of feeding the cellular suspension between the spinner and shell in the axial direction relative to the spinner, and extracting the filtrate through the spinner while maintaining the Taylor number in the range of 75 to 250.

42. The method set forth in claim 41 above and wherein the shear rate is less than about 12000/sec.

43. The method as set forth in claim 38 above wherein said step for reducing the filtrate extraction rate includes increasing fluid flow past the rotating spinner and the outer shell when the transmembrane pressure exceeds the calculated value, thereby causing the desired reduction in filtrate flow rate.

44. The method as set forth in claim 38 above wherein the desired extraction rate is maintained substantially constant when the transmembrane pressure is below the calculated value.

45. The method as set forth in claim 38 above and further including the step of introducing a rinsing fluid between the rotating spinner and the outer shell while the filtrate extraction rate is reduced to assist in cleaning the membrane.

46. A system for filtering a cellular suspension passing between a rotating spinner and an outer shell without clogging a filter membrane on one of the surfaces comprising, means for establishing a plurality of annular vortices in the suspension about the spinner and adjacent the membrane;
means for sensing the transmembrane pressure while maintaining a desired extraction rate of filtrate through the membrane;
means for comparing the transmembrane pressure to a transmembrane pressure value calculated to achieve extraction of filtrate with desired membrane efficiency and without substantial damage to cellular components; and means for reducing the extraction rate of filtrate while maintaining the vortex action to clean the membrane when the transmembrane pressure rises above the calculated value.

47. The system as set forth in claim 46 above wherein said means for reducing the filtrate extraction rate includes means for increasing fluid flow past the rotating spinner and the outer shell when the transmembrane pressure exceeds the calculated value, thereby causing the desired reduction in filtrate flow rate.

48. The system as set forth in claim 46 above wherein the desired filtrate extraction rate is maintained substantially constant when the transmembrane pressure is below the calculated value.

49. The system as set forth in claim 46 above and further including means for introducing a rinsing fluid between the rotating spinner and the outer shell while the filtrate extraction rate is reduced to assist in cleaning the membrane.

50. A system for filtering a cellular suspension, comprising:
a housing body having a hollow interior and an inner surface including a plurality of surface grooves;
rotor means rotatable within the housing body, the rotor means having an outer surface spaced from the inner surface of the housing body;
means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body;
filter membrane means disposed on the inner surface of the housing body for passing the plasma to the surface grooves in the housing body;

conduit means in the housing body in communication with the surface grooves in the housing body for collecting filtrate passing therethrough; and means magnetically coupled to the rotor means for driving the rotor means at a rate selected to establish annular vortices about the rotor means substantially filling the space between the rotor means and the housing body.

51. The invention as set forth in claim 50 above, wherein the housing body comprises means for accessing the inner surface thereof and means for releasably attaching the filter membrane means thereto.

52. The invention as set forth in claim 51 above, wherein the means for accessing the inner surface comprises a split housing body and means coupled to said split body for releasably coupling the split body parts together.

53. A system for filtering a cellular suspension, comprising, a housing body having a hollow interior and an inner surface including a plurality of surface grooves;
rotor means rotatable within the housing body, the rotor means having an outer surface spaced from the inner surface of the housing body;
means for feeding the fluid suspension into the space between the rotor means and the inner surface of the housing body;
filter membrane means disposed on the inner surface of the housing body for passing the filtrate to the surface grooves in the housing body;

conduit means in the housing body in communication with the surface grooves in the housing body for collecting filtrate passing therethrough; and means on said housing body for accessing the inner surface thereof and means for releasably attaching the filter membrane means thereto.

54. The invention as set forth in claim 53 above, wherein the means for accessing the inner surface comprises a split housing body and means coupled to said split body for releasably coupling the split body parts together.

55. A system for filtering a cellular suspension, comprising:
a housing body having a hollow interior and an inner surface;
rotor means rotatable within the housing body, the rotor means having an outer surface space from the inner surface of the housing body;
means for feeding the cellular suspension into the space between the rotor means and the inner surface of the housing body;
filter membrane means on at least one of the inner surface of the housing body and the outer surface of the rotor means;
conduit means in communication with the filter membrane means for collecting filtrate passing therethrough;
means for driving the rotor means at a rate selected to establish annular vortices within the space between the rotor means and the housing body substantially filling the space between the rotor means and the housing body;
means for sensing the transmembrane pressure;

controllable means for maintaining a desired filtrate extraction rate through the membrane means; and means responsive to the sensed transmembrane pressure for reducing the extraction rate of filtrate while maintaining the vortex action when the transmembrane pressure rises above a calculated value to clean the filter membrane means by action of the annular vortices.

