CA1185218A - Centrifugal separation of platelet rich plasma - Google Patents
Centrifugal separation of platelet rich plasmaInfo
- Publication number
- CA1185218A CA1185218A CA000376843A CA376843A CA1185218A CA 1185218 A CA1185218 A CA 1185218A CA 000376843 A CA000376843 A CA 000376843A CA 376843 A CA376843 A CA 376843A CA 1185218 A CA1185218 A CA 1185218A
- Authority
- CA
- Canada
- Prior art keywords
- chamber
- bag
- cavity
- blood sample
- blood
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/16—Blood plasma; Blood serum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D43/00—Separating particles from liquids, or liquids from solids, otherwise than by sedimentation or filtration
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/491—Blood by separating the blood components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0442—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
- B04B2005/0471—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation with additional elutriation separation of different particles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0442—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
- B04B2005/0485—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation with a displaceable piston in the centrifuge chamber
Abstract
ABSTRACT
This invention relates to a method and apparatus for separating platelets from blood samples by subjecting the blood sample to centrifugal force in the chamber while displacing the platelets from the blood sample by injecting a relatively small volume of saline into the centrifugally outer end of the chamber. In the preferred apparatus, the saline is injected into the blood sample by driving the chamber supporting the blood sample against a saline filled collapsible cavity under the influence of centrifugal force.
This invention relates to a method and apparatus for separating platelets from blood samples by subjecting the blood sample to centrifugal force in the chamber while displacing the platelets from the blood sample by injecting a relatively small volume of saline into the centrifugally outer end of the chamber. In the preferred apparatus, the saline is injected into the blood sample by driving the chamber supporting the blood sample against a saline filled collapsible cavity under the influence of centrifugal force.
Description
The invent:ion pertains broadly to centri~ugal separation of finely dlvlded solid particles. More particularl~, the invention relates to a new pro-cess and a device for centrifugal separation of solid particles dissimilar in size and/or density, such as platelets and other blood cells or various types of s~nthetic particles and beads.
The art of separating finely divided dissimilar solid particles is largel~ based on differential sedimentation by centrifugation. The main problems inherent in this process are partial trapping of small particles by large ones and a lack of a sharp end point of separation during sedimentation. This con-fronts the users with a compromising situation where in order to increase the yield o:E separated particles, their purit~ will decrease and vice versa.
Transfusion of platelets is now a widely used form of therapy for the treatment of hemorrhage in thrombocytopenic and thromboc~topathic patients. It is indispensable in the protocol treatment programs for acute leukemia, aplastic anemia, platelet deficiency, as well as replacement therapy in major surgical procedures.
Platelets are separated from whole blood as platelet-rich plasma ~PRP) by procedures involving centri-Eugation. Transfusion of platelets is accomplished most often in a form of platelet-concentrates ~PC) which are prepared by the high speed centrifugation of PRP. Several units of blood are required to obtain a sufficient number of platelets for therapeutic effectiveness. The use of multiple donors increases risks of isoimmunization and transmission of disease.
In order to procure enough platelets from a single donor, the technique o:E
plasmapheresls is required in which platelet-poor plasma ~PPP) and packed red blood cells (RBC~ are returned to the donor's blood circulation The commonly used procedure of slow speed centrifugation with the routine equipment Eound in any blood bank is cumbersome, vary time-consuming, and ylelds platelets heavily contaminated WIt]~ wh:ite ~lood cells (WBC) and ~BCs and gavc low pla~elet re-covery. A considerable improvement in the procurement of plate]ets has been made by the use of specialized blood processing equipment, ~laemonetics-30, which permits the collection of two to four units of PC from a single donor. In this procedure, known as plateletpheresis, blood is pumped directly rom the donor through a rotary seal into a centrifuge plastic bowl. Blood components are separated by forming concentric bands which overflow from the bowl in a sequenca, dçpending on their specific density. This teclmique, however, permits one to harvest on the average only 46 percent of platelets from the blood circulating in the bo~l. In order to collect the ~ x 1011 platelets required for therapeuti-cally effective transfusion, at least 6 liters of blood must be processed, which ta~es from 2 to 3 hours of the donor's time. The opcration is time-consuming and costly. Also, large initial investment for purchasing expensive equipment is requlred. Collected with this technique, platelets are heavily contaminated with WBCs and RBCs. Administration of PC contaminated with WBC may cause serious complications in patients. Platelets and WBC share HL-A antigens which are more immunogenic on WBC than those on platelets. As a result, WBC contamination may be responsible for the alloimmunization in patients which, in turn, causes with each consecutive transfusion progressive reduction in hemostatic effectiveness of platelets and, in more severe cases, may lead to post-transfusion thrombocy-topenia. There are a]so systemic reactions which may occur within 20 minutes after completion of a platelet transfusion consisting of chills and fever. Anti-bodies to contaminating leucocytes are implicated in these reactions. Because o~ these side effects, removal of contaminating WBCs from PC by differential centrifugation is strongly recommended, which further complicates the procedure.
