CA1261217A

CA1261217A - Single needle blood fractionation system having adjustable recirculation through filter

Info

Publication number: CA1261217A
Application number: CA000455157A
Authority: CA
Inventors: Arnold C. Bilstad; Richard I. Brown; Robert J. Kruger
Original assignee: Baxter International Inc
Current assignee: Baxter International Inc
Priority date: 1983-05-26
Filing date: 1984-05-25
Publication date: 1989-09-26
Also published as: EP0128683A3; DE3475872D1; JPS605164A; EP0128683A2; EP0128683B1; JPH0477588B2; US4605503A

Abstract

SINGLE NEEDLE BLOOD FRACTIONATION SYSTEM
HAVING ADJUSTABLE RECIRCULATION THROUGH FILTER

Abstract of the Disclosure A single needle batch-type blood fractionation system for separating plasma from whole blood includes a disposable flow sys-tem having a single-lumen phlebotomy needle and associated donor conduit, a flow-through plasma separation filter, and an in-process fluid reservoir. During an initial draw cycle whole blood is pumped through the filter to the in-process reservoir by a peristaltic-type inlet pump operating at a predetermined draw rate. When a predetermined volume of filtered plasma-deficient blood has been collected in the reservoir, as sensed by the weight of the reservoir the system reverts to a return cycle wherein a portion of the plasma deficient blood in the reservoir is pumped back to the donor con-duit by a peristaltic-type return pump operating at a predetermined return rate higher than the draw rate of the inlet pump. Depending on the relative operating speeds of the inlet and return pumps, an operator-controllable portion of the plasma-deficient blood from the in-process reservoir is returned to the donor through the phle-botomy needle, and the remaining portion is recirculated through the filter. The partial recirculation of plasma-deficient blood through the filter during the return mode reduces the processing time of the system, provides for improved accommodation of whole blood of unusually high or low hematocrit, and enables the use of a smaller and less expensive filter.

Description

SPECIFICATION
~ackground of the Invent _ The present invention relstes generally to systems and apparatus for processing whole blood, and more specifically to S blood fractionation systems and apparat:us having a filter com-ponent for separating and collecting a de~ired blood component, such as plasma, from whole blood through a single-lumen phlebotomy needle.
Various method~ and apparatus h~ve been ~eveloped Eor the in vivo processing of whole blood, wherein whole blood is takPn from ~ donor, a de~ired blood component is separated and collected, and the processed blood ~s returned to the donor. ~lood components typically coll~cted using such processing include plasma (plasmapheresis), white blo~d cells (leukopheresis) and platelets (plateletpheresis).
In vivo blood pr w ~ssing app~ratu~ m~y be o~ the cen-trifugal type, wherei~ the differing density o4 the collected blood component cau~e~ the compone~t to congregate for collection at a particular radial distAnce in a centrifugc, or may he of the filter typ~, wherein the particle size o t~e collected com-ponent ~llow~ only that component to pa~s through a ~ilter membrane into a collection cha~b~r. Filter type app~ratu~ is generally pref~rable for in vivo plasmapheresis applications. since such apparatus does not require complex rot~ting machi~ery and is more compact ~nd leAs costly to manufacture.

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: , ~: ' One Eorm of filter which is particularly attractive for use in plasmapheresis apparatus utilizes a plurality of parallel microporous hollow fibers arranged side-by-side in the form of a bundle within a hollow cylinder. As whole blood is caused to flow through the fibers the plasma component passes through the walls of the fibers to the surrounding container, which forms a collection chamber from which the component is transported to a collection container.
The efficiency of a flow-through filter in separating plasma from whole blood depends on the hematocrit of the donor, and the flow rate and pressure of the whole blood as it is pumped through the filter.
Insufficient flow rates or whole blood pressures result in less than optimum yields. Excessive flow rates or whole blood pressures result in hemolysis, or damage to the red blood cells, within the filter, and possible failure of the filter to exclude red blood cells from the collected plasma. Thus, a practical limit exists for the percentage of plasma that can be recovered by a flow-through membrane filter in a single pass of whole blood~
To improve the efficiency of blood fractionation systems it has been proposed that once-filtered plasma-deficient whole blood be recirculated through the filter. This enables the filter to refilter the previously-filtered whole blood, recovering an additional percentage of the remaining plasma component.
However, in certain procedures, as where a high hematocrit is encountered in the whole blood drawn from a donor, the hematocrit of the once-filtered plasma-deficient whole blood may be so high as to require a reduction in the filter flow rate and pressure with an attendant reduction in filter efficiency, to avoid hemolysis in the second pass through the filter.
This has the effect of increasing the time required to separate a given quantity of plasma, thereby increasing the inconvenience of the procedure to the donor.
; Accordingly, the need has developed for a blood . .
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-..~', ~ ' fractionation system wherein recirculation through the filter is obtained while maintaining hematocrit, flow rate and pressure parameters which provide optimum system e~ficiency.
Furthermore, for user comfort it is desirable that in vivo blood fractiona-tion systems withdraw and return whole blood to the donor through a single phlebotomy needle at a single injection site. This necessitates either the use of a single dual-lumen phlebotomy needle, in conjunction with a continuous flow non-batch system, such as described in IJ.S. Patent No. 4,447,191 of Arnold C. Bilstad et al, entitled "Blood Fractionation Apparatus", or of a single-lumen phlebotomy needle in conjunction with a bidirectional batch system, whereby batches of whole blood are alternately drawn through the needle, passed through a plasma separation filter, and returned through the same needle. Such bidirectional single-lumen batch systems have the advantage of utilizing a smaller and potentially less traumatic single lumen needle. However, since such systems have heretofore not provided plasma separation from the batch in process during both the draw and return cycles, they have undesirably prolonged the time required to collect a desired volume of plasma.
The present invention is directed to a bidirectional single-needle batch type blood fractionation system which provides for user-controlled partial recirculation of plasma-deficient whole blood through the system filter during the blood return cycle, thereby enabling optimum plasma separation efficiency to be maintained in the system notwithstanding variations in whole blood hematocrit. Basically,'whole blood is drawn from the donor through a single phlebotomy needle and associated bidirectional donor conduit and pumped through the filter to a reservoir by an inlet pump. As the whole blood passes through the filter plasma is separated and stored in a separate collection container.
Upon reaching a predetermined volume, filtered plasma-deficient whole blood in the reservoir is pumped ~i.
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'7 -from the reservolr to the donor conduit by a return pump, which operates at a higher rate than the inlet pump. By reason of the higher rate of the return pump Elow is reversed in the donor condui-t and a portion of -the plasma-deficient whole blood is returned to the donor through the phlebotomy needle, and the remaining portion is recirculated through the filter, without the need for valves for controlling fluid flow in the system. By controlling the relative speeds of the inlet and return pumps, the portion of the plasma-deficient whole blood from the reservoir recirculated through the filter can be varied to maintain a desired hematocrit at the filter.
The present invention, by increasing the plasma separation efficiency of the system, makes a reduction in the volume of the system filter possible. This is advantageous in that it reduces the quantity of extracorporeal blood in process, and the cost of the system filter and the microporous filter material utilized therein.
Accordingly, it is an object of an aspect of the present invention to provide a new and improved fluid fractionation system for separating a fluid fraction from whole fluid.
It is an object of an aspect of the present invention to provide a new and improved blood fractionation system for separating plasma from whole blood.
It is an object of an aspect of the present invention to provide a filter-type blood fractionation system having reduced in-process volume.
It is an object of an aspect of the present invention to provide a filter-type blood fractionation system having improved plasma separation efficiency.
It is an object of an aspect of the present invention to provide a new and improved filter-type blood fractionation system having user-controllable recirculatlon through the filter.