56. The invention as set forth in claim 55 above, wherein the membrane has a porosity in the range of 0.1 to 1.0 microns.

57. The invention as set forth in claim 55 wherein the cellular suspension is whole blood and the filtrate is plasma, and wherein the calculated transmembrane pressure value is no greater than about 165 mm Hg.

58. The invention as set forth in claim 55 wherein said means for reducing the filtrate extraction rate includes means for increasing fluid flow through the space between said rotor means and the inner surface of the housing body when the trans-membrane pressure exceeds the calculated value, thereby causing the desired reduction in filtrate flow rate.

59. The invention set forth in claim 55 wherein the membrane comprises orifices of a predetermined nominal dimension and wherein the surface perturbations of the membrane are less in magnitude than said predetermined nominal dimension and wherein the Taylor number in the range of 180 to 220.

60. The invention set forth in claim 55 wherein the membrane is on the inner surface of the housing body.

61. The invention set forth in claim 55 wherein the membrane is on the outer surface of the rotor means.

62. The invention set forth in claim 55 and further comprising:
a source of rinsing fluid; and means communicating with the space between the rotor means and housing body and with said source of rinsing fluid for temporarily introducing said rinsing fluid into said space while simultaneously temporarily reducing the input of blood suspension into the space while maintaining the Taylor vortices in the space to assist in clearing the membrane and restoring an efficient filtering action.

63. A blood constituent filtering system of the type which, in operation, produces Taylor vortices within a gap area disposed between relatively rotating generally cylindrical surfaces, at least one of which includes a blood constituent filtering membrane to filter out a blood constituent and for passing a filtrate therethrough, said system including:
first means for detecting the onset of filter membrane pore clogging by cellular blood constituents; and second means for controlling at least one operating parameter of the filtering system to cause leaning of the clogged pores by the sweeping action of blood constituents entrained in said Taylor vortices and passing adjacent said filtering membranes.

64. A blood constituent filtering system as in claim 63 wherein said first means comprises means for monitoring the fluid pressure at the inlet to said gap area and wherein said second means comprises means for reducing the flux of filtrate in response to monitored pressure.

65. A blood constituent filtering system as in claim 64 wherein:
said monitoring means detects the transmembrane fluid pressure across said filter membrane; and wherein said second means reduces the plasma flux passing through said filter membrane in response to transmembrane fluid pressure in excess of about 165 mm Hg.

66. A blood constituent filtering system as in claim 63 wherein said fluid membrane comprises orifices of a predetermined nominal dimension and wherein the surface perturbations of the filter membrane are less in magnitude than said predetermined nominal dimension and wherein the Taylor number is in the range of 180 to 220.

67. A blood constituent filtering system as in claim 63 wherein said filter membrane is disposed radially outwardly with respect to a rotating spinner member.

68. A blood constituent filtering system as in claim 63 wherein said filter membrane is located on the rotating spinner.

69. A blood constituent filtering system as in claim 63 further comprising:
a source of rinsing fluid; and a further fluid inlet means communicating with said gap area and with said source of rinsing fluid for temporarily introducing said rinsing fluid into said gap while simultaneously temporarily reducing the input of blood constituents maintaining said Taylor vortices in the gap area to assist in clearing the membrane and restoring an efficient filtering action.

70. A blood constituent filtering system as in claim 63 wherein the filtering membrane comprises a membrane having a surface with deviations less than a predetermined pore size, and the system includes means for sensing the transmembrane pressure, controllable means for withdrawing unfiltered blood constituents fed into the gap area and means responsive to the sensed transmembrane pressure for increasing the rate of with-drawing unfiltered blood constituents to enable internal cleaning of the filtering membrane by the vortex action.

71. A blood constituent filtering method of the type which produces Taylor vortices within a gap area disposed between relatively rotating surfaces, at least one of which includes a blood constituent filtering membrane to filter out plasma and for passing the plasma therethrough, said method including:
detecting the onset of filler membrane pore clogging by cellular blood constituents; and controlling at least one operating parameter of the filtering system to cause cleaning of the clogged pores by the sweeping action of blood constituents entrained in said Taylor vortices and passing adjacent said filtering membrane.