Clearly, there is a need for improvement of platelet collection technique by making it safer and more effective in collecting PC a-t a higher yield, free of 5~
~B~ and involving shortcr ~ime and lower cost than the present techniques offered.
Bearing the above in mind, it is an object of the present invention to provide a new process and a device for the separation of finely divided solid particles dissimilar in si~e and/or density while allowing both high yield and purity of the separated particles. In order to accomplish this object, the ex-isting process and system known as counterflow centrifugation ~CC~ or centrifugal elutrlation ~CE) have been substantiall~ modified to adapt both of them for this new use.
In tlle CE process and system, developed by Beckman Company, the separa-tion of particles is accomplished in a separation chamber ~ithln the ElutriatGr rotor. The tendency of particles to sediment in a centrifugal field is balanced in the cham~er ~y a liquid flow in the opposite direction. By increasing the flow rate, smaller particles are washed out while larger or denser particles remain in the chamber. To accomplish ~he separation of particles, a large volume of liquid is- made to pass through the separation chamber at a relatively high flow rate. Pumping of liquid into the rotor and through the separation chamber is accomplished by means of a rotary seal. Although both the Beckman system and their procedure are being successfully used for the separation of such blood 2Q cells as granulocytes, monocytes and young red cells, both of them are not suit-able for th0 separation of platelets.
The object of this invention is to provide both a new design of the separation chamber effective for separation of widely dissimilar particles such as platelets and other blood cells and a new procedure for the accomplishment of the above goal. Based on an experimental study of chambers with different con-f~gurations, the one with a conical shapc and larger in volume than the Bcckman cham~er, being 10.5 ml instead of 4.5 ml, was found to be most suitable for platelet separation. The reasons for this are that the conical chamber with about a 40 angle at its taper provides a steep and uniform fluid velocity gradi-ent, directed against the centrifugal force gradient, thereby allowing one to keep blood cells in the chamber at a steady state equilibrium as a dense cell suspension with a sharp upper boundary which bears physical characteristics of a fluid~zed bed of particles. This fluidized bed of blood cells acts as a depth filter allowing platelets to pass through freely while retaining all other blood cells in the chamber. An important difference in thls procedure from that of Beckman is that a ver~ low flow rate of 3.5 ml~min and a small volume of medium lQ of 5 to 8 ml are required for the separation of platelets, while for the separa-tion of other blood cells by Beckman's CE procedure, flow rates from 15 to 25 ml/min and volumes of medium -from 700 to 1000 ml are required. Also, separation of platelets by this process requires about two minutes for its completion while the separation of other blood cells requires from 40 to 60 minutes. As a resu~t, the separation procass in the present invention can be characterized as a dis-placement process combined with the filtration in which a small volume of saline rapidly displaces PRP from whole blood. In contrast, cell separation by the CE
process involves velocity sedimentation by washing with large volumes of medium.
The supporting experimental evidence for the existence of the filtration action in such a fluidized bed of blood cells contained in the separation chamber is provided by unsuccessful attempts to remove the RBCs and WBCs contaminations from the PRP preparations collected by ~he Haemonetics-30 blood processor. Apparently, presence of a much lower number of blood cells in this PRP preparation, as com-pared to that with whole blood, did no~ permit attainment of the self-stabilizing and filtering action by the fluidized bed of blood cells, which resulted in the displacement of a large number of RBCs and WBCs together with PRP.
~ore particularly, it is an object to provide a new method for effective ~qL ;~
separation of PRP -Erom whole blood, by preloading the separation chamber wi~h blood outside the rotor rather than loading the chamber during centrifugation as in Beckman's procedure. Beckman's procedure for the loadlng of blood was found totally inadequate ~or the separation of platelets because it Erequently caused packing of blood cells, resulting in blood hemolysis accompanied by release of ADP. The latter apparently causes platelets to aggregate which, ln turn, pre-vents thelr separation. By preloading the chamber with blood this problem is completely eliminated.