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It is an object of an aspect of the present invention to provide a new and improved blood fractionation system utilizing a single lumen needle.
It is an ob~ect o~ an aspect of the present invention to provide a valveless single-lumen needle blood ~ractionation system.
Summary of the Invention Various aspects of the invention are as follows:
A single needle blood fractionation system for separating a blood fraction :Erom whole blood, comprising:
means including a donor interface conduit adapted for connection to a phlebotomy needle and alternately operable in forward and reverse flow for alternately receiving and returning blood from a donor;
an intermediate fluid reservoir;
means including a first conduit connecting said donor conduit to said intermediate fluid reservoir;
means including a flow-through filter disposed in said first conduit for separating the desired blood fraction from whole blood flowing through said filter;
means including a second conduit connecting said intermediate fluid reservoir and said donor interface conduit;
an inlet pump for pumping fluid through said first conduit to said reservoir;
a return pump for pumping fluid from said intermediate reservoir through said second conduit;
system control means responsive to the volume of fluid in said intermediate reservoir for initiating operation of said return pump in response to said volume reaching a predetermined maximum level, and for terminating operating of said return pump upon said volume reaching a predetermined minimum level; and the rate of said return pump being adjustable relative to the rate of said inlet pump whereby upon operation of said return pump an operator selectable portion of the filtered blood in said second conduit is i : .

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caused to recirculate through said first conduit and said fil-ter.
The method of separating a blood component from whole blood, utilizing a phlebotomy needle, and flow-through separating means, comprising the steps of:
pumping in whole blood drawn through the needle through the separation means;
collecting the component-deficient blood from the separation means in a reservoir;
initiating pumping bac]c component-deficient blood from the reservoir to the needle upon the volume of blood in the reservoir rising above a predetermined level;
said pumping back being at a higher rate than said pumping in whereby the volume of blood in the reservoir is caused to diminish; and terminating pumping back from said reservoir upon the volume in the reservoir falling below a predetermined minimum level.
By way of added explanation, in one aspect the invention is directed to a single needle blood fractionation system and apparatus for separating plasma from whole blood. In one form the system includes a disposable flow system comprising a phlebotomy needle and an associated bidirectional donor interface conduit r flow-through separation means for separating plasma from whole blood, and an intermediate storage reservoir. An inlet pump is provided to pump whole blood from the donor interface conduit through the filter to the intermediate storage reservoir. A return pump operable at a rate greàter than the rate of the inlet pump urges plasma-deficient whole blood from the reservoir to the donor interface conduit. System control means responsive to the volume of whole blood in the intermediate storage reservoir initiate operation of the return pump upon the whole blood in the reservoir reaching a predetermined maximum volume and terminate operation of the return pump upon the whole blood in the : . . . ~
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, . , reservoir reaching a predet~rmined minimum volume. By reason of the rate of the return pump being greater than the rate of the inlet pump, upon operation of the return pump a portion of the plasma-deficient whole blood from the reservoir dcpendent on th~
ratio of the pump rates is ~aused to recirculate through the in-let pump to to separation means, and thl~ remaining portion D~ the plasma-deficient whole blood i9 cau~ed to flow through the donor inter~ace conduit to the donor.
BrieE Description of the Drawin~s The features of the pr~sent invention which are be-liev~d to be novel ar~ ~et forth with particularity in the appended claims. ~he invention, together with the ~urther ob-jects and ~dvant~ges thereo~, may best b~ uDder~tood by refer-ence to the following des ription taXen in conjunction with th~
lS accompanying drawing3, in the s~veral figures of which like re-ference numeral~ identify l~ke elements, and in which:
Figure 1 i~ a perspe~tive view-o a single-needle partial-recirculation plas~pheresis bloo~ ~ractionation system constructed in accordance wi~h the inventioA.
2D Figur~ 2 is a functional block diagra~ showing the prin-cipal cQmponents of ~he bloo~ fr~ction~tion syste~ of Figure 1.
Figure 3 i9 an enlarged fr~nt ele~ational view of the con~rol panel of the blood fractionation appara~us of Figure 1.
Figure 4 i9 an enlarged front elev~tio~al view partially in section showing the electrical weight transducer of the ~ystem .~

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in conjunction with the in-process fluid reservoir of the system.
Figure 5 is a simplified schematic diagram of the mode control circuit of the blood fractionation system.
Figure6a is a simplified srhematic diagram of the lnlet pump motor control circuit of the blood fr~ctionation ~ystem.
Figure 6~ is a simplified schematic diagram of a portion of the return pump motor control circuit o~ the bIood fraction-ation system.
Figure 7 is a simplified schematic diagram of the ACD
pump drive circuit of the blood fractionation syst~m.
Pigure ~a is a simplified flow diagram of the blood fraction~tion system showing the system in the draw portion of its operating cycle.
Fiyure 8b is a flow diagram similar to Figure Ba showing the blood fractionation system adapted for recirculation in the return portion of its operating cycle.
Figure 8c is a flow diagram similar to Figure ~a showing the blood fractionation 3ystem adapted for non-recirculation in the return portion of its oper~ting cycle.
Figure 8d is a flow diagram similar to Pigure 8a showing the plaQ~apheresis sy tem in its prime mode.
Figure 9 i~ a simplified depiction of plasma collection versus time us~ful in comparing the operation o~ ~arious types of blood fractionation sy~tems.
Figure 10 is a simplified depiction of collected plasma volu~e versus time for various types of hlood fractionation sys-tems useful in comparing the systems.
Figure 11 is a top plan view of a disposable fluid cir-cuit for use in conjunction ~ith the blood ~ractionation sy~tem of the invention.
DescriDtion of the Preferred Embodiment Referring to the Figures, and particularly to Figure 1, a blood frActionation apparatus 20 ~or use in conjunction with .. :

a single-needle f}lter-type blood fractionation system having filt~r recircul~tion in accordanc~ with the invention is seen incorporated within a table-mounted housing 21. The housing pre-ferably includes ~ pair of v~rtical support pole3 22 and 23 fro~
which a hrrizontal bar 24 is mounted to allow a pl~rality of col-lection ~nd dispensing containers o~ conventional construction to be hung by means of appropriate hangers.
The fractionation apparatus 20 operates in conjunction wi~h a disposable 1uid circuit, generally identified by the reference numeral 25 in Figure 1 and shown schem~tiGally in Figure 2. The fluid circuit 25 includes a plurality of flexible plastic tubing seg~ents which form fluid conduits between various components of the fluid cireui~. As shown in Figure 2, whole blood derivsd from or returned to a donor iq conveyed through the lumen of a ~$ngle single-lumen phlebotomy ne~dle 26 and a bidi~ectional donor interface conduit sægment 27 ~o which the needle is connected. Conduit 27 communi~ate~ with a T-~onnector 28, which comm~nicates with a tubing segment 30. Whole blood is conveyed through tubing segment 30 and an inline mixing chamber 31 by a peristaltic-type inlet pump 32 to a hollow fi~er-typ2 flow-through filter 33. The operation of ~h~ inlet pump i5 mon-$tsred ~y ~ positive pres~ure (+P) ~onitor oi~cuit 3~ conne~ted to tubing segm~nt 30 by a short tub~ng ~eg~ent. N~sative prs3-sure, such ~s might occur upon the collapse of a vein, is mo~itored by means of ~ neg~ti~e pressu~e ~-P) monitor circuit 35 conne~ted .'.~

