WO1983002059A1

WO1983002059A1 - Blood fractionation apparatus

Info

Publication number: WO1983002059A1
Application number: PCT/US1982/001641
Authority: WO
Inventors: Inc. Baxter Travenol Laboratories; Arnold C. Bilstad; John T. Foley
Original assignee: Baxter Travenol Lab
Priority date: 1981-12-15
Filing date: 1982-11-19
Publication date: 1983-06-23
Also published as: JPS59500083A; DK371783D0; IT1155223B; BR8208017A; ES8405634A1; DK371783A; IT8224749A0; EP0096693A4; AU1045383A; EP0096693A1; ES518245A0

Abstract

An apparatus for separating and collecting plasma from whole blood includes volume and rate monitoring systems (92, 93) which provide continuous automatic displays of the volume and rate of plasma collected. The systems analyze incremental changes in the collected plasma weight over successive time intervals. The systems continuously display volume and rate measurements, and are not effected by changes in tare weight or a change in the plasma collection container. The apparatus further includes a ratio control system (106) which enables replacement fluid to be added by a replacement fluid pump (52) associated with the apparatus to process plasma-deficient blood at a predetermined ratio relative to the volume of plasma collected in a collection container.

Description

BLOOD FRACTIONATION APPARATUS

FIELD OF THE INVENTION

The present invention relates generally to apparatus for processing whole blood, and more specifically to blood fractionation apparatus for separating and collecting a desired blood component, such as plasma.

BACKGROUND AND OBJECTS OF THE INVENTION

Various methods and apparatus have been developed for the continuous flow processing of whole blood, wherein whole blood is taken from a live donor, a desired blood component is separated and collected, a replacement fluid is added to the processed blood, and the processed blood is returned to the donor. Blood components typically collected using such processing include plasma (plasmapheresis), white blood cells (leukopheresis) and platelets (plateletpheresis).

Continuous flow blood processing apparatus may be of the centrifugal type, wherein the differing density of the collected blood component causes the component to congregate for collection at a particular radial distance in a centrifuge, or may be of the filter type, wherein the particle size of the collected component allows only that component to pass through a filter membrane into a collection^~ chamber. Filter type apparatus is generally preferable for continuous flow plasmapheresis applications, since such apparatus does not require complex rotating machinery and is more compact and less costly to manufacture. One form 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

OMFI 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 bag. A preferred construction and method of manufacture of such a hollow fiber filter is shown in the copending application of Robert Lee and William J. Schnell, entitled, "Microporous Hollow Fiber Membrane Assembly and its Method of Manufacture", Serial No. 278,913, filed June 29, 1981. To preclude the collection of too much of one blood component, such as plasma, from a donor, and consequent danger to the donor's health, it is highly desirable that the volume and collection rate of the blood component collected be monitored and maintained within prescribed limits. Preferably, the volume of the component actually collected and the actual rate of plasma collection should at all times be displayed in a digital form clearly readable by the operator. Prior art plasmapheresis apparatus relied on the weight of the plasma collection container to provide indications of collected plasma volume and plasma collection rate. One such apparatus is shown and described in the copending application of Arnold C. Bilstad and John T. Foley, entitled, "Apparatus and Method for Weighing Material Being Collected", Serial No. 140,111, filed April 14, 1980.

One drawback of such prior-art weight-based systems has been the necessity of making mathematical calculations to determine collected volume and

O FI collection rate. Furthermore, it has been necessary to initially obtain the tare weight of the collection container prior to each collection procedure. Moreover, with such systems it has been necessary to reinitiate the collected volume and rate measurement procedure with each change of collection container. This is not only time consuming, but also introduces a potential for error in the volume and rate determinations. The present invention overcomes these drawbacks by providing a system which automatically determines and displays the volume and collection rate of a blood fraction collected by analyzing incremental changes in collected plasma weight over successive time intervals. The volume collected and rate of collection is continuously displayed, without consideration of changes in tare weights or changing of the plasma collection container.

In plasmapheresis procedures it is frequently desirable that a replacement fluid be introduced into the processed plasma-deficient blood to replace the collected plasma prior to returning the processed blood to the donor. In this exchange procedure the replacement fluid is typically introduced by a replacement pump at a fixed volume ratio to the collected plasma, as specified by the attending physician.

In prior art filter-type plasmapheresis systems the speed of the replacement pump, and hence the replacement fluid rate, was manually set by the operator, after observing the plasma collection rate and mathematically calculating the necessary replacement rate from the specified replacement ratio. For each change in collection rate is was necessary to manually reset the replacement rate, and failure to note a change in collection rate resulted in an improper replacement rate.

The present invention overcomes these drawbacks by providing a system which automatically proportions the volume of replacement fluid added to the volume of plasma actually collected according to an operator-set ratio. The system includes an autologous mode, wherein plasma is withdrawn from the collection container for treatment and return to the donor by the replacement pump at a rate which is automatically set to maintain a constant volume of collected plasma in the collection container.

Summary of the Invention

The invention is directed to apparatus for monitoring fluid flow^"into and out of a container, such as the plasma collection container of a plasmapheresis system. The apparatus includes circuit means including an electrical transducer for providing a signal having a frequency related to the weight of the container and the fluid contained therein, and derivation means for deriving from this signal an collection signal indicative of incremental units of volume collected in the container. The invention is further directed to the apparatus as described above, wherein the derivation means includes a counter responsive to the collection signals for providing a cumulative count of units of volume collected, and incrementing means for applying only those collection signals to the counter which do not exceed the maximum collection capability of the system to develop an output indicative of total volume collecte . The invention is further directed to the apparatus as described above, wherein the derivation means include means for periodically comparing the frequency of the transducer output signal over a measurement interval with the frequency of the signal over a preceding measurement interval to develop difference signals each indicative of increments of volume collected during the measurement interval. The invention is further directed to the method for monitoring fluid flow into and out of a container, such as the plasma collection chamber of a plasmapheresis system,^' wherein a variable frequency signal is provided by, a transducer according to the weight of the collection container and the collected fluid, and is compared over successive measurement intervals to develop an output signal indicative of incremental units of volume collected.

The invention is further directed to the method described above, wherein those output signals which do not exceed the maximum collection capability of the system are accumulated in a counter to provide 5 an indication of total volume collected.

The invention is further directed to apparatus as described above wherein accumulator means are provided for accumulating a predetermined number of the most recent of the collection signals

10 corresponding to a desired time unit and display circuit means for providing a rate-indicative output signal in reponse to the sum of the collection signals in the accumulator.

The invention is further directed to a method of

15. determining the rate of collection of a fluid, such as plasma, incrementally added to a container, as in a plasmapheresis apparatus, from periodic collection signals indicative of increments of fluid added to the container. The method includes summing the most

20 recent of the collection signals over a unit of time, and displaying .the sum as the rate of addition.

The invention is further directed, in a blood fracionation apparatus for separating and collecting a blood fraction from whole blood, and of 5 the type utilizing a flow system having a collection container for the collected component, and a motor driven replacement pump for adding replacement fluid to the fractionalized blood component, to a control system for maintaining a predetermined ratio between 0 the volume of fraction collected and the volume of

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replacement fluid added. The system includes derivation means including an electrical transducer for producing a collection signal indicative of incremental units of volume of the fraction collected and means responsive to operation of the replacement fluid pump for providing output pulses indicative of the volume of replacement fluid added. First ratio circuit responsive to the collecton signals produces a first comparison signal, and a second ratio circuit responsive to the replacement fluid output pulses produces a second comparison signal. Comparison means are provided for comparing the cumulative occurrences of the first comparison pulses with the cumulative occurrences of the second comparison pulses to develop an output signal for controlling the speed of the replacement pump motor.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of the present invention which are believed to be novel are set forth with particularity in the appended claims. The invention, together with the further objects and advantages thereof, may best be understood by reference to the following description taken in conjunction with the accompanying drawings, in the several figures of which like reference numerals identify like elements, and in which: Figure 1 is a perspective view of plasmapheresis apparatus incorporating a collected volume display system constructed in accordance with the invention. Figure 2 is a functional block diagram showing the principal components of the plasmapheresis apparatus of Figure 1.

Figure 3 is an enlarged perspective view of the overhead collection monitor and replacement rate control unit of the plasmapheresis apparatus of

Figure 1 partially broken away to show the electrical strain transducer incorporated therein.

Figure 4 is an enlarged side elevational , view partially in section of the electrical strain transducer in conjunction with a plasma collection container.

Figure 5 is a simplified schematic diagram of the circuitry utilized in conjunction with the electrical strain transducer. Figure 6 is a simplified block diagram of the collected volume display system of the plasmapheresis apparatus of Figures 1 and 2. Figure 7 is a logic table useful in understanding the operation of the collected volume display system of the plasmapheresis apparatus. Figure 8 is a depiction of certain hypothetical weight variations of the collection container with time useful in explaining the operation of the collected volume display system of Figure 6.

OMPI Figure 9 is a simplified schematic diagram of the clock circuit of the plasmapheresis apparatus of Figures 1 and 2.

Figure 10 is a depiction of certain waveforms produced by the clock circuit of Figure 9 useful in understanding the operation of the collected volume and collection rate display systems of the apparatus.

Figure 11 is a simplified schematic diagram of the collected volume display system of Figure 6.

Figure 12 is a simplified functional block diagram of the collection rate display system of the plasmapheresis system of Figures 1 and 2.

Figure 13 is a depiction of hypothetical data flow useful 'in understanding the operation of the collection rate display system of Figure 12.

Figure 14 is a simplified schematic diagram of the collection rate display system of Figure 12.

Figure 15 is a simplified functional block diagram of the fluid replacement rate control- system of the plasmapheresis^" apparatus of Figures 1 and 2 configured in an exchange mode.

Figure 16 is a tabulation of certain signals associated with the operation of the fluid replacement control system.

Figure 17 is a perspective view of the plasmapheresis apparatus of Figure 1 in conjunction with a fluid flow system for autologous mode operation. Figure 18 is a simplified functional block diagram of the fluid replacement ratio control system of Figure 15 configured with an autologous mode.

Figure 19 is a simplified schematic diagram of the fluid replacement rate control system of Figures 15 and 18.

Figure 20 is a perspective view of a collection monitor and replacement fluid pump apparatus constructed in accordance with the invention, for use in conjunction with continuous-flow blood fractionation apparatus.

Figure 21 is a functional block diagram showing the principal components of the collection monitor and replacement fluid pump apparatus of Figure 20.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to the drawings, and particularly to Figure 1, a plasmapheresis apparatus 20 incorporating the present invention is seen to include a lower table-mounted processing unit 21, and an upper rack-supported collection monitor and reinfusion rate control unit 22. The processing unit is shown mounted on a table 23 of conventional design having a generally horizontal top surface 24 on whic . the processing unit is supported. However, the processing unit may be removed as necessary from table 23 and installed on other surfaces.