A ~urther ob~ject in this new procedure is to allow initial clearance at the top of the chamber from blood cells by centrifugation from one minute without starting the counterflow of saline. This prevents an immediate elution of blood cells from the top of the chamber which would otherwise contaminate the exit line and prevent the collection of pure PRP.
Another object of this invention is to provide a self-contained system for the separation o~ dissimilar solid particles without involving the use of the Bec~man Elutriator rotor. This is accomplished by replacing the Beckman external pumping system by an internal one using a piston pump incorporated into the unit conta~ning the chamber. This unit is used as an insert in a centrifuge equipped with swinging buckets. The pump in the unit is energized by centrifugal force 2Q and provides the necessary fluid flow within the separation chamber directed against centrifugal force. The flow rate is controlled by a needle valve.
The invention provides apparatus for separating solid particles such as platelets from a liquid sample such as blood comprising (a) a body adapted to be subjected to centrifugal force and containing a cavi~ty to receive a volume of displacing liquid therein, (b~ a piston mounted in the body for movement into the cavity in response to centrifugal ~orce on the piston with the piston containing a centrifugal charnber having inner and ou-ter ends ancl adapted to receive the sample from whlch particles are to be separated, and i.njection passageway means for move-ment of displacing liquid from the cavity to the centrifugal outer end of the chamber in response to movement of the pis-ton into the cavity, (c) a discharge passageway at the centrifugally inner end of the chamber for discharging particle rich liquid in response to injection of dis-placing liquid into the chamber, and (d) means for preventing flow of displacing liquid from the cavity to the chamber before centrifugal stratification of blood cells in the chamber.
The invention also provides the me-thod o-E separating platelets from a blood sample comprising:
(a) supporting the blood sample in a centrifugal chamber having inner and outer ends, (b) subjecting a chamber to an initial centrifugal force of at least a predetermined minimum to stratify red cells in the sample away from the inner end, and (c) subjecting the chamber to a second centrifugal force while (1) injecting into the outer end of the chamber from a cavity a displacing liquid having a volume of between 0.2 and two times the volume of plasma in the sample at a flow rate less than out 1.0 ml. per minute per ml. of the blood sample, and
The art of separating finely divided dissimilar solid particles is largel~ based on differential sedimentation by centrifugation. The main problems inherent in this process are partial trapping of small particles by large ones and a lack of a sharp end point of separation during sedimentation. This con-fronts the users with a compromising situation where in order to increase the yield o:E separated particles, their purit~ will decrease and vice versa.
Transfusion of platelets is now a widely used form of therapy for the treatment of hemorrhage in thrombocytopenic and thromboc~topathic patients. It is indispensable in the protocol treatment programs for acute leukemia, aplastic anemia, platelet deficiency, as well as replacement therapy in major surgical procedures.
Platelets are separated from whole blood as platelet-rich plasma ~PRP) by procedures involving centri-Eugation. Transfusion of platelets is accomplished most often in a form of platelet-concentrates ~PC) which are prepared by the high speed centrifugation of PRP. Several units of blood are required to obtain a sufficient number of platelets for therapeutic effectiveness. The use of multiple donors increases risks of isoimmunization and transmission of disease.
In order to procure enough platelets from a single donor, the technique o:E
plasmapheresls is required in which platelet-poor plasma ~PPP) and packed red blood cells (RBC~ are returned to the donor's blood circulation The commonly used procedure of slow speed centrifugation with the routine equipment Eound in any blood bank is cumbersome, vary time-consuming, and ylelds platelets heavily contaminated WIt]~ wh:ite ~lood cells (WBC) and ~BCs and gavc low pla~elet re-covery. A considerable improvement in the procurement of plate]ets has been made by the use of specialized blood processing equipment, ~laemonetics-30, which permits the collection of two to four units of PC from a single donor. In this procedure, known as plateletpheresis, blood is pumped directly rom the donor through a rotary seal into a centrifuge plastic bowl. Blood components are separated by forming concentric bands which overflow from the bowl in a sequenca, dçpending on their specific density. This teclmique, however, permits one to harvest on the average only 46 percent of platelets from the blood circulating in the bo~l. In order to collect the ~ x 1011 platelets required for therapeuti-cally effective transfusion, at least 6 liters of blood must be processed, which ta~es from 2 to 3 hours of the donor's time. The opcration is time-consuming and costly. Also, large initial investment for purchasing expensive equipment is requlred. Collected with this technique, platelets are heavily contaminated with WBCs and RBCs. Administration of PC contaminated with WBC may cause serious complications in patients. Platelets and WBC share HL-A antigens which are more immunogenic on WBC than those on platelets. As a result, WBC contamination may be responsible for the alloimmunization in patients which, in turn, causes with each consecutive transfusion progressive reduction in hemostatic effectiveness of platelets and, in more severe cases, may lead to post-transfusion thrombocy-topenia. There are a]so systemic reactions which may occur within 20 minutes after completion of a platelet transfusion consisting of chills and fever. Anti-bodies to contaminating leucocytes are implicated in these reactions. Because o~ these side effects, removal of contaminating WBCs from PC by differential centrifugation is strongly recommended, which further complicates the procedure.