, . ~ , to tubing ~egment 30 upline of inlet pump 32 by another short tubing seg~ent.
To prevent blood f~om clotting while in p~ce~s anti-coagulant ~ACD) solution fro~ a ~upply container 36 i5 introduced S into conduit segment 30 through ~ tubing segment 37 and a ~-connector 38. ~ drip chamber 39 ~ay be provided inline in seg~ent 38 to moAitOr ACD flow. A peri3taltic-typ~ pump 40 is provided along tubing segment 37 to provide A controlled rate of addition of the antiroagulant ~luid to the whole blood.
Plasma separated from whole blood withln filter 33 is convey~d by a tubing segment 41 to ~ plasma collection container 42. The p~essure provided by inlet pu~p 32 providQ~ flow through filter 33 to the rollection container. A w~i~ht scale of con-ventional construction may be pzovided to pro~ide an i~dication to the user o~ the volu~e of pla8m~ collected.
Plasma-deficient blood f~om filt~r 33 i5 conveyed through a tubin~ seg~ent 43 to an in-process ~luid storage reser-voir 44. In accordance with the invention, this plasma-deficient blood is periodie~lly withdrawn fro~ reservoir 44 through a tubing segment 45 by a peristaltic type return pump 4S for return to condult 27 at T-oonnector 28. The whole blood conveyed through tubing Begm~nt 45 paYs~ through ~ combined bubble trap ~nd fluid absence det~to~ 47, ~hich ~ay be 6imilar in structure and oper-ation to that de~cribed in U.S~ P tent ~o. 4,341,116 to Arnold C. Bilstad ~t al.

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Reservoir 4~ and plasma container 42 are preferably hung at the same height to avoid the need for an equalizer valve at the whole blood and collected plasma outlets of filter 33. However, under other circumstances an equalizer valve may be provided to restrict the plasma outlet port until the pressure of the plasma in the filter reaches that of plasma-deficient blood flowing from the filter/ and thereafter to modulate plasma flow through line 41 to maintain the pressure equivalence. A preferred constructlon for such an equalizer valve is described in U.S. Patents 4,412,453 and 4,431,019. A transmembrane pressure (TMP) monitoring system 48, which may be as described in U.S. Patent 4,493,693 may be provided in apparatus 20 to assist the user in making adjustments for maximum operating efficiency of filter 33.
For system prlming purposes, a saline fluid may be added to segment 30 through a tubing segment 51, which is connected at one end to a saline container 52 and at its other end to a T-connector in conduit segment 30. A
second saline line 53 is provided between container 52 and bubble trap 47 for use in the purging procedure to enable trapped air to escape. Drip chambers ~ . ' ' ~ .

2~7 and clamps o~ conventional construction may be provided in lines 51 and 53 to assist the procedure. A ~a~ety clamp 54 positioned along tubing segment 45 downline of bubble trap 47 actuat~s in the event of detection of a bubbl~ or in th,~ event of D malfunction in ~he apparatus to preclude uncontrolled infus$on of fluid into the donor.
Referring to Figure 1, the blood fractionation apparatus 20 includes a sloped control panel 55 containing operator-actuated controls for operating the apparatus. A3 ~hown in Figure 3, con-trol panel 55 include~ a pair of selector ~witches 60a a~d 60b by which th~ dr~w and return mode op~ratlng ~pe~d~ of anticoagu-lant pu~p 40 are set, a pair of potentiometer controls 61a and 61b and a digit~l resdout 62 by which the dr~w ~nd return mode opera-ting speeds of the inlet pu~p 32 are controlled, and a pair of potentiometer control~ 63a and 63b and a digital readout 6~ by which the draw and return mode operating speeds of the return pump 46 are controlled. A plurality of push button switches 65 are pro-vided to ~stabli~h the operating mode oi th~ apparntus. A plurality of status indicating lights 66a-66f provide stat~s ~nd alarm indi-cations, ~nd three pairs of indicator lights 66g ~nd 66h a~sociated with respective on~ of the 3ystem p~p5 indic~te the dr~w and re-turn operating e~cles o~ the pu~ps. An emerg~ncy stop ~witch 67 proYide3 ~or an immediate operator-initiated shutdown in the event of a malfunction.
A display 68 display~ the t~tal volu~a of whole blood processed by the apparatus since the beginning of a particular procedure. A display 69 displays fluid pressure readings, as called fDr by a trio of pushbutton switches 69a-69c. Actuation of switch 69a causes the inlet pressure of filter 33 to be dis-played. A~tuation of switch 69b causes the coll~cted plasma S pressure of the filter to be displayed. Actuation of switch 69c causes the inlet transmembrane pressure ~TMP) of the filter to be displayed as derived by TMP monitoring circuit 48.
Referring to Figure 2, the inlet pump 32 is driven by a motor 70. Power for operating motor 70 i9 provided by a motor contlol circuit 72 which responds to potentiometer controls 61a and 61b and a tachometer feedback sign~l From a ta~hometer (not shown in Figure 2) as~ociated with the ~otor to maintain a desired motor operating speed. The tnl~t pu~p 10w r~te is dis-played by readout 62 as part of a display circuit whi~h responds lS to the tachometer ouSput signal.
Similarly, th~ return pump 4S i5 driven by a motor 76.
Power for motor 76 is provid~d by a motor control cireuit 78 which responds to a tachometer feedb~ck signal ro~ a tachometer (not shown in Figure 2) associated witb the motor and panel-mounted potentiomet~rs 63~ and 63b to maintain ~ desired constant motor speed. ~he return pump flow rate i3 displayed by readout 64 as part o~ the display circuit.
The anticoagulant pump 40 is driven by a stepper motor ~9. ~rive sign~ls for motor 79 are developed by a motor control circuit 80 which responds t~ E~te selection switches 60a and 60b ~6~7 to maintain a desir~d anticoagul~nt flow rate.
The op~ration of the various pump motors is controlled by a control circuit 81 which includes t:he mode select pushbutton switches 65 on control p~nel 55. Certai.n system.conditions, such as negative pressure at pres~ure monitor 35, or excessive posi-tive pressure at pressure monitor 34, or thç oc~usrence of a bubble or other fluid absence ~ ~ignaled at the output of the combined bubble trap and ~luid 3bsence detector ~7, xesult in the application of an alarm signal to control circuit 81. This cir-cuit in turn produc~s a control signal which i5 applied to ~otor control circuits 72, 78 and 80 by way of ~ ~otor cont~ol line 82 to inter~upt operation of the ~otoss. In addition, an alarm 83 associated with the contsol circui~ may be 30unded and an appro-priate one of indicator la~ps 66a-66f ~ay be lit to al~t the oper~to~. Each of motor con~rol circuits 72, 78 and 80 ~lso in-clud~s intern~l ~tall protection whereby an alarm signal is de-veloped and ~pplied to control circuit 81 by way of a control line 84 to terminate operation o~ blood fractionation apparatus 20 in the e~ent of a pump m~lfunction.
Baaically, the hollow fiber ~m'orane-type filter aevice 33 e~ploy~d in blood fra tionation apparatus 20 includes a gener-ally cylindric~l housing within wich a bundle of microporous hollow fibess ~re mounted. The hou~ing includes end caps wh~oh close ~he ends o the hou~ing to for~ n plas~a colle~tion chamber within th~ housing. A whole blood inlet port is formed on one :, , .