OMPI The collection monitor and reinfuse control unit 22 is preferably supported on a pair of vertical support poles 25 and 26 attached to the rear wall (not shown) of the processing unit. As shown in Figure 1, the separation between the two units is preferably sufficient to allow a plurality of collection and dispensing containers of conventional construction to be hung by appropriate hangers from the bottom surface of the monitoring and control unit. Necessary electrical connections are established between the two units by means of an electrical cable 27 attached to support pole 26 by cable ties 28 or other appropriate fastening means. The processing apparatus 20 is capable of operation in an exchange mode, wherein a desired blood component, such as plasma, is removed from whole blood received from a donor and replaced at an automatically maintained volume ratio by a replacement fluid added to the processed blood prior to the processed blood being returned to the donor; or in an autologous mode, wherein the collected component is automatically removed from the collection container so as to maintain a constant volume in the container, is processed in a secondary treatment system, and is then returned to the donor. A fluid circuit for use in the exchange mode is generally identified by the reference numeral 30 in Figure 1 and shown schematically in Figure 2. The fluid circuit 30 includes a plurality of flexible plastic tube segments which form fluid conduits between various components of the fluid circuit. As shown in Figure 2, whole blood derived from a donor is conveyed through a first tubing segment 31 and a first peristaltic-type whole blood (WB) pump 32 to a hollow fiber-type filter 33 mounted on support rod 25. The operation of the WB pump is monitored by a positive.pressure (+P) monitor circuit 34 connected to tubing segment 31 downline of the WB pump by a tubing segment 35. Negative pressure, such as might occur upon the collapse of a vein, is monitored for by means of a negative pressure (-P) monitor circuit 36 connected to tubing segment 31 upline of the WB pump 32 by a tubing segment 37.

To prevent blood from clotting while in process in the apparatus anticoagulaht solution from a supply container 38 is introduced at the point of blood withdrawal through a tubing segment 39. A peristaltic-type pump 40 is provided along tubing segment 39 to provide a controlled rate of addition of the anticoagulant fluid to the whole blood.

Plasma separated from the whole blood within the hollow fiber filter 33 is conveyed by a tubing segment 41 to a plasma collection container 42. The pressure provided by WB pump 32 is sufficient to cause flow from the filter to the collection container. The plasma-deficient processed blood from filter 33 is conveyed through a tubing segment 43 to an ultrasonic bubble detector 44, which may be similar in structure and operation to that described in the copending application of Arnold C. Bilstad and Michael Wicnienski, entitled, "Liquid Absence Detector", Serial No. 127,552, filed March 6, 1980. Basically, bubble detector 44 includes a hollow housing having an internal filter screen assembly 45. Any bubbles in the processed blood fluid to collect at the upper portion of the housing. An ultrasonic sound transmitter 46 and an ultrasonic sound receiver 47 positioned at opposite sides of the upper portion of the housing detect bubble formation. The source 46 and detector 47 are connected to a dual bubble detector circuit 48 which provides first and second independent bubble detector (BD) outputs upon the occurrence of a bubble or liquid absence. Replacement fluid is added to the plasma-deficient blood at this location through a tubing segment 50 which is connected at one end to a replacement fluid container 51 and at its other end to the housing of bubble detector 44. A peristaltic-type replacement pump 52 is positioned along tubing segment 50 to establish a controlled flow rate for the replacement fluid. The combined plasma-deficient whole blood and replacement fluid are pumped from bubble detector 44 back to the donor through a tubing segment 53.

As shown in Figure 1, the processor unit 21 of plasmapheresis apparatus 20 is housed in a cabinet 54 which includes a sloped front upper portion on which a control panel 55 and the anticoagulant pump 40 are located. The cabinet also includes a sloped front lower portion on which the WB pump 32 and replacement pump 52 are mounted, together with the inlet to the positive pressure monitor 34 and the inlet to the negative pressure monitor 36. When flow system 30 is installed on the plasmapheresis apparatus, the anticoagulant container 38, replacement fluid supply container 51 and plasma collection container 42 are suspended from the overhead monitoring and control unit 22 as shown, and the hollow fiber filter 33 is mounted by means of an appropriate mounting bracket 56 to vertical support rod 25. Bubble detector 44 is similarly mounted to support rod 25 by means of a mounting bracket 57, and the ultrasonic source 46 and detector 47 thereof are electrically connected to processor unit 21 by an electrical cable 58.

Control panel 55 includes operator-actuated controls for operating the plasmapheresis apparatus. These include a selector switch 60 by which the operating speed of the anticoagulant pump 40 is set, a potentiometer control 61 and digital readout 62 by which the operating speed of the WB pump 32 is controlled, and a potentiometer 63 and digital readout 64, by which the operating speed of the replacement pump 52 is controlled. A plurality of pushbutton switches 65 are provided to establish the operating mode of the apparatus, and a plurality of status-indicating lights 66 provide indications of malfunctions in the system. The processor unit 21 in conjunction with flow circuit 30 constitutes a complete plasmapheresis system which may be operated without monitor and control unit 22. Thus operated, the system includes 5 no provision for directly indicating the total volume of plasma actually collected or the rate of plasma collection, and no capability for automatically operating the reinfusion pump to maintain a desired volume ratio with plasma collected in the plasma

10 collection container. Instead, during reinfusion the reinfusion rate is calculated from the volume of plasma collected over a known time period, and the result is manually set by means of control 63 and readout 64. The collection monitor and reinfusion

15 control unit of the invention can be easily added at any time by merely plugging cable 27 into a connector 67 (Figure 2) provided on the processor unit 21.

Basically, within the processor unit 21, the WB pump 32 is driven by a motor 70 having a

20 mechanically coupled tachometer 71. Power for operating motor 70 is provided by a motor control circuit 72 which responds to rate setting means in the form of potentiometer control 61 and a feedback signal from tachometer 71 to maintain a desired motor

25. operating speed. The actual pump flow rate is displayed by readout 62 as part of a display circuit 75, which receives the output signal from tach 71.

Similarly, the replacement pump 52 is driven by a motor 76 having an associated tachometer 77.

30 Power for motor 76 is provided by a motor control circuit 78 which responds to a feedback signal from tachometer 77 and the rate selected by the panel-mounted potentiometer 63 to maintain a desired constant motor speed. The actual pump flow rate is displayed by readout 64 as part of the display circuit 75.

The anticoagulant pump 40 is driven by a stepper motor 78 having an associated tachometer 79. Drive signals for motor 78 are developed by a motor control circuit 80 which responds to rate selection ^" switch 60 to maintain a desired constant anticoagulant flow rate.

The operation of the various pump motors is controlled by a processor control circuit 81 which includes mode select pushbuttons 65 on front panel 55. System malfunctions, such as negative pressure at pressure monitor 36, or excessive positive pressure at pressure monitor 34, or the occurrence of a bubble or other fluid absence as signaled at the first output (BD1) of the dual bubble detector circuit 48, result in-the application of an appropriate signal to the processor control circuit 81. This circuit responds by producing a control signal on a first motor control line 82 to the pump motor control circuits 72, 78 and 80 to interrupt operation of the motors. In addition, an alarm 83 associated with the processor control circuit 81 may be sounded and an appropriate one of indicator lamps 66 may be lit to alert the operator.

OMPI The processor unit 21 further includes a failsafe circuit 84 which functions to remove power from the pump motors in the event that processor control circuit 81 fails to respond to a system malfunction. To this end, the outputs of motor tachs 71, 77 and 79 are applied to the failsafe circuit, together with the second output (BDI) of bubble detector circuit 48.. Upon the occurrence of a bubble or fluid absence, as signaled by bubble detector circuit 48^', failsafe circuit 84 determines from the simultaneously applied tach output signals whether the pump motors have in fact stopped and, if motion is detected after a period of time, provides an additional stop signal which removes motor operating power to motor control circuits 72, 78 and 80 on a second motor control line 85.

As shown in Figure 1, the collection monitor and replacement fluid ratio control unit 22 of plasmapheresis apparatus 20 includes a housing 90 which extends between the vertical mounting posts 25 and 26 at a height sufficient to allow the various collection and supply containers 38, 42 and 51 to be suspended underneath. The housing includes a downwardly inclined front panel 91 on which a first digital readout 92 is mounted for indicating the volume of plasma collected, and a second digital readout 93 is mounted for indicating the rate of plasma collection. A selector switch 94 allows the user to condition monitor and control unit 22 to provide a desired replacement ratio in the exchange

OMPI mode, or to select the autologous mode, in which with an appropriate flow system a fixed volume of collected plasma is maintained in collection container 42 as plasma is withdrawn, processed and returned to the donor.

As shown in Figure 1, collection monitor and control unit 22 includes, in accordance with one aspect of the invention, a strain-gauge transducer 100 from which the plasma collection container 42 is suspended. The transducer is incorporated in a circuit 101 which develops an analog output signal having a voltage level dependent on the weight of collection container 42 and the collected plasma therein. The transducer output signal is applied to a voltage-to-frequency converter 102 which develops in a manner well known to the art a variable frequency weight-indicative output signal. This signal is applied to volume derivation circuits 103, wherein frequency variations over successive time intervals are analyzed and stored in accordance with the invention to develop a cumulative volume collected signal. This signal is applied to volume display 62, which provides a digital display of plasma volume collected. Volume derivation circuits 103 also produce collection pulses indicative of each incremental amount or unit of plasma collected. These pulses are applied to rate derivation circuits 104 wherein they are accumulated over a time period to obtain an ouput signal indicative of the plasma collection rate. This signal is applied to rate display 64, which provides a digital display of the plasma collection rate. The volume collection pulses are also applied to replacement ratio control circuits 106. These circuits compare the number of collection pulses, representing the volume of plasma collected, with replacement motor tach pulses conveyed from processor unit 21 over a line 107, representing the volume of replacement fluid replaced, and develop an appropriate analog speed control signal for application to the replacement motor control circuits 78 over a line 108. An operator-selected ratio set by switch 94 is automatically maintained by the ratio circuits.

In the event that volume derivation circuits 103 or ratio control circuits 106 detect an over-limit condition in their processing circuits, respective over-limit circuits 110 and 111 provide an over-limit alarm signal on a line 112 for application to control circuit 81 of the processor unit.

Reset of volume display 62 and ratio control circuits 106 when processor 21 is in the prime mode is accomplished by a reset line 113. Reset is also accomplished during initial power-up of the apparatus by a conventional power-up reset circuit 114 connected to reset line 113. Timing pulses required for the various circuits of unit 22 are provided by a clock circuit 115 within the unit. Basically, this clock circuit provides MEASURE and MEASURE clock pulses which establish measurement intervals, during which certain measurement functions are accomplished, and compute intervals, during which certain signal analysis and data transfer functions are accomplished; and a series of clock pulses T, -T₄, which sequence the data processing functions during the compute period.

Referring to Figures 3 and 4, the electrical strain-gauge transducer 100 is mounted to the bottom of housing 90 by machine screws 121 or other appropriate mounting means. This transducer, which may be conventional in construction and operation, includes at its unsupported end a protruding sense pin 122 from which the plasma collection bag 42 is suspended by means of a clip 123 or other appropriate means.