Clearly, there is a need for improvement of platelet collection technique by making it safer and more effective in collecting PC a-t a higher yield, free of 5~
~B~ and involving shortcr ~ime and lower cost than the present techniques offered.
Bearing the above in mind, it is an object of the present invention to provide a new process and a device for the separation of finely divided solid particles dissimilar in si~e and/or density while allowing both high yield and purity of the separated particles. In order to accomplish this object, the ex-isting process and system known as counterflow centrifugation ~CC~ or centrifugal elutrlation ~CE) have been substantiall~ modified to adapt both of them for this new use.
In tlle CE process and system, developed by Beckman Company, the separa-tion of particles is accomplished in a separation chamber ~ithln the ElutriatGr rotor. The tendency of particles to sediment in a centrifugal field is balanced in the cham~er ~y a liquid flow in the opposite direction. By increasing the flow rate, smaller particles are washed out while larger or denser particles remain in the chamber. To accomplish ~he separation of particles, a large volume of liquid is- made to pass through the separation chamber at a relatively high flow rate. Pumping of liquid into the rotor and through the separation chamber is accomplished by means of a rotary seal. Although both the Beckman system and their procedure are being successfully used for the separation of such blood 2Q cells as granulocytes, monocytes and young red cells, both of them are not suit-able for th0 separation of platelets.
The object of this invention is to provide both a new design of the separation chamber effective for separation of widely dissimilar particles such as platelets and other blood cells and a new procedure for the accomplishment of the above goal. Based on an experimental study of chambers with different con-f~gurations, the one with a conical shapc and larger in volume than the Bcckman cham~er, being 10.5 ml instead of 4.5 ml, was found to be most suitable for platelet separation. The reasons for this are that the conical chamber with about a 40 angle at its taper provides a steep and uniform fluid velocity gradi-ent, directed against the centrifugal force gradient, thereby allowing one to keep blood cells in the chamber at a steady state equilibrium as a dense cell suspension with a sharp upper boundary which bears physical characteristics of a fluid~zed bed of particles. This fluidized bed of blood cells acts as a depth filter allowing platelets to pass through freely while retaining all other blood cells in the chamber. An important difference in thls procedure from that of Beckman is that a ver~ low flow rate of 3.5 ml~min and a small volume of medium lQ of 5 to 8 ml are required for the separation of platelets, while for the separa-tion of other blood cells by Beckman's CE procedure, flow rates from 15 to 25 ml/min and volumes of medium -from 700 to 1000 ml are required. Also, separation of platelets by this process requires about two minutes for its completion while the separation of other blood cells requires from 40 to 60 minutes. As a resu~t, the separation procass in the present invention can be characterized as a dis-placement process combined with the filtration in which a small volume of saline rapidly displaces PRP from whole blood. In contrast, cell separation by the CE
process involves velocity sedimentation by washing with large volumes of medium.
The supporting experimental evidence for the existence of the filtration action in such a fluidized bed of blood cells contained in the separation chamber is provided by unsuccessful attempts to remove the RBCs and WBCs contaminations from the PRP preparations collected by ~he Haemonetics-30 blood processor. Apparently, presence of a much lower number of blood cells in this PRP preparation, as com-pared to that with whole blood, did no~ permit attainment of the self-stabilizing and filtering action by the fluidized bed of blood cells, which resulted in the displacement of a large number of RBCs and WBCs together with PRP.
~ore particularly, it is an object to provide a new method for effective ~qL ;~
separation of PRP -Erom whole blood, by preloading the separation chamber wi~h blood outside the rotor rather than loading the chamber during centrifugation as in Beckman's procedure. Beckman's procedure for the loadlng of blood was found totally inadequate ~or the separation of platelets because it Erequently caused packing of blood cells, resulting in blood hemolysis accompanied by release of ADP. The latter apparently causes platelets to aggregate which, ln turn, pre-vents thelr separation. By preloading the chamber with blood this problem is completely eliminated.