~nc cap, and a whole blood outlet port is formed on the other end cap. Blood introduced through the inlet port enters the adjoining open ends of the hollow ~iber membrane! elements and proceeds to flow lengthwise through the fibers. Plasma in the whole blood flows through the micropores in ~he hollow ~ibers and out into the collection chamber formed within the housing circumferentially surrounding the bundle. The housing includes two side plasma out-let port~ which c~m~uni~ate with ~he collection chamber. One out-let port communicate~ with the plasma collectlon container 42 to collect plasmn separated by the filter. The other outlet port is used to sen~e plasma outlPt pre~3ure in conjunction with a tubing segment 85, a pre3~ure tr~nsducer 36, and the transm~mbr ne pres-sure (TMP3 monitoring ~yqtem 48. Plas~a-deficient blood ~contain-ing r~d cells, leu~ocytes and platelet~), having p~ssed through lS ~he hollow fiber membrans ele~nts, exi3t~ through ths outlet port for temporary storaqe in th~ inter~ediate in-process fluid reier-voir 44.
In accordance with the invention, pla~ma-deficient whole blood in re~ervoir ~4 is periodically p~mp~d by return pump 46 back to do~or condult s~gment 27. Inlet pu~p 32 continu~s to operate at this time ~t a rate ~et by th~ oper~tor, ~o th~t a pDrtiO~ of the returned plasma-deficient blood ~ependent on the ratio of She return pump rate ~o the whole pu~p rate is recirculated through filter 33, thereby continuing plasma collection ~uring the return cyclsO Por exsmple, with inlet pump 3~ continuously operating at 60 ml./min., and return pu~p 46 operating at lP0 ml./min., 60 ml./

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min., or 60~ of the processed plasma-deficient blood, is recircu-lated through the filter, and 40 ~1./min, or 40~, is returned to the donor.
In performing a normal batch-mode procedure blood frac-tionation apparatus 20 op~xates in alternat~ draw ~nd return cycles.
During e~ch draw cycle inlet pump 32 operates to draw whole blood through the phlebotomy needle into eonduit 27 and to advance the whole blood through tubing 30 and mixing chamber 31 to filter 33.
After a predetermined voluma of plasma-defieient whole blood has been pumped through filter 33 in~o reservoir 44, the draw cycle is terminated and the return cyele is initi~t~d. Return pu~p 46 then operates to p~p plasm~-deficient blood ~rom reservoir 44 into con-duit 30 at T-fitting 28. Depending on the ~ tive operating speea of return pu~p 46 and inlet pump 32, ~ user-selectable portion Or the plasma-de~icient wh~le blood i8 pu~p~d into m~xing chamber 31 ~or subsequent recirculation through filter 33, ~nd the rem~ining portion is r~turned to the donor through donor tubing segment 27 ~nd needle 26. Upon the volume of the plasma-deficient blovd in reser-voir 44 reaehing a prede~ermined minimu~ level, th~ return cycle is terminated and the draw cycle iB again initiated. The cycles con tinue in ~lternation until a de~ired qu~ntlty of blvod has been pro-ces ed or ~ de~ired quanti$y of pl~8~ ha~ he~n collected.
Th~ blood ~r~ctionation app3ratu~ 20 i~, in further accord with the invention, conditioned between tfi~ draw cycle and the return cyele by ~ eircu$t re~ponsive to th~ weight of the r~

intermediate in-process fluid reservoir 44. To this end, the blood ~ractionation apparatus 20 includes a weight transd~cer unit 100 from which the re~ervoir container 44 i9 suspended. As shown in Figure 4, the w~ight trDnsduc~r unit 100 may include a housing 101 mounted by clamps 102 or other appropriat~ ~eans to the horizontal support bar 24 of the npparatus. Within hou~ing 101 reservoir 44 is suspended from the sen~e pin 103 of an electrical weight trans-ducer 103, which may be conventional in construction and operation, provides an electrical output ~ignal which is conveyed to the apparatus housing 21 through a connecting cable ln6.
Within housing 21, blood ~ractionation apparatus 20 in-clude~ a ~ode control circuit 107 (Figure 2) which proYides, in accordance ~ith the magnitude of the ~igDal ~ro~ weight tr~ns-ducer 100, a pair of mod2 control ~ignals fro application to ~Dtor control ~ircuiSs 72, 78 and 80 by w~y of ~ ~ontrol line 10~a and 108b. A ~od~ select switch 109, located on control p~n21 55 (Figure 3), i9 provided to ~n~ble the user to selectively disable mode con~rol circuit 107 when it is desired to operate the plasm~-phereqis appar~tus as a contlnuously running ~yste~, as in con-junction with a con~.inuous-~low two n~dl~ in ~ivo blood ~raction-ation procedure.
~eferring to Figur~ 5, within the weight transducer unit 100 the weight transdu~r 10~ s~en to cu~pris~ ~ strain gauge bridg2 circu~ 112. One input Ser~inal of network 112 is . ~ , ~: ~

~Z~:~2~7 co~nected to a source of positive current through a series-connected transistor 113, and the o~her input terminal is connected to ground.
The conduction level of transistor 113, and henc0 the voltage applied to network 112, i5 controlled by a differential amplifier 115 having its non-inverting input connected to a source of regu-lated voltage, and its inverring input connected to a voltage di-vider comprising resistors 114a and 114b. The output of dif~eren-tial amplifier 115 is connected to the base of tr~nslstor 113 through a resistor 116, with the re~ult that the voltag~ applied to network 112 iB held const~nt at all times.
The output o~ bridgo circuit 112, which depends on the force exerted on sense pin 103, is applied to a dif~erential am-plifier 120 included in ~ode Gontrol circuit 107. A neces3ary offset i5 intxoduced to this signal by an ad~u~table volt~ge divider ne~work comprising re3isto ~ 121, 122, 123 nnd 124 con-nected between the regulated input ter~in~l of network 112 and ground and the non-inverting input o4 dif~erentl~l amplifier 120.
To establish pr~deter~ined minimum ~nd ~axi~um volume thresholds for the plas~a-~e~icient whole blood in reservoir 44 the output of di~ferential ~mplifi~r 120 i9 applied to the non-inverting inpst of a comparatDr ampli~ies 125 ~d to th~ inverting input of a comparator 126. The invert~ng input o~ amplifie 125 is connected to A voltage divider comprising a r~sistQr 127 and a potentiometer 128 connect~d ~etween a sourcc o~ regulated volt-age and ground, ,~n~ the inv~rting input. Depending on the sstting ~ .