As shown in Figure 5, transducer 100 provides a conventional resistance bridge circuit having an output resistance dependent on the force exerted on sense pin 122. A regulated voltage source 124 is connected to the input terminals of the bridge network, and the output terminals of the network are connected to a differential amplifier 125 in accordance with conventional practice. The output of amplifier 125, which constitutes an analog voltage amplitude dependent on the strain exerted on the transducer, is applied to voltage-to-frequency converter 102. This circuit generates an output

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OMPI signal which has a frequency proportional to the applied analog voltage, and hence to the downward force (or weight) exerted on sense pin 122 of the transducer. In practice, transducer circuit 101 may be designed in accordance with conventional and well-known techniques to provide in conjunction with converter 102 arr output signal having a 10 hertz variation in output frequency for each milliliter of plasma collected in plasma collection container 42, and various conventional compensating and offset circuits (not shown in Figure 5) may be incorporated in the circuitry associated with transducer 101 to obtain a more linear and temperature independent output. Typically, for an offset voltage of one volt at the input of differential amplifier 125, a base frequency of 10,000 hertz may be realized at the output of converter 102.

Referring to Figure 6, the output signal from voltage-to-frequency converter 102 is applied to a conventional frequency divider 127, which divides the 10,000 hertz signal to develop a 1,000 hertz pulse signal having a deviation of 1 hertz per milliliter of plasma collected. In accordance with the invention, within volume derivation circuits 103 the 1,000 hertz variable-frequency signal is periodically applied during measurement intervals of fixed time duration to an input counter 130, which counts the pulses during each measurement interval to develop an output

OM I signal at the end of each measurement interval indicative of the pulse frequency during the interval. In illustrated plasmapheresis apparatus, the measurement intervals are obtained by application of a MEASURE clock pulse developed by clock 115 to inhibit input of frequency divider 127, which has the effect of enabling the divider, and hence counter 130, during measure intervals. By selecting a measurement interval of one second, the counter output at the end of the measurement interval is made^* to equal the frequency of the transducer signal in hertz. • However, other measurement intervals may be selected if appropriate.

Following each measurement interval, the counter output is added in an A+B binary adder 131 with a previous inverted output of the counter, as stored in a latch register 132. Consequently, the output of the binary adder is a difference signal representative of the difference between the two counter outputs. If the difference between the counter outputs represents a collection increment which is physically possible by processor unit 21 in the selected measurement interval (in the present embodiment either 0, 1, 2 or 3 collection units within a one second interval), as determined by logic circuitry within control circuits 133, then the output of the binary adder 131 is converted upon the occurrence of a T₂ (latch) clock signal to a serial signal consisting of either 0, 1, 2 or 3 collection pulses within a parallel to serial converter 134.

fUP.E_^ ^' OMPI These collection pulses are applied to a display counter 135 through an AND gate 136, and to an output line 137 for application to utilization means such as rate deviation circuits 104 and rate control circuits 106 of the apparatus. Display counter 135 periodically displays the accumulated count upon receipt of a T₂ (latch) clock pulse.

Display counter 135 accumulates the applied pulses for the duration of each plasmapheresis procedure. By adapting the voltage-to-frequency' converter 102 to provide a 1 hertz deviation in frequency for the equivalent weight of each milliliter of plasma collected, the accumulated count in counter 135 may be read out directly on the digital volume collected display 62 as milliliters of plasma collected. Display counter 135 is reset only upon completion of the plasmapheresis procedure by a total volume reset pulse on reset line 113. Counter 135 is periodically reset following each measurement interval by a T . (reset) clock pulse.

If the output of binary adder 131 is greater than 3 units, representing the physical impossibility in the illustrated plasmapheresis system of more than 3 milliliters of plasma being collected in one second, or of more than 180 milliliters being collected in one minute, then the difference is considered invalid by control circuits 133 as having been caused by a physical disturbance to the collection container and no increment is added to display counter 135. Also, when the output of binary adder 131 is negative, as indicated by the absence of an appropriate carry output on its carry line 138, corresponding to a loss of plasma impossible in the system, the differential is considered invalid and no increment is added.

To provide a meaningful reference from which to measure the deviation, register 132 is latched by ₃ (load) clock pulses applied through an AND gate 139 to assume the existing reading of counter 130 after the differential output of binary adder 131 has been analyzed and, if valid, incremented to counter 135. This is done in all instances, except if the differential output of binary adder 131 is negative and less than 3 milliliters. In this case register 132 is not latched and therefore retains the previous count of counter 130, and the subsequent deviation is taken from the stored count. This precludes slight flow irregularities such as might result during normal operation of the apparatus from affecting the count.

Additional protection is provided against physical disturbances to the collection bag by circuitry in control circuits 133 which causes the differential output of binary adder 131 to be taken as invalid, and register 132 to not be latched for four measurement intervals, following a differential output from binary adder 131 greater than 3. This prevents small transient disturbances to the collection container or flow system, such as might occur for a period of time following a large disturbance to the flow system or apparatus, or following a change of collection containers, from affecting the accuracy of the collected volume display and the collection pulses produced by the flow system.

The operation of the volume derivation system is tabulated for a system having a maximum collection rate of 3 milliliters per second as rules I-IV in Figure 7. If V is taken as plasma volume (based on weight) in a 1 second interval, and 6V as ^' the change in volume (based on weight) between successive one second intervals, then it is seen that only those positive volume changes which are either 1, 2, or 3 milliliters in the one second interval, and therefore fall under rule II, are recognized as valid collection increments to be applied to display counter 135. This is illustrated in Figure 8 by a hypothetical plot of plasma volume (based on weight) over time intervals t_Q - t,₃« At an initial time t_Q the A and B inputs to binary adder 131 are both identical. Consequently, according to rule III of Figure 7 the differential output A-B is 0, an increment of 0 is produced, and the collected volume count in counter 135 is 0. At time t.. , the immediately preceding .count is applied to input A, and the next preceding count is applied by register

OMPI 132 to input B. The resulting A-B differential signal is +1, and in accordance with rule II a 1 milliliter increment is produced for application to display counter 135, resulting in a cumulative count in that counter of 1.

At time t~ the B input of binary adder 131 is a binary one contained in register 132, and the A input is a binary four from counter 130. The +3 differential results in three pulses being incremented to display counter 135, causing the counter to assume a counting state of 4. Examination of the curve of Figure 8 at this time will show that in fact four units of plasma have been collected. At time t₃ register 132 has assumed the four count of counter 130 at the end of the previous measurement interval. Input counter 130 now reads 8, making the differential output of adder 131 a +4. In accordance with rule I of Figure 7, this results in a 0 increment being supplied to display counter 135. Since the deviation exceeded 3, a four period delay is initiated before binary adder 131 can increment counter 135.

After the four period delay under rule 1, any transient disturbances will have dissipated, and the system resumes analyzing received data at time t_. From time ₇ to time t_fl, the indicated volume falls to four units, producing a differential of -4. Under rule IV, a zero is incremented to display counter 135 and another four second delay period t_Q - t.... is initiated. At time t₁₂, a -28-

differential of -2 is realized. Under rule III this results in no incremental output and no change in the cumulative plasma collection count, which remains a 4 units. However, register 132 is caused to retain its four count from time t_Q until time t₁₃« At time t.._g however, a +1 increase is recognized by binary adder 131. This causes an increment of one pulse to be applied to display counter 135, and the resulting count in that register to be 5 units of volume. This volume is displayed by the total volume display 62.' By comparing the collected volume of plasma at time t_Q with that at time t,₃, it. is seen that 5 units of plasma have in fact been collected. Those large positive or negative excursions (in excess of three milliliters in the illustrated apparatus) are considered by the system as not resulting from plasma collection, but from the application of external forces to the transducer, as when changing the plasma collection container, and are accordingly ignored in computing total volume collected. Similarly, since a negative collection fate is physically impossible, small negative excursions of less than 3 milliliters are viewed by the system as chance events which even themselves out with time, and are therefore not accumulated.

Referring to Figure 9, the clock pulses required for operating the various circuits of the collection monitor and reinfuse control unit 22 are supplied by an oscillator 140 six decade counters 141-146, and one flip-flop 147 within clock circuits 115. Counters 141-146 are connected to oscillator 140.in a conventional manner to obtain 200 kHz, 50 kHz, 5 kHz, 1 kHz and 1Hz clock pulses. The 1 Hz clock pulses and the 200 kHz clock pulses are applied to the reset and clock inputs, respectively, of a decade divider 148. This divider functions as a Johnson counter to produce a series of output pulses - following each reset pulse from flip-flop 147. Since the clock pulses applied to the divider are at a relatively high frequency, the sequence of pulses T₁ - 1. is generated by the divider within a short time interval.

After the divider has completed the pulse sequence T.. -T,, an output T_g is generated. This output is applied to the inhibit input of the divider to prevent further counting, and to one input of an OR gate 149. The other input of OR gate 149 receives a T_Q output from the divider, causing the gate to produce a MEASURE control signal on a line 150 whenever the divider is reset and not counting. An inverter 151 connected to the output of OR gate 149 produces a NOT-MEASURE control signal on a line 152.

As illustrated in Figure 10, the MEASURE control signal developed by decade divider 148 provides the 1 second measurement period during which counter 130 counts pulses from divider 127. Following each such measure interval, upon application of a reset pulse to decade divider 148, a 40 microsecond computing period occurs while divider

-gTTE OMPI 148 counts through its cycle. Clock pulses T. - T . , which are associated with prelatch, latch, load and reset functions, respectively, of circuits 103, 104 and 106, occur during this compute period. Since clock pulses T. -T . are obtained at alternate outputs of divider 148, a time space exists between the clock pulses which precludes any overlap in the functions they control.

Referring to the schematic diagram of the volume derivation circuits shown in Figure 11, the weight-dependent variable frequency signal from the divide by ten counter 127 is applied to a trio of counters 160-162, which collectively perform the function of counter 130 of Figure 6. The most significant, digit of each counter output is taken as the carry output and is connected to the clock input of the next succeeding counter. Thus, the presence of an output signal on the most significant digit of counter 160 results in a carry signal to counter 161, and the presence of a signal on the most significant digit of counter 161 results in a carry signal to counter 162. This allows a total count of 12 digits to be accommodated by the counters.

In the event that a predetermined maximum count allocated to the three counters is exceeded, as evidenced by outputs at the two most significant digits of counter 162, an AND gate 163 produces an over limit indicative output which inhibits counter 127 through an OR gate 164. This over-limit inhibit continues until counters 160—162 are reset following the measurement interval. As previously described, the divide-by-10 counter 127 is inhibited during compute intervals by a MEASURE clock pulse applied through OR gate 164. This prevents the application of transducer pulses to counters 160-162 after a count has been completed, thereby providing an unchanging output from the counters during the comparison period. Counters 160-162 are periodically reset by a T. clock pulse, which as seen in Figure 10 occurs at the end of the clock period.