A ~urther ob~ject in this new procedure is to allow initial clearance at the top of the chamber from blood cells by centrifugation from one minute without starting the counterflow of saline. This prevents an immediate elution of blood cells from the top of the chamber which would otherwise contaminate the exit line and prevent the collection of pure PRP.
Another object of this invention is to provide a self-contained system for the separation o~ dissimilar solid particles without involving the use of the Bec~man Elutriator rotor. This is accomplished by replacing the Beckman external pumping system by an internal one using a piston pump incorporated into the unit conta~ning the chamber. This unit is used as an insert in a centrifuge equipped with swinging buckets. The pump in the unit is energized by centrifugal force 2Q and provides the necessary fluid flow within the separation chamber directed against centrifugal force. The flow rate is controlled by a needle valve.
The invention provides apparatus for separating solid particles such as platelets from a liquid sample such as blood comprising (a) a body adapted to be subjected to centrifugal force and containing a cavi~ty to receive a volume of displacing liquid therein, (b~ a piston mounted in the body for movement into the cavity in response to centrifugal ~orce on the piston with the piston containing a centrifugal charnber having inner and ou-ter ends ancl adapted to receive the sample from whlch particles are to be separated, and i.njection passageway means for move-ment of displacing liquid from the cavity to the centrifugal outer end of the chamber in response to movement of the pis-ton into the cavity, (c) a discharge passageway at the centrifugally inner end of the chamber for discharging particle rich liquid in response to injection of dis-placing liquid into the chamber, and (d) means for preventing flow of displacing liquid from the cavity to the chamber before centrifugal stratification of blood cells in the chamber.
The invention also provides the me-thod o-E separating platelets from a blood sample comprising:
(a) supporting the blood sample in a centrifugal chamber having inner and outer ends, (b) subjecting a chamber to an initial centrifugal force of at least a predetermined minimum to stratify red cells in the sample away from the inner end, and (c) subjecting the chamber to a second centrifugal force while (1) injecting into the outer end of the chamber from a cavity a displacing liquid having a volume of between 0.2 and two times the volume of plasma in the sample at a flow rate less than out 1.0 ml. per minute per ml. of the blood sample, and
(2) displacing platelet rich plasma from the inner end of the chamber at sub-stantially the same volume and rate, with the displacing liquid ejected from the cavi ky by the second centrifugal force on the blood sampl.e.
The invention further provides a triple bag adapted to be received in a cen-trifugal apparatus for separating platelet rich plasma from a blood sample comprising:
. ~. (a) a central portion having a generally conical shape with a centrifugal.ly outer end at the ver-tex oE -the cone and a cen-trifugal]y inner end at the opposite end thereof and adap-ted to Gontain the blood sample, (b) a collapsible injection por-tion adapted to contain a volume of saline less than the volume of the central portion of the bag and communicating wi-th the centrifugally ou-ter end of the central portion for injecting saline into the central portion as the injection portion collapses, and (c) an expandable collection portion communicating with -the centrifugally inner end of the central portion for collecting platelet rich plasma displaced from the central portion.
The separation of dissimilar solid particles, such as platelets and other blood cells, is effected by holding red and white blood cells with the aid of centrifugal force at a steady state equilibrium in the chamber, preferably of a conical shape, while displacing platelet rich plasma (PRP) with an equivalent volume of normal saline which is filtering through the suspension of blood cells in the direction generally against the centrifugal force. 'I'he liquid medium en-ters the conical chamber at its vertex which is oriented away from the center of rotation, thereby being at the centrifugal ou-ter end of the chamber, while PRP
exits the chamber through its base, which is the centrifugal inner end of the chamber. The liquid flow is generated by means of a piston pump in response to centrifugal force, the apparatus is preferably designed as an insert to be used in a centrifuge swin~ing bucket, and consists of a cylinder and a piston, the latter incorporating both the conical separation chamber at its lower end and the PRP receiving chamber at its upper end. 'l'here is a needle valve in the piston controlling the flow rate of the medium flowing from the cylinder through -the passageway leading to the conical chamber's centrifugal outer end. To prevent an im~nediate discharge of blood cells from the conical chamber by the flow of saline at the start of centrifugation, a control means is provided for holding movement of the piston lnto the cylinder until a maximum centrifugal force is applied. The control means may comprise an o-ring on the piston received iTI a groove in the wall o~ the cylinder. This provision allows one to clear blood cells from the centripetal end of the chamber ~y sedimenting cells at a low centrifugal speed applied for one minute after which centrifugal speed is raised to a required higher value at which the o-ring snaps from the groove and the piston begins to force medium from the cylinder into the conical chamber.