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of potentiometer 128, comparator a~plifier 125 prod~ces a logic high output si~al ~9 the volume of whol~ blood reache3 a pre-determined maximum level within reservoir 44. This output ~ignal i~ applied to the ~et input of ~n RS-typs flip-~lop 130 which pro-vides ~t its Q output the draw and retu.rn cycle mode control ~ignal.
Th~ non-inverting input of comparator amplifier 126 re-ceives a reference voltage dev~loped by a voltage divider compri-sing a r~sistor 131 and a pot~ntio~.eter 132. Depending on the setting of potentiometer 132, the threshold of comparator ampli-fier 126 is varied to establish the mini~um threshold level. Com-parator 126 produces a logic low output which is applied to the reset input of flip-flop 130. Re3istor~ 133 ~nd 134 supply neces-sary operating current to the outputs of compar~tor a~plifiers 125 and 126.
To enable blood ~ractsonation apparatus 20 to be used for a continuous flow procedure wherein the ACD, inlet and retusn pu~ps are continuously controlled by controls 60a, 61a and 63a, respec-tively, a~ AND gate 136 is connected between th~ Q output o~ fl}p-flcp 130 and coDtrol line 10~a, and Rn OR ~ate 137 is connected b~-tween the Q output and control line 108b. One input of gate 136 is connectea to a po5itiv2 currsnt sour e by a r~sistor 13a, and to ground by ~sdc switch 109. Gate 129 i~ si~ilarly connected through ~n inv~rter 139. When switch 10g i~ open, c~rre~ponding to oper~tor selection of a con~inuous- low pro~ed~re, AND gat~ 736 is inhibited, rendering control line 108a logic low ~nd con~rol line lD8b logic high, c~using th~ pumps ~o operate continuously under the controls o~ 60a, 61a and ,~

63~. ~owever, when swi~ch 109 is c103~d, ~ND gate 136 is enabled and the logic state of control line 10!3 is dependent un the oper-ating 3tate of RS flip-flop 130, and hence the volume of plasma-deficient blood accumulated in r~ervoir 44.
Referring to Figu~e 6a,the motor control circuit 72 provided for supplying operating power to the inlet pump moto~
70 comprises a seri~s-connected power transistor 140 and a reac-tance control network comprising an inductance 141 ~nd a capaci-tor 142. ~hese components ~upply power from a unidir~ctional motor current source ~not shown) to the motor. The r~turn line from the tor includes a serie~-connected current ~ætering re-sistor 143.
Pump tor 70 is a direct current type motor and re-ceive~ excitation ove~ a variable duty cycle through power tran-sistor 140. Conduction o~ this transistor iB controlled by a pulsz width modulato~ 144 wbioh ps~vide an appropriate control signal t~ the ba3e electrode of the transistor. A tachomete~
formed by a light emutting diode 145 and ~ photod2tector 146 operates in ~ conventional manner to provide output pulses indi-cative of increment~l rotation of the pump motor. ~hese pulsei are ~pplied to a t~chometer output line through an ~mplifier 147 for use by other ~ystems within the appAratu~, 3nd through an ampli~ier 14B to a freu~ency~to-voltag~ convert~r c~rcuit 149.
This circuit develops ~n analog output voltag~ in proportion to the freguency of the tachometer pulses. ~hi~ nignal is ~pplied ~ `

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to the inverting input of a ~omparator amplifier 150, wherein it is compared with a speed control signal applied to the non-inver-ting input from potentiom~ter 61a or 61b thr~ugh a trio of a~alog devices 151-153.
s The control gate of swit~h de~ice 151 ~9 connected to the pump control line 82 so that in the absence o~ an appropriate motor enabling signal from the apparatus control circuit ~1 no reference ~ignal is applied to comparator 150. The control gAte of switch device 152 i~ connected to mode control line 108a through an inverter 154 so th~t in the absenc~ of a logic high signal on this control lin~ ~n an~log control signal m~y be applied to com-parator 150 by the draw mode whole blood rate control potentio-meter 61a. ~he control gate of ~witch device 153 is conne~ted dire~tly to mods control li~e 108, so that in the presence of a logic high signal on this line ~he outpu~ of the return rate potentiometex 61b ~ applied to compar~tor 150.
Comparator ~mpli~ier 1S3 operates in ~ conventional manner to produce an output ~ignal indicativ~ of th~ difPerence between its inpu~s. ~his autput sign~l iq applie~ through an isolatlon cir~uit 155 to pul e width modul~toY 144, wherei~ it control~ the du~y cycle o~ power transistor 140, and hence the speed of pump mstor 70.
Re~erring to Fi~ure 6b, tb~ return pump motor control circuit 78 ~ay be idantical to motor co~trol d rouit ~2, except for the input circuit provided Por potentiometer r~te controls .

~6~Z~7 63a and 63b and control line 108b.
~o p~ovide protection against overspeed oper~tion, the ~cit~tion level applied ~o pump ~otor 70 i~ continuously monitored by an overspe~d detection clrcuit 156. In the event of an ovsrspeed condition, this circuit provides ~n o~tput which i5 coupled through an OR gate 157 to the alarm output line 84, and to the inhibit input of pul5e wiclth modulator 144, wherein it prevent~ the application of current to the ba~a o~ transistor 140, thereby stopping the motor. Addition~l proteetion ag~inst malfunction i9 provided by a stall detectio~ circuit 158 which provides an input to 0~ gate 156 upon motor 70 becomi~g stalled, as detected by the voltage level acros~ serieQ-connected resis-tor 143.
Referring to Pigure 7, a multi-phas~ drive ~ignal is applied to the antioo~gulant pu~p ~tepp~x ~otor 79 by a r4t~pper motor drive CirGUit 160 of conventional design. Control pul~es for initiating the multi-phase drive signal from dri~c circuit 160, and consequently each increment~l rotatio~ o~ the ~otor, are provided by a clock circuit 161. In the draw moae, output pulses from the clock are applied through ~ pair of ~nalog switch deYic~s 162 ~d 163 to a rate ~ultiplier 164. Rate multipl$er 164, whieh may be conventional in constructlon and op~ration, respon~s to an operator-selectee r~te set by switch 60a to provide a pre-~.~

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selected r~te multiplication to the applied clock pulses. ~his results in stepper motor drive circuit: 160 being impulsed at a user-selected rate, and consequently the stepper motor 79 being driven ~t the desired rate.
Alternatively, clock pulses from cloc~ 161 are supplied to a second rate multiplier 165 through switch device 162 and a third analog switch device 166. nhen devices 162 and 166 are conductive, rate multiplier 165 is active to control motor speed according to ~he setting of return mode rate selector switch 60b.
Control over operation of stepper motor 79 is obtained ~y apparatus control circuit 81 by applying tha pump enable con-trol signal developed on control lins 82 to analog switch device 162. During batch de operation of the blood fractionation apparatus, analog switch de~ice 162 is enabled continuously.
Switch device 163, which is conn~cted to mode control line 108 through an inverter 167, is en~bled during each draw cycle to render switch 6OA operative. Switch device 166, which is connected directly to control line 10Ba, is conductive only during each return cycle. Consequently, switch 60b controls return rate.
In a non-recirculation procedur~, contxol line 108a provides a continuous logic low signal and only rate mult~plier 164 and switch 60a ~re utilized. Th~ output~ of rate ~ultipliers 164 and 165 are applied $o stepper mo~or drive oircuit 160 and a stall detection circuit 168 through an OR gate 169.
The anticoagulant pump drive circuit 80 also includes ~ .