The outputs of counters 160-162, which are in parallel binary format, are applied to the A inputs of respective binary adders 165-167, which collectively perform the function of binary adder 131 in Figure 6, and to the inputs of respective latch-type registers 168-170, which are each connected to provide an inverted output and which collectively perform the function of latch register 132 in Figure 6. The outputs of registers 168-170, in binary inverted-parallel format, are applied to the B inputs of respective ones' of binary adders 165-167.

To provide the carry function necessary for cooperative operation of the binary adders, the carry output of adder 165 is connected to the carry input of adder 166, and the carry output of adder 166 is connected to the carry input of adder 167. The carry output of adder 167 is connected to the carry input of binary adder 165 by an end-around carry line, and to other circuits within the plasmapheresis apparatus

OMPI by a carry signal line 138. Adders 165-167, thus connected, function in a manner well known to the art to produce an output signal equal to the difference between the output of counters equal to the difference between the ouput of counters 160-162, applied direct to the A inputs of the adders, and the stored output of the counters, applied through inverted registers 168-170 to the B inputs of the adders. The parallel binary format outputs of binary" adders 165-167 collectively provide a 12-digit signal representing the difference between the binary signals applied to the A and B inputs of the adder devices. The ten most significant digits of this signal are applied to signal analysis means in the form of a 10 input OR gate 172 and a 10 input NAND gate 173. The output of OR gate 172 is applied through an AND gate 174 to one input of an OR gate 175. The output of NAND gate 173 is applied through an AND gate 176 to the remaining input of OR gate 175. The carry output of binary adder 167 is connected to the remaining input of AND gate 174 and through an inverter 177 to the remaining input of AND gate 176. The arrangement of logic gates 172-177 is such that an output is produced by OR gate 175 only if the output of binary adders 165-167, as determined by the presence or absence of outputs on the ten most significant digits of the twelve digit output signal, exceeds an absolute value of three. In the presence -33-

of a carry output from binary adder 167 the difference output is taken as positive, and AND gate 174 is enabled and AND gate 176 is inhibited. In the absence of a carry signal from adder 167 the difference output is taken as negative and AND gate 174 is inhibited and AND gate 176 is enabled. Thus, during a negative output NAND gate 173 is determinative and provides an output only in the presence of a logic low condition on any one of the monitored outputs from the ten most significant digits of adders 165-167. Conversely, during a positive output, gate 172 is determinative and provides an output through OR gate only in the presence of a logic high condition on any one of the monitored outputs of binary adders 165-167.

The output of OR gate 175 is applied to one input of an OR gate 179 and to the parallel enable input of a shift register 180. The other input of OR gate 179 is connected to the carry output of binary adder 167, so that upon the occurrence of a difference in excess Of absolute 3, or a positive carry output on line 168, OR gate 179 is enabled. The output of this gate is applied to one input of AND gate 139. Another input of AND gate 139 is connected to receive the T₃ (load) clock pulses, and the remaining input is connected to receive an Ml mode control signal generated in replacement fluid flow ratio control circuits 106 to signal selection by switch 94 of operation of the monitor and control unit 22 in an autologous mode. As a result, registers 168-170 are clocked at time T_ during the compute period to assume the counting state of counters 160-162.

Shift register 180 functions to provide a delay period of four measurement intervals following the occurrence of a differential count in excess of absolute 3. To this end, in the event of a logic low output from OR gate 175, shift register 180 is enabled in a serial mode and provides an output following the application of four T. (pre-latch) clock pulses to its clock input terminal. This output signal is applied to an AND gate 182 which controls the application of ₂ (latch) clock pulses to parallel to serial conversion means in the form of programmable counter 183. These pulses condition counter 183 to a parallel mode.

The two least significant digits of the twelve digit difference signal developed by binary adders 165-167 are applied as a parallel-loaded input to counter 183. In its parallel mode the counter counts either zero, one, two or three pulses, corresponding to the two digit parallel-loaded signal from binary adder 165, before producing an output signal. The output of counter 183 is applied through an inverter 184 to one input of an AND gate 185, which is also connected to the inhibit input of counter 183 the other input of AND gate 185 is connected to the 1 kHz clock pulse source. Gate 185 is enabled until counter 183 produces an output, so

-£TRE

OMPI_.. that either zero, one, two or three pulses are produced at a 1 kHz rate at the output of the gate according to the two binary digits applied to counter 183. The output of inverter 184 is also coupled to the clock input of the counter to terminate operation of the counter after the required counting state has been reached.

Counter 183 is prevented from counting when the differential output of adders 165-167 is greater than absolute 3, and for a four interval delay thereafter, or in the event of a negative differential, by AND gate 182, which controls the application of T₂ latch pulses to the. parallel enable input of the counter. Application of these latch pulses to counter 183 enables the counter to assume the count of the parallel-loaded digits from adder 165.

Counter 183 counts down from the parallel-loaded count, and zero, one, two or three pulses are developed at the output of AND gate 185 and applied through AND gate 136 to a display counter 187. The remaining input of AND gate 136 is connected to the Ml control line so that gate 136 is inhibited, and the zero, one, two or three pulse increment produced by counter 183 is not applied to the clock input of display counter 187 if the apparatus is in the autologous mode.

Display counter 187 operates in a conventional manner to accumulate the pulses applied by AND gate 136. The accumulated count is transferred to a display output each time a ₂ (latch) control signal is applied to the latch input of the counter. The count assumed by display counter 187 is applied to three conventional seven-segment display panels 188-190 which are enabled by counter-generated strobe signals in a conventional manner through inverter amplifiers 191-193 to display the accumulated count with three digit accuracy. The count accumulated in display counter 187 is reset to zero only upon the application of a volume reset signal to the reset terminal of the counter. Normally this occurs on reset line 113 only during initial power-up of the apparatus, or when changing operating modes. In the event that counters 160-162 exceed a predetermined limit, an alarm is sounded after a one second delay. To this end, the output of AND gate 163 is applied directly and through an inverter 191 to the J and K inputs of a JK type flip-flop 192. T. (reset) clock pulses are applied to the reset terminal of this flip-flop and the outputs of the flip-flop are coupled to the inputs of a second JK flip-flop 193. The set input of flip-flop 193 is connected to the power-up reset line 194 of the apparatus, so that upon initial power-up flip-flop 193 is not actuated. A limit alarm is provided by the ouput of flip-flop 193 through an inverter 195. The variable-frequency output pulses from voltage-to-frequency converter 102 are applied to the clock input of flip-flop 192 to render the operation of that flip-flop subject to the occurrence of additional output pulses from the transducer circuit. In operation, the variable frequency signal from voltage-to-frequency converter 102 is applied to counters 160-162, causing these counters to count up until the application of pulses is interrupted by OR gate 164 and counter 127 being inhibited by the

MEASURE clock signal at the end of the measurement interval. At this time counters 160-162 provide a 12 digit output signal indicative of the frequency of the applied weight-indicative signal, and adders 165-167 provide an output signal corresonding to the difference between this signal and the previous counter output signal as applied inverted by latch registers 168-170. All but the two least significant digits of the output signal are analyzed by logic gates 172-177 to determine whether the difference is greater than absolute-three. If the difference output is less than three, and providing the output is positive as indicated by the presence of a logic high condition at the carry output of binary adder 167, programmable counter 183 is parallel-enabled by a T₂ (latch) clock pulse through AND gate 182 and counts down through the number of steps dictated by the applied two least significant digits to produce at the output of AND gate 185 either zero, one, two or three pulses at a 1 kHz rate. These pulses are applied to and accumulated in display counter 187, which upon receipt of the ₂ (latch) clock pulse indicates on display panels 188-190 the accumulated volume of plasma collected. In the event that the carry output of binary adder 167 is logic low, corresponding to a negative output from the binary adders, AND gate 182 is inhibited and counter 183 remains inhibited. This results in no output at AND gate 185 and no incremental pulses being applied to display counter 187. In the event that the difference developed by binary adders 165-167 exceeds an absolute three, shift register 180 is enabled in its parallel mode and inhibits AND gate 182 for four subsequent occurrences of T.. (pre-latch) clock pulses after the difference becomes less than absolute 3. Also, in the event of a negative difference less than three, OR gate 179 inhibits AND gate 139 to prevent registers 168-170 from responding to the next T_ (load) clock pulse to assume the counting state of counters 160-162. As 'previously explained, this prevents registers 168-170 from assuming a new counting state following a negative incremental change of less than absolute three. The sequence of the clock pulses T.-T. is such that the application of pulses to counters 160-162 is first terminated by the measure control signal applied to OR gate 164, after which the delay shift register 180 is stepped by the T, (pre-latch) clock pulse. Next, AND gate 182 and display counter 187 are enabled by a T₂ (latch) clock pulse to transfer data. Then, registers 168-170 are latched to a new count by a T₃ (load) clock pulse, after which counters 160-162 are reset by a T (reset) clock pulse.

Referring to Figure 12, the plasmapheresis apparatus includes, in accordance with the invention, a rate derivation circuit 104 which derives from the serial collection pulses of volume derivation circuit 103 a digital display of plasma collection rate. Within the rate derivation circuit the pulse-per-milliliter collection pulses are applied to a shift register 200. This register, which may be conventional in structure and operation, has data positions for storing the serial data received from volume derivation circuits 103 over sixty preceding one second measurement intervals. Since in the illustrated plasmapheresis apparatus each measurement interval results in the production of either zero, one, two or three one -milliliter serial collection pulses, or data bits, three data positions are reserved in register 200 for each of the sixty measurement intervals to be taken into account. Thus, 180 data positions are provide in register 200. When the three data bits for each measurement interval have been entered into register 200 for the preceding 60 intervals, the register contains a count total equal to the total number of milliliters of plasma collected over the preceding 60 intervals. If each interval is one second in

OMPI _ duration, then the counting state of the register represents the number of milliliters collected in the preceding minute, which may be read as the collection rate in milliliters per minute. The operation of shift register 200 is conventional in that, the addition of each new bit of data at its input results in the overflow of one bit of data at its output. Thus, if three data bits are loaded at its input, three data bits are produced at its output. Since the data bits advance from input to output, the most recent data is located at the input of the register, and the oldest data is located at the output of the register. Consequently, when three data bits are entered representing the most recent data in a 60 second or one minute, analysis period, the three data bits produced at the output represent data occurring before the analysis period. Thus, only collections in the previous minute are recorded in shift register 200. To provide a display of the rate of plasma collection, the data bits contained in shift register 200 are periodically applied through appropriate switching means such as an AND gate 201 to a display counter 202. To this end, clock pulses are applied to shift register 200 to cause data within the register to appear serially at the output of the register. With AND gate 201 enabled, this data is applied to display counter 202, wherein the total number of collection pulses in the data is accumulated as a count representative of the number

OMPI of milliliters of plasma having been collected in the preceding analysis period. The total count developed by counter 202 is displayed by collection rate readout 93 in milliliters of plasma collected per minute.

