Method and apparatus for continuous plasmapheresis

Abstract

A process and apparatus are provided for continuously separating blood into plasma and cellular component fractions and returning the latter to the subject in admixture with a makeup fluid. The separation is effected by continuously ultrafiltering the subject's blood at specified shear stresses and pressures employing a membrane ultrafilter, preferably having a pore size of 0.45 microns, and a disclosed flow system.

We claim: 
     
       1. An apparatus for the continuous separation of blood into a cellular component fraction and a plasma fraction comprising: (a) an ultrafiltration cell comprising a filter membrane having a pore size of from about 0.1 to about 1.0 microns in diameter, said membrane separating said cell into filtering and filtrate chambers, said filtering chamber comprising an inlet and an outlet, and said filtrate chamber comprising an inlet and an outlet;   (b) a blood input pumping means for pumping blood directly from a blood vessel to the inlet of said filtering chamber and delivering a flow of whole blood parallel to said filter membrane in depths of from about 0.1 mm to about 1.0 mm measured perpendicularly from the face of said membrane, and at rates sufficient to obtain a shear rate at the membrane interface of from about 10 dynes/cm 2  to about 1000 dynes/cm 2  ;   (c) a pumping means to direct a portion of said plasma fraction flowing from the outlet of said filtrate chamber in a flow from the inlet to the outlet of said filtrate chamber and parallel and in the same direction as the flow of whole blood passing through said filtering chamber.   
     
     
       2. The apparatus of claim 1 and further comprising recycle pumping means connected between the input and output of said filtering chamber for recycling a portion of the cellular component fraction from the outlet of said filtering chamber to the inlet of said filtering chamber to obtain the desired shear rate within said filtering chamber at whole blood flow rates which are not great enough to provide said shear rates. 
     
     
       3. The apparatus of claim 1 and further comprising a plasma pumping means connected to the outlet of said filtrate chamber. 
     
     
       4. The apparatus of claim 3 and further comprising pressure sensing means connected between the outlet of said filtrate chamber and said plasma pumping means for sensing the pressure in said filtrate chamber. 
     
     
       5. The apparatus of claim 4 and further comprising pressure regulating means interconnected to said pressure sensing means and said plasma pumping means for regulating the operation rate of said plasma pumping means in response to variations of filtrate chamber pressures as sensed by said pressure sensing means. 
     
     
       6. The apparatus of claim 3 and further comprising replacement fluid pumping means connected to the inlet of said filtering chamber for delivering a volume of replacement fluid to said filtering chamber at volumetric rates substantially equal to the volume of plasma fraction leaving said filtrate chamber. 
     
     
       7. The apparatus of claim 6 wherein said replacement fluid pumping means and said plasma pumping means are interconnected so as to operate at substantially the same rate and thereby provide for the addition of a replacement fluid to said filtering chamber at the same rate as the plasma fraction is being removed from said filtrate chamber by said plasma pump. 
     
     
       8. The apparatus of claim 1 and further comprising drip cell means for removing entrapped gases from the blood being separated, a first said drip cell means communicating with the inlet of said filtering chamber and a second drill cell means communicating with the outlet of said filtering chamber. 
     
     
       9. The apparatus of claim 8 and further comprising pressure indicating means, a first said pressure indicating means communicating with the inlet of said filtering chamber and a second said pressure indicating means communicating with the outlet thereof. 
     
     
       10. The apparatus of claim 1 and further comprising pressure indicating means communicating with the inlet of said filtrate chamber. 
     
     
       11. The apparatus of claim 1 and further comprising flow restriction means communicating with the outlet of said filtering chamber for regulating the rate of flow from said outlet and thereby the pressure within said filtering chamber. 
     
     
       12. The apparatus of claim 1 wherein said filter membrane has a pore size of about 0.45 microns and is fabricated from materials selected from the group consisting of cellulose nitrate and regenerated cellulose. 
     
     
       13. An apparatus for the continuous separation of blood into a cellular component fraction and a plasma fraction comprising: (a) an ultrafiltration cell comprising a filter membrane having a pore size of from about 0.1 to about 1.0 microns in diameter separating said cell into filtering and filtrate chambers, said filtering chamber having an inlet and an outlet and said filtrate chamber having an outlet;   (b) blood input pumping means for pumping blood directly from a blood vessel to the inlet of said filtering chamber and delivering a flow of whole blood parallel to said filter membrane in depths of from about 0.1 mm to about 1.0 mm, measured perpendicularly from the face of said membrane;   (c) recycle pumping means connected between the inlet and outlet of said filtering chamber for recycling a portion of said blood fraction from said outlet to said inlet the combined flow rates of said o the outlet of said filtrate chamber for removing said plasma fraction from said filtrate chamber;   (e) replacement fluid pumping means connected to the inlet of said filtering chamber for delivering replacement fluid thereto at substantially the same volumetric rate at which said plasma fraction is being removed from said filtrate chamber via said plasma pumping means.   
     