Disclosed herein is a self-contained s~stem, as described above, for the efective collection of PRP from whole blood, prefe~ably from the same donor, lQ free of other blood cells and in a quantity and quality compatible with the re-quirements practiced in blood banks and in hospitals. The totally sealed, dis-posable, low-cost system consist o three interconnected collapsible plastic bags, held together in a rigid support which is fitted into a centrifuge bucket.
~ore particularly, the system o~ three bags consists of the middle bag, prefer-abl~ conical in shape, filled with blood and functioning as a separation chamber;
the lower bag holding normal saline for displacement of PRP from the middle bag;
and the upper bag for receiving PRP displaced from the middle bag. ~lso~ the system ;s sterile and incorporates the means for aseptic handling during all the procedural steps.
2Q ~eferring now to the accompanying drawings:
Pigure 1 is a vertical section of the scaled-up version of the appara-tus taken along the vertical central axis and showing the apparatus consisting of - tnree cGllaps~ible bags inserted into the centrlfuge bucket.
Fi~gure 2 is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus in disassembled form and with empty ~ags.
Figure 3 is a vertical section of t~e apparatus taken along the verti-~S~
cal central axis and showing the apparatus in a partiall~ assembled form and having two bags fi~lled.
~ igure 4 -is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus being inserted into the centri-fuge bucket and locted at ti~e upper posltion in the bucket.
Figure 5 is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus at the lower position in the centri-Euge bucket.
Figure 6 is a vertical section of the centrifuge bucket containing ~n inserted bag taken along the vertical central axis and sho~ing separation of PPP
and rc in the bag.
Figure 7 is a ~ertical section of the conical bag together with its satellite bag taken along the vertical central axis and showing both bags in the inverted position with the blood reinfusion line connected.
Figure 8 is an enlarged fragmentary vertical central section through the capillar~ inlet port and a ball valve at the bottom of the conical bag.
Figure 9 is a ~ertical section of another version of the scaled-up platelets separation device taken along the vertical central axis and showing means for regulating flow rate and for disconnecting collapsible bag.
2Q Figure 10 is a fragmentary cross-section through a modular insert in-corporating a needle valve for the regulation of flow rate and a connecting nipple, and taken along the lines 16 and 16 shown in Figure 9.
Pigure 11 is a fragmentary cross-section through a modular insert in-corporating a needle valve for regulating flow rate and the spring loaded valve activated b,y~centrifugal force.
The apparatus shown in Flgure 1 and Figure 2 through Figure 8 is de-si~gned as~ a disposab,le s~stem consisting of three collapsible bags which are _ g _ 5~ ~
completely sealecl and will allow one to maintain sterility during all -the steps of ~h0 operation. Thus, the system is designed -to comply with the FDA require-ments of safety for l~uman use. This system consists of a conical bag 1 function-ing as a separation cllamber which is held in a rigid support 2 split into two halves (Figure 2) and having conical cavity. Below the conical bag 1 there is a satellite bag 3 attached which is filled with the elution medium such as normal saline. The satellite bag 3 is connected to the conical bag 1 by means of a short capillary tube 4 (Figure 1 and 8) which is covered with a small ball 5 functioning as a ball valve. On a side of the satellite bag 3 there is a stopper arrangement 6 for the sterile infusion of medium into the bag 3. The rigid sup-port 2 is also holding a collection bag 7 positioned above the conical bag 1.
Both conical and collection bags have puncturing-type connector-arrangements 8 and 9 which allow aseptic connection and disconnection of these bags by means of a double-ended sterile needle connector lO. In order to hold the puncturing-type connector arrangement 8 in place there is an annular ri.ng clamp 15 incorporated into the design of the rigid support 2 so that ~hen the two halves are assembled the connector arrangement 8 is secured during subsequent operational steps. Both halves o~ the rigid support 2 are held together by an o-ring 11 which also func-tions as a snap ring fitting into the groove 12 on the inner wall of the centri-2Q fuge bucket 13 and holding the rigid support 2 in its upper position within the centrifuge bucket. The indented configuration 14 shown at the lower end of the rigid support 2 is provided to prevent pinching of the bag 3 when the support 2 slides down and squeezes the bag 3.