Shift register 200 has A and B inputs selected by application of a signal to its A/B select input. To update the rate display to reflect changes in flow rate, new data consisting of three bits for a new measurement interval is applied to the A input of shift register 200. Control circuits 203 enable the A input and apply appropriately timed clock pulses. The oldest three data bits in the register appear serially at the register output as the new bits are entered. Control circuits 203 inhibit AND gate 201 at this time to prevent the three oldest bits from being applied to display counter 202. Since the B input of the shift register is inoperative (not selected), the bits are not recirculated back into the register and cease to exist.

After the three new data bits have been applied to the A input, control circuits 203 cause the B input to be selected and AND gate 201 to be enabled_* Clock pulses now applie to shift register 200 recirculate all 180 data bits in the register from the output back to the B input. At the same time, the same 180 data bits are applied through the enabled AND gate 201 to display counter 202, which has been reset by a . (reset) clock pulse prior to the loading operation. After the 180 data bits in the register have completely recirculated, the application of clock pulses to the register is terminated, AND gate 201 is inhibited, and a ₂ (latch) clock pulse is applied to display counter 202 to cause that counter to display the count of the pulses just applied. Digital display 93 displays this count to the operator as milliliters of plasma collected per minute. At the completion of the next measurement . cycle a new set of collection data is produced by volume derivation circuits 103. Prior to receiving this data, control circuits 203 condition the A input of shift register 200 operative and inhibit AND gate 201. Then, after the new data has been received, display counter 202 is latched, AND gate 201 is enabled, and an additional 180 clock pulses are applied to shift register 200 to transfer the new data to counter 202 to begin the cycle anew. Referring to Figure 13, if each measurement interval is considered as having three data positions designated A, B and C, then after an initial 60 intervals shift register 200 may appear as shown by data group 210. If 180 clock pulses are now applied to the shift register an output data group 211 comprising data bits A, through C,_g0 will be applied to display counter 202. Subsequently, if new data ₆₁, B_gl and C_g, is introduced into the register, the A,, B, and C-. data is lost and the register contains data as shown by data block 212. This data is read to display counter as A₂-C_8l as shown by data block 213. If a third set of data comprising A_g2 - C_β2 is entered, then the next oldest data A₂~C₂ is dropped, and the shift register assumes the data state shown by data block 214.

Referring to Figure 14, within rate derivation circuits 104 control circuits 203 may include a first programmable counter 220, a second programmable counter 221, a D-type flip-flop 222 and- a JK-type flip-flop 223. To derive the necessary clock pulses for shifting data within shift register 200, 1 kHz pulses from clock 115 are applied directly to the D input of flip-flop 222, and through a NAND gate 224 to the clock input of counter 220. This counter includes an asynchonous parallel enable (APE) input to which a T₂ (latch) clock pulse is applied through an inverter 225 during each compute interval. Upon the occurrence of each ₂ clock pulse, the counter is enabled in its parallel mode and a BCD count of 183_. is loaded into the counter through appropriate hard-wired parallel-entry connections.

Immediately following the termination of the T- clock pulse, counter 220 begins to count down from the pre-loaded 183 count to zero. As the count progresses the output of counter 220 is logic high, and a logic low signal is applied to the reset input of flip-flop 222 through an inverter 226. This allows flip-flop 222 to toggle at a 1 kHz rate as a result of the 1 kHz clock signal applied to its D input. A 2 kHz clock signal applied to the clock input of the flip-flop introduces a half-cycle time shift to the resulting flip-flop output signal. The time-shifted output pulses from flip-flop 222 are applied to the clock inputs of a programmable-length shift register 227, and to a static shift register 228. The input terminal of register 228 is connected to the output terminal of register 227 so that the registers operate together to perform the function of the single shift register 200 of Figure 12. In accordance with conventional practice, register 227 is hard-wired to provide 52 (of a possible 64) data positions, so that when this register is combined with the 128 positions available in 228, 180 data positions are available.

Shift register 227 has two inputs; an A input and a B input. Selection between these inputs is accomplished by connecting the A/B select input of the register to the output of programmable counter 221. Counter 221 has a binary hard-wired parallel-entry input, so that upon application of an enabling signal to its parallel-enable (PE) input, the counter assumes an initial count of 3. This is accomplished during each compute cycle by application of a T₂ (latch) clock pulse to the parallel-enable input. Following the ₂ clock pulse, the counter is counted down to zero by 1 kHZ clock pulses applied to its clock input.

OMPI The output of counter 221, whch assumes a logic high state upon the counter reaching zero, is connected to the inhibit input of the counter, to the A/B select input of shift register 227, and to one input of a four input AND gate 230. Thus connected, counter 221, before reaching zero, is enabled, and the B input of shift register 227 is selected. This input is connected to the collection pulse output line 137 of volume derivation circuits 103, so that upon the B input being selected shift registers 227^' and 228 receive whatever collection pulses are produced by parallel to serial converter 134 (Figure 6). Since the output of counter 221 is logic low when the counter is counting, AND gate 230 is disabled during the initial three data bits.

Following the application of three lkHZ clock pulses to the input of counter 221, the counter reaches zero, inhibiting further counts, enabling AND gate 230, and selecting the A input of register 227. This arrangement allows, in accordance with the invention, the three new data bits from volume derivation circuits 103 to be loaded into shift registers 227 and 228, and the oldest three data bits to be discarded. Counter 220, which provides 183 time-shifted clock pulses through flip-flop 222 to the shift registers, causes data bits to appear at the output of registers 227 and 228 at the same time programmable counters 220 and 221 are counting the initial three 1 kHz clock pulses. Since the output of counter 221 selects the B input of shift register

OMPI 227 at this time, the oldest three data bits produced at the output of register 228 cannot recirculate through the A input. However, new data bits (or collection pulses) from volume derivation circuits 103 are received on line 137 in the first three data positions of shift register 227.

After the first three bits have been counted, counter 221 reverts to a logic high output. This selects the A input of register 200 and enables AND gate 230. The next 180 clock pulses from counter^' 220 cause the 180 data bits then in shift registers 227 and 228 to be simultaneously recirculated through the A input of the shift register, and applied through AND gates 230 and 231 to the clock input of display counter 202. After 183 clock pulses have been applied to registers 227 and 228 by counter 220, the output of the counter reverts to a logic low state. This inhibits NAND gate 225 to prevent the application of additional clock pulses to the counter, and inhibits flip-flop 222 through inverter

226 to prevent the application of further time-shifted 1 kHz clock pulses to shift registers

227 and 228. Also, the logic low output of counter 220 is applied to an input of AND gate 230 so as to inhibit that gate after the counter has completed its 183 count cycle.

Shift registers 227 and 228 provide for successive logic high output states no discernible transition in output signal level. To separate such consecutive logic high states into separate pulses countable by display counter 232, the remaining input of AND gate 230 is connected to the output of a JK type flip-flop 223. This flip-flop is toggled in response to an applied 5 kHz clock signal to momentarily inhibit AND gate 230 between each data period so as to provide separation between consecutive data bits.

The remaining input of AND gate 231 is connected to the MT control line so that when the apparatus is in its autologous mode the AND gate is inhibited and data bits are prevented from reaching display counter 202. This inhibits the rate display during autologous operation.

Display counter 202 operates in a conventional manner to accumulate the pulses applied to the counter in a predetermined period of time. This period is established by a T₂ (latch) clock pulses periodically applied to the latch input of the counter, which cause the counter to display, in a manner well known to the art the then accumulated count of applied pulses. At the end of each compute cycle the display counter is reset by a T₄ (reset) clock pulse applied to its reset terminal. However, the counter continues to display the count at the time of the most recently applied latch pulse until application of a subsequent latch pulse, as is conventional for display counters. The counter provides seven outputs which are connected to each of three digital display components 233-235, which comprise the digital rate readout 93. These components are controlled by strobe signals from the counter through inverters 236-238 in accordance with conventional practice to indicate the count produced by the counter.

If, as in the illustrated plasmapheresis apparatus, each pulse applied to display counter 202 represents 1 milliliter of plasma collected, and the total count in shift registers 227 and 228 represents a sampling period of one minute (60 1 second measurement intervals), then the count displayed by^" readout 93 may be read directly in milliliters per minute. By updating the count in display counter 202 with the occurrence of each one second measurement interval, changes in flow rate may be quickly observed.

Referring to Figure 13, if each measurement interval is considered as having three data positions designated A, B and C, then after an initial 60 intervals shift register 200 may appear as shown by data group 210. If 180 clock pulses are now applied to the shift register-an output data group 211 comprising data bits A, through C._g0 will be applied to display counter 202. Subsequently, if new data A_g,, B_βl and C_g. is introduced into the register,

A«.,., B.. and C- data is lost and the register contains data as shown by data block 212. This data is read to display counter as A₂-C_8l as shown by data block 213. If a third

^•_Λ-_r_L set of data comprising A_g2 - C_g2 is entered, then the next oldest data ^A2~"^C2 ^"^{s ro}PP^e<3-r ^nd the shift register assumes the data state shown by data block 214. In further accordance with the invention and with reference to Figure 15, the collection pulses developed by the volume derivation circuits 103 of the invention are utilized by rate control circuits 106 to automatically control the rate at which ^• collected plasma is replaced, and to provide an autologous mode wherein collected plasma can be treated and returned to the donor. Basically, this system includes a rate multiplier circuit 240 to which the 1 milliliter collection pulses developed on line 137 by volume derivation circuits 103 are applied. Rate multiplier circuit 240 provides, in accordance with conventional practice, a selected number of pulses for each applied collection pulse. The number of pulses provided is dependent on an applied binary control signal developed within a read-only-memory (ROM)* 241. The magnitude of the binary control signal, and hence the multiplication factor of the rate multiplier circuit 240, is dependent on an input signal applied to ROM 241 by the ratio/mode select switch 94. The output of rate multiplier circuit 240 is applied to the up count input of an up-down counter 242.

Within replacement ratio control circuits 106 the tach output pulses from replacement motor tachometer 77 are applied to a second rate multiplier

OMPI circuit 243. The multiplication factor applied by this rate multiplier circuit is also dependent on an applied binary control signal developed by ROM 241, which is in turn also dependent on the ratio selected by the ratio/mode select switch 94. Thus, for a particular selected ratio, a predetermined number of output pulses will be produced by rate multiplier circuit 243 for each tachometer pulse received from tachometer 77. The output of rate multiplier circuit 243 is applied to the down count input of up-down counter 242.

With rate multiplier circuits 240 and 243 thus connected, the up-down counter 242 counts a predetermined number of counts in an up direction for each increment of plasma volume (weight) collected, and a predetermined number of counts in a down direction for each pulse received from the replacement pump motor tachometer. The counting state of the up-down counter 242 is indicated by a binary output signal. This signal is applied to a digital-to-analog converter 244 which converts the applied binary signal to an analog control voltage. This control voltage is applied by means of a control line 108 to the rate determining circuit 63 of replacement pump motor 76.