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, ' ~Z~;~2~1L7 a tachometer ~omprising a light emitting diode 170, a slotted disk 171 and a photodetector 172. A~ dis~ 171 turns with motor 79, output pulses produced by photodet~ctor 172 are supplied through a first inverter ~mplifier 173 to ~ tach output line. Puls~s are S also supplied through ~ second inverter amplifler 17~ to stall detector lS8, which provides an output on alarm line 94 upon stepper motor 79 stalling.
The operation o~ blood fractionation sy~tem ~0 is illus trated in Figures 8a-8d and 9. In thc batch ~ode, the system operate~ a~ illustrat~d in Figures 8a and 8b. Where no r~circu-lation through the ilter i9 de~ired in the batch mode, the sy~tem operat~s as illustrated in Figures Ba and 8c.. Where the system is to be pri~ed, the system operate~ ~s illustrated in Flg~re 8d.
During the ~raw ~yole, ~8 shown in ~igure 8a, whole blood is drawn from ~ donor through a single-lumen phleboto~y needle 26 and the bidirectionnl donor interf~ce conduit 27 by inlet pump 32, which pump8 the whole blood along conduit segment 30 to mixing chamber 31. Wi~hin the ~ix~ng ch~mbex, the ~xeshly drawn whole blood is, in accordance with one a3pe~t o~ the invention, mixed with whol~ blood previously advauced along segment 30 by pu~p 32, and the resul~in~ mixture is advanced through filter 33 to reser voir 44, As the ~ixed whole blood fro~ chamb~r 31 pas~es thrvugh filter 33, a portion o~ the plasm~ component oon~ained ther~in i~
~S

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separated from -the whole blood by the membrane element of 'che filter and is caused to flow through tubing segment 41 to plasma collection container 42. 1'he volume of plasma thus collected can be readily S determined by reference to a conventional weight scale 180 from which the plasma collection container is suspended. Alternatively, a collected volume monitoring system such as that described in U.S. Patent No.
4,458,539 of Arnold C. Bilstad et al, entitled "Blood Fractionation Apparatus Having Collected Volume Monitoring System" may be utilized to provide a direct readout of collected plasma volume.
During the draw cycle the operating rate of the inlet pump 32 is set by potentiometer 61a. The lS operating rate of the return pump 46, which is normally not operative during the draw cycle, may be set to zero by setting potentiometer 63a to zero. As an alternative, to preclude operation of the return pump 46 during the draw cycle, potentiometer 63a may be eliminated in the replacement pump motor control circuit 78 and the input to analog switch device 152 in that circuit may be connected to ground, as shown in Figure 6b. The operating rate of ACD pump 40 is set by selector switch 60a to operate a rate appropriate to the operating rate of inlet pump 32 to maintain a desired ratio of ACD to whole blood.
The plasma-deficient whole blood from the filter continues to collect in reservoir 44 during the draw cycle. As the weight of the whole blood in the reservoir increases, transducer .

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~Zt~ 7 100 produ~es a progressively increa~ing output signal. When this signal reaches ~ level corresponding to fluid l~vel 11, in ~eser-voir 44, the signal applied to comparator 125 (Figure 5) by differential ampli~ier 120 causes comparator 125 to produc~ an S output signal which condition~ RS flip-.Zlop 30 to its set statç.
As a consequence, the Q output o~ flip-:~lop 130 beeo~es logic high, ænd, assuming AND gate 136 i5 ena~led by mode switch 109 being open for bstch operation, mode comtrol line 108a con~eys a logic high control signal. Thi~ causes termination of the draw cycle and initintion of the return cycle.
During tha return cycle, as illustrated in Figure ~b, return pump 46 is operated to pump plas~-de~icient ~hole blood from reservoir 44 back through conduit s~gment 45 to donor conduit 27 and conduit seg~ent 30 ~t T-connector 28. ~he flow rat~ of the plasm~-d~ficient whole blood, as e3t~bli~hed by return pump 46, under the control of pot~ntio~eter 63b, i3 ~t higher than the flow rate of th~ whol~ blood in conduit segment 30, as established by inlet pump 32 under ~he control of potentiometer 61b. As a result, the plasma-deficient whole blood flowing rom reservoir 44 i3 cau~ed to div~de between donor onduit 27, wherein it c~uses a flcw revers~l and ~low in~o the donor through the lumen of thc single-lumen phleboto~y needle, and conduit ~eg~en~ 30, wherein it is advanced townrd ~i~ing ~h~bes 31 ~nd f~lt~r 33.
Within mixing ~h~mber 31 the recirGula~ing porti~n o~

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the pla~ma-deficlent whole blood divided into conduit ~egment 30 is caused to mix with whole blood previously pumped int~ the chamber, as duri~q the previous draw cycle of th~ system. The resulting ~ixture, which ha~ a hematocrit deter~n~d by the he~a-tocrits of the recirculating plasm~-deficient whole blood and the prevlou~ly pumped resident whole blood, is advanced through filter 33 into reservoir 44 by inlet pump 32. Thi~ cause~ an additional qua~tity of pla~ma to be separated fro~ the whole blood mixture by filter 33 and stored in plasma container ~2.
The ratio o~ plas~a-de~icient whole blvod returned to the donor to plas~a-defici~nt whole blood recirculated through filter 33 is dependent on the relative operating rates of the inlet pump 32 ~nd the r~turn pu~p ~6. Por a relativ01y higher ~etusn. . pu~p r~te, a high~r percent~g~ o~ plasma-deficient whole blood ~ 5 returned to ~h2 ~onor. The actual sper~ting rates of tha i~let hnd r~tuFn pu~p~ d~rins the return cycle are set by the oper~tor by ~ean~ of potentiometcrs 61b and 63b on panel 55. In practioe, the~ ratec are li~lted by practical con-sideration~, 3uch a~ the flow rate and pr~s ure requ$rement~ of ~0 filter 33, the maximu~ per~i~sible dr~w and return rate~ o~ the donor, ~nd th~ c~pDcity of the condu~t ~gmant~ 2nd ~s~ociated system component~. The ACD pu~p ~O n~y be operated during the return cycl~ ~ a ra~ ~el~ct~d by selector swl~dh 60b to m~intain a de~ire~ percentage o~ AC~ ~olu~ion ~n the i~-proc~ whole blood.
Oper~tion in th~ ret~rn cycle continue~ un~ he ~olume - ~7 -, 2~7 of plasma-deficient whole blood in fluid re~ervoir 44 reaches a predetermined minimum level, corresporlding to levPl 12 in Pigure 8b. At ~his time the output sig~al produced by weight transducer 100 causes comparator 126 (Figure 5) to toggle R3 ~lip- lop 130 to its re~et state, causing a logic low on ~ode control lines 108a and 108b. This c~uses ~nalog ~witch de~ic:es 152 ~Figures 6a and 6b)and 163 ~Pigure ~) to close and analog ~wi.tch de~ices 153 and 166 to open, thereby enabling the lnlet pump dr~w cycle potentiometer 61a (and repl~cem~nt pump draw cycle potentio~eter 63a in a ~imilar manner) and the ACD dr~w cycle rate selector ~witch 60a. Conse-guently, the retur~ cycl~ iq termin~ted and a new draw cycle i5 i"itiat~a.
Referring to Figure 9, auring altern~te draw and return cycles of blood fractionatlon syqt~m 20 the volume 181 o~ plasma-deficient blood in re~rvoir 44 i3 seen to vary betwe~n a pre-determined ~d~imu~ l~vel, correspondiDg to level 11, and a pre- -determined mini~u~ level, corresponding to le~el 12. ~t the same time, the volume 183 o~ plasma coll~eted in container ~2 is seen to incre~se with each cycle, at a ~aster rate during draw cycle~
~s ~reshly drawn blood is ~ilterea, and ~t a ~lower r~te duri~g return cycle , a9 recircul~ted blood i~ filter~d with previou~ly dr~wn bl~d. Norm~lly, the ~rac~$o~ation procedur~ i~ continued until a desired volu~e of plas~a (or oth~r deslr~a bloo~ ~raction) has been collected, as determined by the w~igh~ o the collected pl~s~a ~B r~ad on scal~ 180.
a result o~ the parti~l reci~culation o~ plasma-d~-- 2~ ~