The operational steps used in the separation of platelets with this system are illustrated in a diagrammatic series which is represented in Figure 2 througll Figure 8. Figure 2 shows a vertical sectional view of the device in unassembled form. All three bags, 3, 1 and 7, are shown empty and collapsed with 10 _ 5'~1~
the upper collection bag 7 being disconnected. ~n Plgure 3 i.s shown priming of the conical bag l with sallne and PPP. The conical bag 1 is shown inserted in one-half of the rigid support 2. Figure 4 shows an assembled system positioned inside the centrlfugal bucket 13. The o-ring 11 which holds together both halves of the support 2 also holds the assembled support in the upper position of the centrifuge bucket where the o-ring 11 snaps into the groove 12 in the bucket 13.
This holding arrangement allows one to subject the device to slow speed centri-fugation, for instance at 500 rpm, for about one minute in order to clear the top of the chamber from blood cells. Thereafter the centrifugation speed is in-creased to about 2000 rpm at t~hich the o-ring 11 is snapped off the groove 12 and the support 2 begins to slide down against the satellite bag 3, which forces saline through the capillary tube 4 into the conical bag 1. This action displaces PRP from the blood sample into the upper collection bag 7 as is illustrated in Figure 5. Thereafter the collection bag 7 is disconnected, placed into a smaller bucket of another centrifuge ~FigLIre 6), and centrifuged at high speed in order to obtain PC and PPP. PPP is then mixed with the blood remaining in the conical bag 1 ~Figure 7~, and blood containing both saline and PPP is reinfused into the donor. Figure 8 shows an enlarged sectional view of the capillary connector and the ball valve between the satellite bag 3 and conical bag l.
Platelets collected by this procedure contain no WBCs and a very small number of RBCs. Functionally, platelets appear normal as based on their morphol-og~, abilit~ to aggregate, taXe up serotonin, and in their survival time in the ~lood circulation of animals. Their ability to secrete ATP during aggregation is on the average 32% higher than that of control platelets obtained by slow speed centrifugation, which suggests that they are even more functionally intact t~an the control platelets.
The apparatus shown in Figure 9 and lO is a version of a scaled-up system represented in Figure 1 but incorporating only one collapsible bag 3 con-taining saline and having a conical separation chamber 17 housed inside the cylindrical body 18 which can move under centrifugal force inside the centrifuge bucket 13 and exerts pressure against the collapsible bag 3. The PRP receiving chamber 19 is sealed with the o-ring 20 to the cylindrical body 18 above the separation cham~er 17. The device also has a needle valve 21 (Figure 10) for the regulation of flow rate incorporated inside a modular insert 22 and having a nipple for connecting the collapsible bag 3.
~lgure 11 is a modular insert representing a possible version of an arrangement for delaying liqwid flow during the start of centrifugation until maximal centrifugal force activates ~alve 23. It also incorporates needle valve 21 for controlling flow rate.
The invention further provides a triple bag adapted to be received in a cen-trifugal apparatus for separating platelet rich plasma from a blood sample comprising:
. ~. (a) a central portion having a generally conical shape with a centrifugal.ly outer end at the ver-tex oE -the cone and a cen-trifugal]y inner end at the opposite end thereof and adap-ted to Gontain the blood sample, (b) a collapsible injection por-tion adapted to contain a volume of saline less than the volume of the central portion of the bag and communicating wi-th the centrifugally ou-ter end of the central portion for injecting saline into the central portion as the injection portion collapses, and (c) an expandable collection portion communicating with -the centrifugally inner end of the central portion for collecting platelet rich plasma displaced from the central portion.
The separation of dissimilar solid particles, such as platelets and other blood cells, is effected by holding red and white blood cells with the aid of centrifugal force at a steady state equilibrium in the chamber, preferably of a conical shape, while displacing platelet rich plasma (PRP) with an equivalent volume of normal saline which is filtering through the suspension of blood cells in the direction generally against the centrifugal force. 'I'he liquid medium en-ters the conical chamber at its vertex which is oriented away from the center of rotation, thereby being at the centrifugal ou-ter end of the chamber, while PRP
exits the chamber through its base, which is the centrifugal inner end of the chamber. The liquid flow is generated by means of a piston pump in response to centrifugal force, the apparatus is preferably designed as an insert to be used in a centrifuge swin~ing bucket, and consists of a cylinder and a piston, the latter incorporating both the conical separation chamber at its lower end and the PRP receiving chamber at its upper end. 'l'here is a needle valve in the piston controlling the flow rate of the medium flowing from the cylinder through -the passageway leading to the conical chamber's centrifugal outer end. To prevent an im~nediate discharge of blood cells from the conical chamber by the flow of saline at the start of centrifugation, a control means is provided for holding movement of the piston lnto the cylinder until a maximum centrifugal force is applied. The control means may comprise an o-ring on the piston received iTI a groove in the wall o~ the cylinder. This provision allows one to clear blood cells from the centripetal end of the chamber ~y sedimenting cells at a low centrifugal speed applied for one minute after which centrifugal speed is raised to a required higher value at which the o-ring snaps from the groove and the piston begins to force medium from the cylinder into the conical chamber.