In operation, as plasma is collected in plasma collection container 42 transducer conversion circuits 101 produce output pulses at a frequency dependent on the weight of the collected plasma. Within volume derivation circuits 103 these

PI weight-related transducer signals are converted to an output signal providing one pulse per milliliter of plasma collected. These plasma collection pulses are applied within replacement ratio control circuits 106 to rate multiplier circuit 240, which provides a predetermined number of pulses to up-down counter 242 for each applied collection pulse, depending on the multiplication factor set by ROM 241. This causes up-down counter 242 to count up to successively higher counting states. Digital to analog converter 244 responds by generating an analog control voltage which increases in level with the increasing count. This control voltage causes motor control circuit 78 to energize motor 76 so as to pump replacement fluid into the flow system.

As motor 76 turns tach 77 provides output pulses which are carried on tach line 107 to rate multiplier circuit 243. In multiplier circuit 243 a multiplication factor is introduced dependent on the applied control signal from ROM 241. The resulting rate-multiplied pulses are applied to the down count input of up-down 242. These pulses cause that counter to count down, thereby tending to reduce the analog control voltage developed by digital-to-analog converter 244. Thus, a closed loop system is formed which functions to maintain a continuous count of plasma collected less replacement fluid infused by tending to keep up-down counter 242 at a zero counting state.

OMPI By varying the multiplication factors of rate multiplier circuits 240 and 243 it is possible to maintain a predetermined volume ratio between plasma collected and replacement fluid added. Referring to Figure 16, the factor set by rate multiplier circuit 240 may be considered the numerator, and the factor applied by rate multiplier circuit 243 may be taken as the denominator of the ratio maintained by the system. The necessary multiplication factors are set by ROM 241 in response to volume ratio selected by switch 94. For example, if a 1:0 ratio is selected, both rate multiplier circuits are set for a multiplication factor of 4 and up-down counter 242 receives four pulses for each increment of plasma collected and four pulses for each increment of fluid replaced. If a ratio of 0.5 is set, then rate multiplier circuit 243 is set for a factor of 4, and rate multiplier circuit 240 is set for a factor of 2. If a ratio of 2.0 is to be maintained, then rate multiplier circuit 243 is set to a factor of 4, and"rate multiplier circuit 240 is set for a factor of 8. In this way, a range of ratios from 0.5 to 3.5 is obtained in the illustrated plasmapheresis apparatus by the replacement rate control circuit 106.

To prevent operation of the plasmapheresis apparatus in the event that the reinfuse pump is unable to maintain the desired ratio, such as might occur were it to stall, the control circuit includes an overlimit circuit 246 which monitors the output of

OMP up-down counter 242 and provides an alarm output in the event the counter exceeds a predetermined maximum count. The alarm signal is conveyed over lead 112 through cable 27 for application to processor control circuit 81 to terminate operation of the plasmapheresis apparatus.

Since the operation of up-down counter 242 continues over continuous sampling periods, the counter is not reset following each measurement interval. Instead, the counter 242 is reset only upon a total volume reset, as when changing operating modes or upon initial power-up of the apparatus. Reset line 113 provides the necessary reset signal from the plasmapheresis apparatus through conductor 27.

An additional function of ROM 241 is to set the operating mode of the plasmapheresis monitor and control unit 22. To this end, ROM 241 provides Ml and M2 mode control signals according to the position of switch 94. These control signals are applied to the various circuits of the monitor and control unit to control and condition the circuits in accordance with the selected mode. When a reinfusion ratio is selected by switch 94, the Ml and M2 mode control signals are logic low to condition the circuits to the exchange mode. When the switch is positioned to the AUTOLOGOUS position both control signals are logic high to condition the autologous mode. An additional SCALE switch position, which allows weight-indicative transducer circuit pulses to be applied to rate readout 93, is provided by Ml being logic low and M2 being logic high. In the autologous mode of plasmapheresis apparatus 20 an alternative flow system is provided wherein collected plasma is pumped from collection container 42 to a secondary processing system for treatment, and then returned to a secondary processing system for treatment, and then returned to^' bubble detector 44 for recombination with the processed blood and return to the donor. Referring to Figure 17, the autologous mode flow system includes a tubing segment 250 which-extends from an outlet port of collection container 42 through replacement 52 to a secondary plasma treatment system, and a tubing segment 252 which extends from the treatment system to the chamber of bubble detector 44. These tubing segments replace tubing segment 50 and replacement fluid container 51 in the exchange mode system shown in Figures 1 and 2.

Upon operation of pump 52 plasma is pumped from the collection container through treatment system 251, and back into the donor through bubble detector chamber 44. Various types of plasma treatment may be accomplished in the treatment system, including the removal of excess quantities of certain antigens. A constant quantity of plasma is

OMP automatically maintained in collection container 42 during autologous mode operation by varying the speed of the replacement pump so as to match its pumping rate to the rate of plasma collection in container 42.. Referring to Figure 18, when replacement ratio control circuits 106 are configures for autologous operation the variable frequency pulses developed by conversion circuit 101 are applied to the up-count input of up-down counter 242 through an AND gate 253. The remaining input of^•AND gate 253 is^" connected to carry line 138, so that when the carry line is positive, indicating a positive difference between present and stored collected plasma volume, the AND gate is enabled and counter 242 is caused to count up in response to the pulses. Rate multiplier circuit 243 is at this time conditioned by ROM 241 to a zero counting state; so that a continuous logic high output is applied by the multiplier circuit to the down count input of counter 242. This enables the counter to respond to the pulses applied to its up count input. No reinfusion pulses from volume derivation circuits 103 or tachometer pulses from replacement motor tachometer 77 are utilized in this operating mode. An OR gate 254 allows the up-down counter

242 to be reset by either 1 hertz clock pulses or by a reset signal on the volume reset line 113. As in the ratio mode, over limit circuits 246 provide an alarm output in the event that the count in up-down counter 242 exceeds a predetermined limit, indicating that the balance in the plasma collection container 42 is not being maintained within limits. Within volume derivation circuits 103 the Ml control signal developed by ROM 241 inhibits AND gates 136 and 139 (Figure 6). This prevents the application of the ₃ (transfer) clock pulses to register 132 otherwise applied during each compute period. As a result, the register assumes and maintains the count of counter 130 at the time the apparatus is conditioned to the autologous mode. Counter 130 continues to receive and count pulses developed by transducer conversion circuits 102 during each measurement interval, and binary adder 131 develops the difference between each successive count of counter 130 and the stored count of register 132. However, the collection pulses developed by parallel-to-serial converter 134 are not applied to display counter 135 by reason of AND gate 136 being inhibited by the Ml mode control signal. Similarly, rate indicative pulses from shift register 200 are not applied to display counter 202 by reason of AND gate 201 being inhibited by the Ml mode control signal. Thus,, in the autologous mode, readouts 62 and 64 are both rendered inoperative.

The application of transducer output pulses to the up-down counter is initiated upon the carry output of binary adder 131 becoming positive. This occurs when the count reached by input counter 130

OMPI exceeds the count stored by register 132. Upon the carry output becoming positive, AND gate 247 is enabled and all subsequent transducer pulses developed by frequency divider 126 are applied to up-down counter 242. This causes counter 242 to count up, resulting in the development of ah analog control voltage by converter 244 upon occurence of the next occurring T₃ (latch) clock signal. The analog control voltage causes replacement motor 76 to operate to withdraw fluid from collection container 42. When sufficient fluid has been withdrawn from the collection container such that the count reached by counter 130 does not exceed the count stored in register 132, a carry output from binary adder 131 no longer present for any portion of the measurement interval and no transducer circuit output pulses are applied to up-down counter 242. Consequently, no analog control voltage is produced by converter 244 and the replacement motor 76 does not operate. Referring to Figure 19, the rate multiplier

240 may comprise a programmable counter 255 having a parallel-enable (PE) input to which collection pulses developed by volume derivation circuits 103 on line 137 are applied. This counter is programmed to provide a predetermined multiplication factor by means of a binary signal developed by ROM 241. To enable the rate multiplier to provide rate multiplication of the collection pulses clocked at 1 kHZ, the multiplier is clocked at 50 kHz by clock signals supplied to its clock input through an OR gate 256. Upon the occurrence of a collection pulse the programmable counter is enabled in its parallel mode, causing the binary count applied by ROM 241 to be parallel-loaded. At the same time OR gate 256 is enabled to allow the 50 kHz clock pulses to clock programmable counter 260 from the parallel-loaded count to zero. While the counter is counting, the output of the counter allows 50 kHz clock pulses to be applied through OR gates 257 and 258 to the count of up input of up-down counter 242. Upon reaching " zero, counter 255 provides an output which is applied to the inhibit input of the counter to inhibit further counting activity, and to one input of an OR gate 257 to inhibit the application of 50 kHz clock pulses to counter 242.

In the autologous mode the remaining input of AND gate 254 is alternatively supplied with f 1£ wt./lO transducer output pulses representing increments of weight on the transducer through an AND gate 260 and an inverter 261. The transducer pulses are applied to one input of the AND gate, and the other input of the AND gate is connected to the carry line 138 associated with binary adder 131 (Figure 6). The remaining input of AND gate 260 is connected to the Ml control line output of ROM 241. As a result, AND gate 260 is inhibited except when selector switch 94 is set to operate in an autologous mode. -In this mode the Ml control line assumes a logic high and AND gate 260 is enabled by carry line 138 when the count of transducer pulses by counter 130 in any measurement interval exceeds the reference count stored in register 132 at the beginning of the autologous procedure. When AND gate 260 is enabled transducer output pulses are applied through AND gate 260, inverter 261 and and gate 258 to counter 242.

In this mode a binary zero is applied to programmable counter 255 by ROM 241 to force a logic high at the other input of AND gate 254.

Pulses from the replacement motor tach are applied to a divide-by-sixty counter 262 which provides one infusion pulse for each sixty tach pulses. In the illustrated plasmapheresis apparatus this corresponds to one pulse per milliliter of fluid pumped by the reinfuse pump. The output from counter 262 is applied to a D-type flip-flop 263 which functions in a conventional manner in response to a 1 kHz clock pulse applied to its clock input to provide the synchronous pulse for each output of counter 262. The synchronized pulse is applied to the parallel entry (PE) input of the second rate multiplier 243, which, takes the form of a programmable counter 264.

This counter is conditioned^*to either a zero, four or ten counting state by ROM 241 upon the application.of each replacement pulse. OR gate 265 prevents 50 kHz clock pulses from being applied to counter 264 during the infusion pulse. Upon completion of the pulse counter 264 is counted down to zero by 50 kHz pulses applied to its clock input until a zero count is reached, at which time the output assumes a logic zero which inhibits further activity by the counter. While counter 264 is counting the 50 kHz clock pulses are applied through an OR gate 266 to the down count input of up-down counter 242. Upon counter 243 reaching zero OR gate 261 is inhibited to prevent the further application of pulses to counter 242.