     
       14. The apparatus of claim 13 and further comprising pressure sensing means connected between the outlet of said filtrate chamber and said plasma pumping means for sensing pressure in said filtrate chamber, and automatic pressure regulating means interconnected between said pressure sensing means and said plasma pumping means for regulating the pumping rate of said pumping means in response to variations in pressure sensed by said pressure sensing means. 
     
     
       15. The apparatus of claim 13 wherein said replacement fluid pumping means and said plasma pumping means are interconnected so as to operate at substantially the same rate to thereby provide for delivery of replacement fluid to said filtering chamber at the same volumetric rate at which said plasma fraction is removed from said filtrate chamber. 
     
     
       16. The apparatus of claim 13 and further comprising drip cell means for removing entrapped gas in blood being separated, a first drip cell means communicating with the inlet of said filtrate chamber and a second drip cell means communicating with the outlet thereof. 
     
     
       17. The apparatus of claim 16 and further comprising pressure indicating means, a first said pressure indicating means communicating with the inlet of said filtering chamber and a second said pressure indicating means communicating with the outlet of said filtering chamber. 
     
     
       18. The apparatus of claim 13 wherein said filter membrane has a pore size of about 0.45 microns and is fabricated from materials selected from the group consisting of cellulose nitrate and regenerated cellulose. 
     
     
       19. A continuous plasmapheresis process comprising: (a) continuously withdrawing whole blood from the blood vessel of a donor and pumping said whole blood into the filtering chamber of an ultrafiltration cell;   (b) continuously filtering said whole blood into a cellular component fraction and a plasma fraction by passing it in a flow over and parallel to an ultrafilter membrane having a pore size of from about 0.1 to 1.0 microns in diameter, and at a flow rate sufficient to provide a shear stress at the membrane interface of from about 10 dynes/cm 2  to about 1000 dynes/cm 2  at transmembrane pressures of from about 50 mm of mercury to about 700 mm of mercury;   (c) continuously admixing said cellular component fraction with an amount of replacement fluid substantially equal to said separated plasma fraction; and   (d) continuously returning said cellular component fraction and replacement fluid mixture to a blood vessel of said donor.   
     
     
       20. The process of claim 19 and further comprising recycling a portion of the plasma fraction separated from said whole blood in a flow parallel to and in the same direction as the flow of said whole blood over said ultrafilter membrane, but on the opposite side of said membrane from the flow of whole blood, to thereby obtain a substantially uniform transmembrane pressure across the entire length of said membrane. 
     
     
       21. The process of claim 19 and further comprising recycling a portion of said cellular component fraction over said ultrafilter membrane in the same direction as said flow of whole blood in a manner such that said shear rates can be obtained at insufficient whole blood flow rates. 
     
     
       22. The process of claim 19 wherein said transmembrane pressure is from about 100 to about 400 mm of mercury. 
     
     
       23. The process of claim 19 wherein said ultrafiltration is effected employing an ultrafilter membrane having a pore size of about 0.45 microns and fabricated from materials selected from the group consisting of cellulose nitrate and regenerated cellulose. 
     
     
       24. The process of claim 19 wherein said shear stress at the membrane interface is from about 150 dynes/cm 2  to about 600 dynes/cm 2 . .Iadd. 25. Apparatus for plasmapheresis treatment of a patient, comprising: (a) an ultrafiltration cell having an inlet for receiving a flow of whole blood, an outlet for discharging blood cellular components, and an outlet for discharging plasma filtrate;   (b) means disposed in said ultrafiltration cell for effecting separation of plasma and cellular components of whole blood flowing therein;   (c) means for continuously withdrawing whole blood from a blood vessel of a patient and supplying same to the whole blood inlet of said cell;   (d) means coupled to the blood cellular components outlet, for continuously receiving the separated blood cellular components and supplying same back to the patient; and   (e) means coupled to the plasma filtrate outlet, for continuously removing plasma filtrate therefrom. .Iaddend..Iadd. 26. The apparatus of claim 25 further comprising:   means in fluid communication with the whole blood inlet to said cell, for supplying a continuous flow of replacement fluid to be admixed with whole blood incoming to the whole blood inlet. .Iaddend. .Iadd. 27. Apparatus for plasmapheresis treatment of a patient, comprising:   (a) an ultrafiltration cell having a filter membrane defining filtering and filtrate chambers, said filtering chamber having an inlet and an outlet, and said filtrate chamber having an outlet unconnected with the filtering chamber outlet;   (b) means for continuously withdrawing whole blood from a blood vessel of a patient and supplying same to the filtering chamber inlet, and establishing a parallel flow across said filter membrane at a rate sufficient to produce a shear rate at the membrane interface that effects separation of plasma and blood cellular components without hemolysis;   (c) means coupled to the filtering chamber outlet, for continuously receiving the separated blood cellular components and supplying same back to the patient; and   (d) means coupled to the filtrate chamber outlet, for continuously removing the separated plasma fraction from the filtrate chamber. .Iaddend..Iadd. 28. The apparatus of claim 27 further comprising:   means in fluid communication with the filtering chamber inlet, for supplying a continuous flow of replacement fluid to be admixed with whole blood incoming to the filtering chamber. .Iaddend.