72. A blood constituent filtering method as in claim 71 wherein said detecting step comprises monitoring the trans-membrane fluid pressure at the inlet to said gap area and wherein said controlling step comprises controlling the rate at which concentrated cellular blood constituents are withdrawn from said gap area.

73. A blood constituent filtering method as in claim 72 wherein:
said detecting step comprises monitoring the transmembrane fluid pressure across said filter membrane; and temporarily reducing the plasma flux passing through said filter membrane in response to transmembrane fluid pressure in excess of about 165 mm Hg.

74. A blood constituent filtering method as in claim 72 wherein said filter membrane includes orifices of a predetermined nominal dimension, wherein the surface perturbations of the filter membrane are less in magnitude than said predetermined nominal dimension, and wherein the Taylor number is in the range of about 180 to 200.

75. A blood constituent filtering method as in claim 72 or 73 wherein said filter membrane is disposed radially outwardly with respect to a rotating spinner member.

76. A blood constituent filtering method as in claim 72 or 73 wherein said filter membrane is located on the rotating spinner.

77. A blood constituent filtering method as in claim 72 further comprising, temporarily passing rinsing fluid into said gap area while simultaneously maintaining said Taylor vortices to assist in clearing the membrane and restoring efficient filter action.

78. A blood constituent filtering method comprising, relatively rotating two surfaces spaced apart to define a longitudinally extending gap area along which a flow of blood constituents having Taylor vortices is passed, with the Taylor number being in the range of about 75 to about 250;
providing on the outer one of said cylindrical surfaces a blood constituent filtering membrane to filter out a blood constituent while being continually swept by blood constituents entrained in said Taylor vortices and passing a filtrate through said membrane;
passing blood constituents into said gap area at a first location and extracting concentrated cellular blood constituents from said gap area at a downstream longitudinally spaced apart location; and extracting the filtrate passing through said filtering membrane.

79. A blood constituent filtering method as in claim 78 wherein:
the innermost surface is rotated at a rate selected to establish a series of vortices along the central axis of the inner surface, the vortices comprising a contiguous annuli about the inner surface and having internal vortex circulations that alternate in direction;

the blood constituents are fed into the gap area along the central axis of the inner membrane to maintain movement of the vortices therealong;
filtrate passing through the membrane is extracted;
the rotational rate of the inner surface is controlled to establish vortices of such strength that they substantially fill the gap area along the length of the membrane despite the extraction of filtrate; and wherein the vortices provide forces at the membrane surface orthogonal to shear forces established between the relatively moving surfaces, such orthogonal forces being substantial in magnitude relative to the shear forces at the innermost surface.

80. A blood constituent filtering method as in claim 7 including the steps of determining a threshold transmembrane pressure in the range of 135 to 165 mm Hg for substantially unrestricted flow through the membrane, comparing the current transmembrane pressure to the threshold pressure, and lowering the rate of extraction of filtrate when the threshold pressure is exceeded by the transmembrane pressure while maintaining the vortex action such that the orthogonal forces at the membrane surface can act to clear material deposited on the membrane surface.

81. A system for filtering plasma from blood with a disposable unit, comprising:
a disposable housing body including a rotor therein, at least one of the housing and rotor having a membrane filter thereon with a pore size in the range of 0.1 to 1.0 microns, and plasma conduits therein for conducting plasma to a plasma outlet, the rotor including magnetic means therein, the housing body being spaced apart from the rotor to define an annular gap and including blood inlet means leading into the annular gap, spaced apart cell concentrate outlet means communicating with the annular gap, and plasma outlet means communicating with the plasma conduits;
magnetic drive means exterior to the housing body and magnetically coupling to the magnetic means in the rotor for rotating the rotor at a rotational velocity selected, relative to the diameter of the rotor and the annular gap to establish a Taylor number of 70 to 250 throughout the annular gap with a shear rate below 12,000/sec;
means coupled to the blood inlet means for feeding blood into the annular gap at a predetermined rate;
pressure sensor means communicating with the annular gap for sensing the transmembrane pressure of the blood in the annular gap;
means responsive to the transmembrane pressure for comparing the transmembrane pressure to a threshold pressure determined primarily by the pressures required to overcome centrifugal forces, system pressure drop, and plasma flux across the membrane, and generating a responsive control signal when the transmembrane pressure exceeds the comparison; and means responsive to the control signal for varying at least one flow rate in the system apart from the predetermined inlet rate to maintain the Taylor number in the range of 70 to 250 while reducing the tendency of blood cells to clog the membrane.