The up-down counter 242 may comprise two separate up-down counters 267 and 268 connected together in a conventional manner to operate as the single counter of Figures 13 and 16. Specifically, the carry output of up-down counter 267 is connected to the count up input of counter 268, the borrow output of counter 267 is connected to the count down input of counter 268, and the clear inputs of the counters are connected together. Total volume reset control signals on reset line 113 are applied to the clear inputs of counters 267 and 268 through an OR gate 269. During each operation in the prime mode, T. (reset) clock pulses are also applied to the clear inputs of the counters through an AND gate 270 and the remaining input of OR gate 269. AND gate 270 is enabled by ROM 241 when switch 94 is positioned in either the AUTOLOGOUS mode or in the SCALE mode. This is accomplished by applying the M2 control signal developed by ROM 241 through an inverter 271 to the remaining input of AND gate 270.

The outputs of up-down counters 267 and 268 are applied to digital-to-analog converter 244. This converter is of the latch type, and is latched during each compute interval by a T, (load) clock pulse applied through an inverter 272 to the latch input of the converter. Consequently, in operation counters 242 reach their final count by reason of the sequence commanded by clock pulses T.-T₂, but the analog output of converter 244 does not change until a T- clock pulse commands a latch operation.

The binary outputs of counters 267 and 268 are monitored for an overlimit condition by NOR gate 273 and AND gate 274, which together comprise the previously identified overlimit circuits 246 (Figures 13 and 14)_.. The output of NOR gate 273, which has as its inputs the four least significant digits of the counter output signal, is applied through an AND gate 275 to the alarm circuits of the apparatus through line 112. The output of AND gate 274, which has as its inputs the four most significant digits of the counter output signal, is applied to the remaining input of AND gate 275 to signal an alarm condition. in addition, the output of AND gate 274 is applied through an inverter 276 to an analog switch device 277, which interrupts application of the analog control voltage developed by digital-to-analog converter 244 from application to the processor along control line 108.

In operation, during the exchange mode, collecton pulses are rate-multiplied by programmable counter 240 according to a factor set by ROM 241 and applied through OR gate 257 and AND gate 258 to the count up input of up-down counters 267 and 268. At

OMPI the same time, replacement motor tach output pulses from the processor are applied through counter 262 and flip-flop 263 to programmable counter 264. This counter applies a rate multiplication according to a factor set by ROM 241 to develop pulses for application to the count down input of counters 267 and 268 through OR gate 266. The ratio between counters 255 and 264 is set by ROM 241 in accordance with the setting of ratio/mode switch 94. Counters 267 and 268 provide an output signal dependent on the- - cumulative difference between the rationalized collection pulses and rationalized tach pulses. This binary signal is periodically recognized by digital-to-analog converter 244 upon occurrence of a ₃ (latch) clock pulse to produce an analog control voltage which is applied to the replacement motor through control line 108.

In the event of an initial over-limit alarm condition, indicated by the presence of an all logic low signals at the four least significant digits monitored by OR gate 273, OR gate 273 sounds an alarm in the processor through AND gate 275 and line 112. In the event a further limit is exceeded, accompanied by the four most significant digits becoming logic high, then AND gate 274 functions to interrupt the analog control signal by opening analog switch 277.

Counters 267 and 268 are reset only upon initial power-up, or during operation in the prime mode, or by AND gate 270 and OR gate 269 when operating in the autologous mode. The M2 control signal of ROM 271 inhibits AND gate 270 to prevent T . (reset) clock pulses from effecting a reset during the exchange mode.

In the autologous mode ROM 241 programs a binary zero into programmable counters 255 and 264. This results in these counters applying a logic high output to OR gates 257 and 266. The Ml control line output of ROM 241 enables AND gate 270 so that in the presence of a logic high on carry line 138 AND gate 270 allows frequency-variable weight-dependent transducer pulses to be applied to the countup input of counters 267 and 268 through AND gate 270, inverter 261 and AND gate 258. Counters 267 and 268 are now periodically reset by T. (reset) clock pulses during each compute interval by reason of AND gate 270 being enabled by the M2 output of ROM 241 through inverter 271. The T. (reset) clock pulses are applied through OR gate 269 to the counters.

When switch 94 is set to the SCALE position, a logic low is developed on control line Ml and a logic high is developed on control line M2. This causes AND gate 204 (Figure 11) to be enabled, allowing the f » wt. signals developed at the output of counter 102 to be applied through OR gate 204 to the display counter 202 of rate- derivation circuit 104. Since this counter continues to be latched and reset by T₂ and T. clock signals at one second intervals, counter 202 assumes a count proportional to the total weight of the collection container and the collected plasma. This count is displayed by rate display 93.

The SCALE position of switch 94 allows the operator to verify proper operation of the transducer circuits. Prior to performing a plasmapheresis procedure, the operator suspends a known weight from the transducer and compares the resulting reading on readout 93 with a reading known to be correct. If the two readings agree, the transducer is operating- properly.

Referring to Figure 20, the volume derivation, rate derivation and replacement ratio control circuits of collection monitor and replacement ratio control unit 22 may be incorporated with the replacement fluid pump 52 in a separate stand-alone collection monitor and replacement control apparatus 280. or use with existing blood fractionation filter and centrifugal-type systems (not shown). The apparatus may be housed in a housing 281 having a sloping top panel 283 on which the volume collected display 92, collection rate 'display 93, and atio/mode select switch 94 of the previously described plasmapheresis apparatus 20 are located. In addition, a replacement volume display 282 may be provided. The housing also includes a sloping bottom panel 284 on which the replacement pump 252 of the previously described apparatus is located.

- ^ξjRE OMPI_ A pair of vertical support poles 285 attached to the rear of the housing support a horizontal bar 286. The transducer circuit 100 is mounted on the horizontal bar to provide a signal having a voltage level proportional to weight on the transducer, as previously described. A cable 287 connects the transducer circuit to circuitry within housing 281.

The monitor and collection apparatus 281 may be utilized in either an exchange mode or in an autologous mode. In the exchange mode, a flow system 290 installed on the apparatus includes a tubing segment 291 which supplies plasma (or other blood fraction) separated in the associated fractionation apparatus to a collection container 292 suspend from the transducer*. As a volume of fluid in container 292 increases, replacement fluid is automatically pumped by replacement fluid pump 52 from a replacement fluid container 294 through a tubing segment 293 to the fractionation apparatus for recombination with the plasma-deficient blood and subsequent return to the donor.

In the autologous mode flow system 290 is configured as shown by the broken lines in Figure 18. Replacement fluid container 294 is not provided. Replacement fluid pump 52 pumps fluid from a second port on collection container 292 through tubing segment 293 to secondary treatment system 251, wherein the concentration of certain substances in the plasma may be attended by one or more processes.

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OMPI The processed plasma is returned to the fractionation apparatus by a tubing segment 295 for recombination and return to the donor.

As shown in Figure 21, the circuitry of apparatus may be similar to that of the pertinent portions of the processor unit 21 and the monitor and control unit 22 of plasmapheresis apparatus 20. The voltage-variable signal from transducer circuit 100 is converted to a f # wt. signal in conversion circuits 101 and applied to volume derivation circuit 103, wherein a volume collected output signal is developed for display 92, and collection pulses are developed for rate derivation circuit 104 and replacement control circuit 106. Rate derivation circuit 104 processes the collection pulses to provide a collection rate display 93. Replacement control circuits 106 compare the collection pulses with pulses from the tachometer 77 of replacement pump motor 76 and provide an analog output signal which controls the speed of motor 76 through motor control circuits 78 to maintain a ratio selected by switch 94. The output of tachometer 77 is also applied to replacement volume display 282 wherein a cumulative count is developed for display as total volume in milliliters of replacement fluid added. A ^' clock 115 provides necessary timing pulses for the various circuits of the apparatus.

Operation of apparatus 280 is coordinated with the operating mode of the associated fractionation apparatus by a control^*circuit 297, which receives over-limit signals from limit circuits 110 and 111 and a stall signal from motor control circuit 78, and provides an inhibit output to the motor control circuit and mode control signals to the other circuits. Stop, start and reset connections between control circuit 297 and the associated apparatus are provided through a connector 298.

In operation, apparatus 280 may be placed in any convenient location for connection to the fractionation apparatus. After the tubing and electrical connections have been made, operation is completely automatic; a predetermined volume ratio being maintained to the exchange mode, and a predetermined collected volume being maintained in the collection container in the autologous mode.

Thus, the invention provides a system for controlling the flow of replacement fluid for the blood fraction removed, and for maintaining an operator-selected ratio between the volume of fraction collected and the volume of fluid replaced. The selected ratio is _.maintained notwithstanding variations in plasma collection rate or disturbances to the plasma collection bag, thus avoiding the need for constant attention on the part of the operator and providing for more accurate control and monitoring of the fractionation process. Furthermore, the system includes internal safeguards

and alarms which alert the operator to malfunctions, and a system by which the operation and control of the associated processor apparatus is integrated with that of the monitor and control device. Additional features of the invention include the ability to operate in an autologous mode wherein a predetermined fluid level is maintained in the fraction collection bag, and in a scale mode wherein the actual weight of the collection bag and collected content may be readily determined. Furthermore, the invention may be provided in a stand-alone unit having a self-container replacement fluid pump for use in conjunction with a blood fractionation apparatus for monitoring the collection of a blood fraction or for adding replacement fluid to processed blood at an automatically maintained rate.

While the invention has been shown in conjunction with blood fractionation apparatus, it will be appreciated that the invention may be used in other applications and procedures where a ratio between a collected fluid and a replacement fluid are to be automatically maintained, or where a collected fluid component is to be removed from a collection container for processing concurrently with its collection in the container.

While particular embodiments of the invention have been shown and described it will be obvious to those skilled in the art that changes and modifications may be made therein without departing from the invention in its broader aspects, and, therefore, the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention.

Claims

CLAIMS :

1. In collection apparatus for collecting a fluid in a collection container, a collection monitor system comprising, in combination: an electrical strain transducer in supporting relationship to said container for providing an output signal having a frequency related to the weight of the collection container and the collected fluid'contained therein; and derivation means for automatically deriving from said transducer output signal collection signals indicative of incremental units of volume of the collected fluid added to the collection container; and volume indicator means responsive to said collection signals for providing an output indicative of the cumulative count of said incremental units, and hence the volume of fluid collected in the collection container.

2. A fluid collection apparatus as defined in claim 1 wherein said derivation means include comparison means for comparing the frequency of said transducer output signal over successive measurement intervals.

3. A fluid collection apparatus as defined in claim 1 wherein said apparatus has a maximum collection rate, and said volume indicator means are non-responsive to collection signals which exceed said maximum rate.

4. Fluid collection apparatus as defined in claim 1 wherein said volume indicator means comprise a counter for accumulating the sum of said collection signals.

5. Fluid collection apparatus as defined in claim 4 wherein said counter comprises a latch register and said volume indicator means include a digital display device connected to the output of said register.

6. A fluid collection apparatus as defined in claim 2 wherein said comparison means include a binary adder, and said volume indicator means include a display counter for receiving data from said adder.

7. A fluid collection apparatus as defined in claim 6 wherein said comparison means include parallel-to-serial signal conversion means for generating serial pulses indicative of the output of said binary adder, and wherein said pulses are applied to and counter by said display counter.