ficient whole blood from re3ervoir 44 during each return cy~le, the system filte~ oper~te~ during both draw and ~eturn cyal~s and the time required Por s~parating a g:iven volume of plas~ta i5 significantly reduced.
For exampl~, th~ eff~t of recircul~tion through the filter ~or a system yield of 600 ml. plasma, a donor of 5000 ml.
whole blood, ~ 200 ml./min. return pump rate, ~ ~ixing chamber volume of 30 ml., and an in-process ~luid reservoir having a predetermlned maxi~um voluma of 50 ml. and a pred~ter~ine~ mini-mum volume of 30 ml., can be sun~trrized for v~y$ng whole blood he~atocrits ~nd flow rates as follow~:
NO ~ECIRCUL~TION ~I~ RECIRCULAT~ON
olo ~losd Donor Proc~d- Blood~Sax Fllt~r Proc~d- 13100d Ibx Pllter Flo~ Rae~ 'Slmo Proce-- 8e~tocrit ur~ S~ Proc~ anat~erit ~mlh~n) c~:lt t~) ~min) J~d ~mt ) ~ in~ ~ed ~
44.51690 4139.7 1520 4B
SO 45 40.51~31 4642.9 1631 53 50 53 . 21990 5146 . 7 1765 58 58. 52178 ~651 . 3 1923 62 39.61667 4134.0 1454 48 42.glB02 4636.6 1555 54 ~6.8lg5a 5139.9 1686 58 51~52138 5643.6 1~35 63 40 36 . 5169q 4130 . 5 1451 51 ~O 45 39.51826 4633.1 1556 56 50 93 . 219~5 5135 . 9 1664 62 4~.a21a3 5639.3 1~20 66 Thus, ~or hematocr~t~ w~thin the norm~lly encountered range of 40-55~ th~ ~ingle-lumen ~ingle needlQ p~rtial-eecircula-tion blood ~ractionation ~yste~ of the prese~t in~entlon requires less processin~ time and le ~ whol~ blood th~n a non-recl~cul~tiion , .

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~Z~ 7 singlP-lumen single ne~dle b~tch systi!m wherein whole blood is draw~, filtered and returned in di~cr~te batches and no recircu-lation through the filte~ takes place. Only th~ mor~ complex and le~s convenient two needle continuous flow ~tems, which ~equires two phlebotomy needles, has a greater sy~tem e~iciency.
This is illustrated in Figure 10, wherein collected plasma volumes 183, 184 and 185 are depicted for two needle continuous, single needle recirculation and single needl~ b~tch ~y~tems, ~espec-tively.
Wher~ it i~ desired to operat& the ~lood ~ra~tionation system without r~circulation, as where a donor i5 encountsred having ~n unusually high hematocrit which rai~e3 th~ probabili~y o~ he~olysis in a ~econd pa~ ~hrough the ~ilter, the operating speed of the inlet pump during the retur~ cycl~ can be set to zero by mean~ o~ potentio~eter 61b. Then, a~ shown in Figure 8c, all of the plasma deficient whole ~lood pu~ped fso~ reservoir 44 during th~ return cycle i~ cnused to flow ba~k to the donor through the donox interface conduit 27 and the ~ingle lumen phle-botomy needle 26. Inlet pu~p 32, being motlonle~ unotions A~
a valvo to prqYent flow through tubing segment 30, thersby ob-viating ~he need for ~eparate fluid ~low cont-ol v~lve~ and their attendant ~ontrol sy~tem~.
Wher~ e~ception~lly lo~ hematocrit~ ar~ ~ncountered, subs~anti~lly all of the pl~sm~ deficient whol~ blood fro~ re~er-voir 44 can be ~ecir~lated thsoug~ filter 33 by ~etting the inlet .

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~2~ 7 pump 32 and the replacement pump 46 to operate at the same rate.
It is contempl~ted that this proc~dure would be used only for short time perlods, such as required to complete a second pass through the filter, ~o avoid 3ubjecting the filter to exsessively high hematocrits and ~ttendant hemoly6is.
During ~he draw 3nd return cycles the ACD pump 40 in-troduces ACD ~olution into conduit ~egmlsnt 30 at respective rates selected by the operator. The operstion of the ~CD pump and the rate selected are options available to the phy~ician and may vary according to the particul~rs of the psocedur~.
Prior to initial operation o~ the blood fractionation system a prime mode may be provided wherein air i~ removed from the conduit segment~ and fluid path element~ of the system. As shown in Figure ~d, the saline lin~Y Sl and 53, heretofore clamped closed during the drawn and return cycl~, are opened.
The donor conduit segm~nt 27 is clampad shut and pump5 32, ~0 and 46 are operated to pump saline ~olution frc~ container 52 and ACD ~olution ~rom continer 36 thsoughout the syste~. ~rapped ais and bubbles are forced into ~he combined bubble trap and fluid abs~nc~ dete tor 47, wherei~ they are collected and dis-charged through line 53 to saline cont~iner 52. Fluid absence detector 47 i8 disabled and the procedure continue~ until all trapped air has be~n ~xh~u~ted. She procedure ;~ then terminated by the opcrator, and after the ~y~t~m has been sonnected to the donor, an appropriat~ input i~ applied to control circuit 81 to '~ .' . :