82. The system as set forth in claim 81 above, wherein the system further comprises a controllable packed cell pump coupled to the cell concentrate outlet means in the housing body responsive to the control signal, and wherein the cell concentrate rate is increased in response to a transmembrane pressure in excess of the threshold, to reduce the plasma flux across the filter membrane.

83. The system as set forth in claim 82 above, wherein the conditions of blood viscosity, annular gap dimension, rotor diameter and rotational rate establish Taylor vortices in the blood in the annular gap, wherein the reduced plasma flux enhances the sweeping action of the Taylor vortices across the membrane filter, and wherein the means for comparing includes means for re-establishing steady state operation after the transmembrane pressure has been reduced.

84. The system as set forth in claim 81 above, wherein the threshold is set in the range of 135 to 165 mm Hg, wherein the Taylor number is in the range of 100 to 250, wherein the blood inlet rate is about 100 litres per minute and the membrane filter area is selected to provide two to three units of plasma in less than 45 minutes.

85. The system as set forth in claim 84 above, wherein the membrane filter has a relatively smooth surface, with surface protrusions no greater than about the pore size, wherein the membrane filter is disposed on the rotor, and wherein the blood inlet means and cell concentrate outlet means are spaced apart to provide flow against gravity forces.

86. The system as set forth in claim 85 above, wherein the membrane filter area is approximately 37 cm2, the rotor diameter is approximately 2.5 cm, the annular gap is in the range of 0.018" (0.0457 cm) to 0.030" (0.0762 cm) and the rotational velocity of the rotor is less than about 3600 rpm.

87. The system as set forth in claim 86 above, wherein the shear rate is about 7500/sec, the rotational velocity is in the range of 3000-3600 rpm, the transmembrane pressure is about 148 mm Hg, the Taylor number is about 180 to 200, and pore size is in the range of 0.8 to 1.0 microns.

88. The method of filtering about two to three units of plasma from whole blood using a rotary member positioned with a predetermined gap with a disposable housing, at least one of the rotary member and housing having a membrane filter surface and conduit means leading to a plasma outlet in the housing, comprising the steps of:
feeding blood into the gap between the rotor and housing at a predetermined rate;
rotating the rotary member within the housing at a rate selected relative to rotary member size, gap width and blood viscosity to establish Taylor vortices in the blood and cell concentrations through the length of the rotary member;
extracting plasma from the plasma outlet at the desired rate in steady state operation by controlling the rate of cell concentrate removal;
sensing the transmembrane pressure of blood in the gap as a measure of initiation of deposition of cellular matter on the membrane filter surfaces;
comparing the sensed transmembrane pressure to a threshold pressure sufficient to overcome forces needed for pumping plasma through the membrane but less than 165 mm Hg;

generating a control signal when the sensed transmembrane pressure exceeds the thresholds;
lowering the rate of plasma extraction while maintaining the Taylor vortices to effect cleaning of deposited cellular matter from the membrane filter surface; and returning to steady state operation after the transmembrane pressure has been reduced.

89. The method as set forth in claim 88 above, wherein the plasma extraction rate is reduced by increasing the rate of cell concentrate removal.

90. The method as set forth in claim 89 above, wherein the membrane filter is on the rotary member and wherein the threshold pressure is determined as the sum of the pressure needed to overcome centrifugal forces acting on the plasma, the pressure needed to overcome system pressure drop through the membrane filter, and the pressure needed to overcome system pressure drop other than the membrane filter, and wherein the threshold is in the range of 135-165 mm Hg.

91. The method as set forth in claim 89 above, wherein the predetermined blood feed rate is about 100 ml/min, wherein the Taylor number for blood in the annular gap is in the range of 180 to 200, wherein the shear rate is less than about 10,000/sec and wherein the plasma extraction rate is in the range of 35 to 45 ml/min in steady state operation.

92. The method as set forth in claim 91 above, wherein the shear rate is about 7500/sec, wherein the threshold is about 148 mm Hg, and wherein the rotary member is rotated at less than about 3500 rpm.

93. The method as set forth in claim 89 above, further comprising the step of introducing a rinsing agent into the annular gap while maintaining the Taylor vortex action.