8. In a fluid collection apparatus for collecting a fluid in-a collection container, and of the type having a predetermined maximum collection rate and utilizing a disposable flow system having a collection chamber for the collected component, a collected volume display system comprising, in combination: an electrical strain transducer providing an output signal having a frequency related to the weight of the collection container and the collected blood fraction contained therein;

OMPI comparison means for repetitively comparing the -frequency of said transducer output signal over a present measurement interval with the frequency of said output signal over a preceding measurement interval to periodically develop a collection signal indicative of any change in units of volume collected during the measurement interval; volume indicator means including a display counter responsive to applied collection signals for providing an output indicative of the sum of said incremental units; and incrementing means for applying only collection signals indicating the collection of fluid increments which do not exceed the maximum collection rate to said counter whereby said indicator means indicate the volume of fluid collected in the collection container.

9. A fluid collection apparatus as defined in claim 8 wherein said incrementing means is inhibited for a predetermined period of time following said collection signal exceeding the maximum collection rate.

10. A fluid collection apparatus as defined in claim 8 wherein said comparison means include a binary adder, and said volume indicator means include a display counter for receiving data from said adder.

11.^* A fluid collection apparatus as defined in claim 10 wherein said comparison means include parallel-to-serial signal conversion means for generating serial collection pulses indicative of the output of said binary adder, and wherein said pulses are applied to and counted by said display counter.

12. A fluid collection apparatus as defined in claim 8 wherein said measurement intervals comprise one second.

13. In a fluid collection apparatus for collecting a fluid, and having a predetermined maximum collection rate and a disposable flow system having a collection container for the collected component, a collected volume display system comprising, in combination: an electrical strain transducer providing an output signal having a frequency related to the weight of the collection fluid contained therein; input counter means responsive to said transducer output signal for providing an output signal representative-of the frequency of said collection pulses; means for periodically applying said collection pulses to said input counter for a predetermined measurement interval to develop said output signal therein; storage means responsive to an applied control signal for storing said output signal subsequent to said measurement interval;

OMPI comparison means for comparing said output signal with said stored output signal in said storage means to develop a difference count indicative of increment volume units of fluid collected during the measurement interval; and volume indicator means responsive to said output signal for providing an output indicative of the cumulative count of said incremental units, and hence the volume of fluid collected.

14. A fluid collection apparatus as defined in claim 13 wherein said comparison means include a binary adder, and said volume indicator means include a display counter for receiving data from said adder.

15. A fluid collection apparatus as defined in claim 14 wherein said comparison means include parallel-to-serial signal conversion means for generating serial pulses indicative of the output of said binary adder, and wherein said pulses are applied to and counted by said display counter.

16. A fluid collection apparatus as defined in claim 13 wherein said volume indicator means is non-responsive to collection signals which exceed said maximum collection rate.

17. In a blood fractionation apparatus for separating and collecting a blood fraction from whole blood, and of the type having a predetermined maximum collection rate and utilizing a disposable flow system having a collection container for the collected component, a collected volume display system comprising, in combination: an electrical strain transducer in supporting relationship to the collection container providing an output signal having a frequency related to the weight of the collection container and the collected blood fraction contained therein, said weight pulses each corresponding to a unit of volume of the collected blood fraction; input counter means responsive to said transducer output signal for providing a first output- signal representative of the occurrence- of said weight pulses; means for periodically applying said weight pulses to said input counter for a predetermined measurement interval to develop said output signal therein; storage means responsive to an applied control signal for storing said output signal subsequent to said measurement interval; comparison means for comparing said output count with said stored count in said storage means to develop a difference signal indicative of volume units of the fraction collected during the measurement interval; and volume indicator means responsive to said output signal for providing an output indicative of the sum of said incremental units, and hence the volume of the blood fraction collected.

18. A blood fractionation apparatus as defined in claim 17 wherein said comparison means include a binary adder, and said volume indicator means include a display counter for receiving data from said adder.

19. A blood fractionation apparatus as defined in claim 18 wherein said comparison means include parallel-to-serial signal conversion means for generating serial pulses indicative of the output of said binary adder, and wherein said pulses are applied to and counter by said display counter.

20. A blood fractionation apparatus as defined in claim 17 wherein said volume indicator means is non-responsive to incremental collection signals which exceed maximum collection rate.

21. A blood fractionation apparatus as defined in claim 16 including means for enabling said storage means to assume the output count of said input counter only when said difference is less than the absolute of said maximum system collection rate.

22. In a fluid collection apparatus for collecting fluid in a collection container, a collection rate monitoring system comprising, in combination: means including an electrical strain transducer in supporting relationship to the collection container for providing collection signals indicative of the collection of volume increments of fluid in the collection container; and

OMPI rate derivation means for automatically deriving from said collection signals an output indicative of the rate of fluid collection in the collection container.

23. A fluid collection apparatus as defined in claim 22 wherein said collection signals comprise a series of collection pulses each representing a volume unit of collected fluid, and wherein said rate derivation means comprise a counter for accumulating said collection pulses over a predetermined period of time.

24. A fluid collection apparatus as defined in claim 23 wherein said rate derivation means derive said collection pulses over a series of discrete measurement intervals, a predetermined number of said measurement intervals comprising said predetermined unit of time, and wherein said counter accumulates only the most recent of said intervals.

25. A fluid collection apparatus as defined in claim 24 wherein said counter is a shift register.

26. In a fluid collection apparatus for collecting fluid in a collection container, a collection rate monitoring system comprising, in combination: means including an electrical strain transducer in supporting relationship to the collection container for providing an output signal having a frequency related to the weight of the collection chamber and the collected fluid contained therein;

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OMPI comparison means for repetitively comparing the-frequency of said transducer output signal over a measurement interval with the frequency of said output signal over an immediately preceding measurement interval to develop a collection signal indicative of the volume of fluid collected during the interval; accumulator means comprising a counter for developing the sum of said collection signals over a predetermined number of the most recent of said collection intervals corresponding to a unit of time; and rate derivation means for periodically developing from the sum of said incremental collection signals in said counter an output signal indicative of the collection rate.

27. A fluid collection apparatus as defined in claim 26 wherein said counter comprises a shift register.

28. A fluid collection apparatus as defined in claim 27 wherein said rate derivation circuit includes a display counter, and wherein data transfer means are provided for periodically transferring data in said shift register to said display counter.

29. A fluid apparatus as defined in claim

26 wherein said measurement intervals each comprise one second, said unit of time comprises one minute, and wherein sixty of said measurement intervals are summed by said counter.

30. A blood fractionation apparatus as defined in claim 26 wherein said rate derivation means develop said rate output after each of said measurement intervals.

31. In a fluid processing apparatus for separating, collection and replacing a fluid component in a whole fluid, and of the type utilizing a flow system having a collection container for the collected component, and a motor driven replacement fluid pump for adding replacement fluid to the depleted whole fluid, a control system for maintaining a predetermined ratio between the volume of fluid component collected and the volume of replacement fluid added, comprising, in combination: means including an electrical strain transducer in supporting relationship to the collection container for providing collection signals indicative of incremental units of volume of the collected component added to the collection container; first ratio circuit means responsive to said volume collection signal for providing a first comparison signal; means responsive to operation of said replacement fluid pump for providing an output signal indicative of the volume of replacement fluid added; second ratio circuit means responsive to said replacement fluid output signal for providing a second comparison signal; and

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OMPI comparison means for cumulatively comparing said first comparison signal with said second comparison signal to develop an output signal for controlling the speed of said replacement pump motor to maintain the predetermined volume ratio.

32. A fluid processing apparatus as defined in claim 31 wherein said collection signal comprises collection pulses, and said pump output'signal comprises tachometer pulses.

33. A fluid processing apparatus as defined in claim 32 wherein said first and second ratio multiplier circuits comprise programmable counters.

34. A fluid processing apparatus as defined in claim 33 including a user-operated ratio selection switch, and a read only memory responsive to the setting of said selector switch for providing ratio-determining control signals to said programmable counters.

35. A fluid processing apparatus as defined in claim 31 wherein said comparison means comprise an up-down counter.

36. A fluid processing apparatus as defined in claim 35 wherein said comparison means further comprise a binary-to-analog converter, and wherein said up-down counter provides an output signal for application to said converter, said converter provides said pump motor control signal, and said control signal comprises an analog signal.

37. A fluid processing apparatus as defined in claim 35 including limit means providing an alarm output upon said up-down counter exceeding a predetermined maximum count.

38. A fluid fractionation system for use in conjunction with a secondary processing system for separating, collection, processing and returning a fluid fraction from continuously supplied whole fluid, comprising: a flow system including means for separating the fluid fraction, a collection container for the separated fraction, and recombination means for introducing the processed fraction back into the processed fluid; and means including a motor-driven pump for pumping collected fraction from said container to said secondary processing system, and processed fraction from said system to said recombination means.

39. A fluid fractionation system as defined in claim 38 including flow control means for maintaining a substantially constant volume of collected fraction in said collection container.

40. A fluid fractionation system as defined in claim 39 wherein said flow control means include a motor control means responsive to the volume in said collection container for controlling said pump motor to maintain said constant volume.

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41. A fluid fractionation system as defined in claim 40 wherein said motor control means include an electrical strain-gauge transducer supportively coupled to said collection container for producing an output signal indicative of the weight of the container and the collection fraction continued therein.

42. A fluid fractionation system for use in conjunction with a secondary processing system for separating, collecting, processing and returning a fluid fraction from continuously supplied fluid, comprising: a flow system including means for separating the fluid fraction, a collection container for the separated fraction, and recombination means for introducing the processed fraction back into the processed fluid; means including a motor-driven pump for pumping collection fraction from said container to said secondary processing system, and processed fraction from said system to said recombination means; means including an electrical strain-gauge transducer supportively engaged to said collection container for producing an output signal dependent on the weight of the collection container and the collected fraction therein; and motor control circuit means responsive to said output signal for controlling the operation of said pump motor to maintain a substantially constant volume in said collection container.

43. A fluid fractionation system as defined in claim 42 wherein said motor control circuit means include means for storing a level of said output signal, and means for comparing the present signal level with the stored signal level to develop a motor control signal.

44. A fluid fractionation system as defined in claim 43 wherein the operating speed of said pump motor increases with the difference between said stored level and said present output signal level.

45. A fluid fractionation system as defined in claim 44 wherein said motor control means include means for developing the difference between said stored level and said present level to produce said motor control signal.

46. In a fluid processing apparatus for separating, collecting and returning a fluid component in a whole fluid, and of the type utilizing a flow system having a collection container for the collected component, and a motor driven replacement pump for removing fluid from the collection container for processing and recombination with the depleted fluid, a control system comprising, in combination: equilibrium circuit means including an electrical strain transducer in supporting relationship to the collection container for providing an output signal indicative of the weight of the container and the fluid contained therein being above a reference weight, and motor control means responsive to said output signal for causing and replacement motor to operate to withdraw fluid from the container for processing and recombination with the whole fluid while maintaining a substantially constant volume of collected fluid in the collection container.

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