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~2~,~Z~7 initi~te a draw cycle.
Thus, the blood ~ractionatio~ qy3tem o~ the invention c~n be conveniently 5et Up, and once in use c~n operate auto-matically without continuous operator intervention. By reason of it~ increased plas~a 3ep~r~tion efficiency, the ~ystem of the invention can utilize a smaller volume filter component and hence a smaller volume flow syst2m, to accomplich a qiven blood frac-tionation proc~dure. Since the smaller filter requires a smaller microporous filter element, the co~t o~ ths filter component, and hence the cost of th~ system, is reduced.
The fluid flow system 25 utilized iD conjun~tion with the system may be ~or~ed o~ vinyl and other plnstic non-pyrogenic mRterials as a single use disposable flow set, as ~hown in ~igure 11. The ~et is preferably individually packaged in a sterile condition for convenient long ter~ storage prior to use.
The muxing c~mbzr 31 i~ provided up-line of filt~r 33 to mix the plasm~-defi~ient whol~ blood di~erted for recirc~lation with previously drawn whol~ blood, ther~by aYeraging the hemato-crit of whole blood circulating through the filter over ~ucce~sive draw and return cycles and ~nabling the flow rate and pressur~
~t th~ ilter to be mor~ nearly optlmized. ~o thi~ ~nd, the mixing chambes pre~erably has a ~olume substanti~lly equ~l to or greater th~n the volume of plasm~-deficiant whol- bloDd pumped from re-ser~oir 44 during the return cycle. Thi~ aCsure~ th~t the ~e-circulat~d plasma-de~icient blood will mi~ wi~h a~ le~st an egual ~ .`

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::' volume of prevlously pumped blood. In practice the mixing chamber may have a volume which is a multiple of the volume pumped from the in-process chamber. For example, in one successful application of the invention, which utilized an intermediate fluid reservoir having a volume of 100 ml., a high lin~it of 50 ml., and a low limit of 30 ml., a mixing chamber having a volume of 50 ml. was provided in conjunction with a filter having a 5 ml. volume. In this application, a return pump speed of 200 ml/min, was utilized in conjunction with inlet pump speeds of 50-70 ml./min. This provided a ratio of 3:1 between the pump speeds, which has been found to provide good efficiency with the 40-55~ hemocrit levels typically encountered, as shown in the previous tabulation.
While the use of a weight-responsive transducer has been shown for controlling the return cycle, it is possible to use other control means, such as electrical switches actuated by a mechanical weight scale linkage on which reservoir 44 is supported, or a pair of ultrasonic level detectors arranged to sense blood level in the reservoir. Also, the system may be used in conjunction with a pressure cuff, as described in U.S.
Patent No. 4,498,983 of Arnold C. Bilstad et al., "Single Needle Blood Fractionation ~ystem Having Pressure Cuff Draw Mode Enhancement".
The blood processing system of the invention has the further advantage of being dependent only on the volume of separated cellular component, or plasma-deficient whole blood, which ~.

: .

Z~7 is directly related to the volume of whole blood processed; and not on the volume of the collected non-cellular component, or plasma, which is dependent on the hem~tocrit o~ the whole blood nnd therefore not directly related to processed volume. This enables the system to draw and return without re~djustment batches of uniform volume from different donors, notwithstanding difer-ences in hematocrits between the donors.
While the invention has been shown in conjunction with a hollow fiber type filter, it will be appreciated that it can be utilized in conjunction with other types of filters, such as a flat membrane type filter, or a centrifugal separator. Also, in conjunction with the hDllow fiber me~brane filter shown, a pressure regulator valve and TMP monitoring system m3y be em-ployed ~or more ~ccurate T~P control.
While n particular embodiMent of the invention has been shown and desc~ibsd, it will be obvious to those skilled in the srt that cnanges and modifications may be ~ade therein with-out departing from th~ invention in its broader aspects, and, therefore, the aim in the ~ppended cl~ims is to cover all such ch~nges and modifications ~s fall within the true spirit and scope o~ the invention.

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Claims

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

1. A single needle blood fractionation system for separating a blood fraction from whole blood, comprising:
means including a donor interface conduit adapted for connection to a phlebotomy needle and alternately operable in forward and reverse flow for alternately receiving and returning blood from a donor;
an intermediate fluid reservoir;
means including a first: conduit connecting said donor conduit to said intermediate fluid reservoir;
means including a flow-through filter disposed in said first conduit for separating the desired blood fraction from whole blood flowing through said filter;
means including a second conduit connecting said intermediate fluid reservoir and said donor interface conduit;
an inlet pump for pumping fluid through said first conduit to said reservoir;
a return pump for pumping fluid from said intermediate reservoir through said second conduit;
system control means responsive to the volume of fluid in said intermediate reservoir for initiating operation of said return pump in response to said volume reaching a predetermined maximum level, and for terminating operation of said return pump upon said volume reaching a predetermined minimum level; and the rate of said return pump being adjustable relative to the rate of said inlet pump whereby upon operation of said return pump an operator selectable portion of the filtered blood in said second conduit is caused to recirculate through said first conduit and said filter.

2. A blood fractionation system as defined in claim 1 wherein said system control means are responsive to the weight of said intermediate reservoir.

3. A blood fractionation system as defined in claim 2 wherein said system control means include an electrical weight transducer providing an output signal indicative of the weight of said reservoir.

4. A blood fractionation system as defined in claim 3 wherein said output signal is an analog signal, and said system control means include means for comparing said output signal with predetermined maximum and minimum reference levels.

5. A blood fractionation system as defined in claim 1 wherein the rates of said inlet and return pumps are operator-adjustable.

6. A blood fractionation system as defined in claim 1 wherein said inlet and return pumps are each peristaltic-type pumps.

7. A blood fractionation system as defined in claim 1 wherein said filter is a membrane type filter.

8. A blood fractionation system as defined in claim 7 wherein said filter is a hollow fiber type filter.

9. A blood fractionation system as defined in claim 1 wherein said second fluid conduit means include a bubble trap and a fluid absence detector.

10. A blood fractionation system as defined in claim 1 wherein said separated blood fraction comprises plasma.

11. A blood fractionation apparatus as defined in claim 1 wherein said inlet pump and said return pump each comprise positive displacement pumps.

12. The method of separating a blood component from whole blood, utilizing a phlebotomy needle, and flow-through separating means, comprising the steps of:
pumping in whole blood drawn through the needle through the separation means;
collecting the component-deficient blood from the separation means in a reservoir;
initiating pumping back component-deficient blood from the reservoir to the needle upon the volume of blood in the reservoir rising above a predetermined level;
said pumping back being at a higher rate than said pumping in whereby the volume of blood in the reservoir is caused to diminish; and terminating pumping back from said reservoir upon the volume in the reservoir falling below a predetermined minimum level.

13. A blood fractionation system as defined in claim 1 and further including means for defining an inline mixing chamber disposed in said first conduit between said donor interface conduit and said flow-through filter, said chamber having a volume substantially equal to or greater than said volume of the fraction-depleted blood component intermittently pumped from said intermediate reservoir to mix said second portion of fraction-depleted blood component recirculated through said first conduit with a portion of whole blood advanced through said first conduit prior to initiating operation of said return pump.

14. A method as defined in claim 12 and further including the step of mixing, prior to its recirculation through the separation means, the second portion of the intermittently pumped volume of the fraction-depleted blood component with a quantity of whole blood drawn from the donor which is substantially equal to or greater in volume than the total volume of the fraction-depleted blood component pumped from the reservoir during said pumping back step.