Disclosed herein is a self-contained s~stem, as described above, for the efective collection of PRP from whole blood, prefe~ably from the same donor, lQ free of other blood cells and in a quantity and quality compatible with the re-quirements practiced in blood banks and in hospitals. The totally sealed, dis-posable, low-cost system consist o three interconnected collapsible plastic bags, held together in a rigid support which is fitted into a centrifuge bucket.
~ore particularly, the system o~ three bags consists of the middle bag, prefer-abl~ conical in shape, filled with blood and functioning as a separation chamber;
the lower bag holding normal saline for displacement of PRP from the middle bag;
and the upper bag for receiving PRP displaced from the middle bag. ~lso~ the system ;s sterile and incorporates the means for aseptic handling during all the procedural steps.
2Q ~eferring now to the accompanying drawings:
Pigure 1 is a vertical section of the scaled-up version of the appara-tus taken along the vertical central axis and showing the apparatus consisting of - tnree cGllaps~ible bags inserted into the centrlfuge bucket.
Fi~gure 2 is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus in disassembled form and with empty ~ags.
Figure 3 is a vertical section of t~e apparatus taken along the verti-~S~
cal central axis and showing the apparatus in a partiall~ assembled form and having two bags fi~lled.
~ igure 4 -is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus being inserted into the centri-fuge bucket and locted at ti~e upper posltion in the bucket.
Figure 5 is a vertical section of the apparatus taken along the verti-cal central axis and showing the apparatus at the lower position in the centri-Euge bucket.
Figure 6 is a vertical section of the centrifuge bucket containing ~n inserted bag taken along the vertical central axis and sho~ing separation of PPP
and rc in the bag.
Figure 7 is a ~ertical section of the conical bag together with its satellite bag taken along the vertical central axis and showing both bags in the inverted position with the blood reinfusion line connected.
Figure 8 is an enlarged fragmentary vertical central section through the capillar~ inlet port and a ball valve at the bottom of the conical bag.
Figure 9 is a ~ertical section of another version of the scaled-up platelets separation device taken along the vertical central axis and showing means for regulating flow rate and for disconnecting collapsible bag.
2Q Figure 10 is a fragmentary cross-section through a modular insert in-corporating a needle valve for the regulation of flow rate and a connecting nipple, and taken along the lines 16 and 16 shown in Figure 9.
Pigure 11 is a fragmentary cross-section through a modular insert in-corporating a needle valve for regulating flow rate and the spring loaded valve activated b,y~centrifugal force.
The apparatus shown in Flgure 1 and Figure 2 through Figure 8 is de-si~gned as~ a disposab,le s~stem consisting of three collapsible bags which are _ g _ 5~ ~
completely sealecl and will allow one to maintain sterility during all -the steps of ~h0 operation. Thus, the system is designed -to comply with the FDA require-ments of safety for l~uman use. This system consists of a conical bag 1 function-ing as a separation cllamber which is held in a rigid support 2 split into two halves (Figure 2) and having conical cavity. Below the conical bag 1 there is a satellite bag 3 attached which is filled with the elution medium such as normal saline. The satellite bag 3 is connected to the conical bag 1 by means of a short capillary tube 4 (Figure 1 and 8) which is covered with a small ball 5 functioning as a ball valve. On a side of the satellite bag 3 there is a stopper arrangement 6 for the sterile infusion of medium into the bag 3. The rigid sup-port 2 is also holding a collection bag 7 positioned above the conical bag 1.
Both conical and collection bags have puncturing-type connector-arrangements 8 and 9 which allow aseptic connection and disconnection of these bags by means of a double-ended sterile needle connector lO. In order to hold the puncturing-type connector arrangement 8 in place there is an annular ri.ng clamp 15 incorporated into the design of the rigid support 2 so that ~hen the two halves are assembled the connector arrangement 8 is secured during subsequent operational steps. Both halves o~ the rigid support 2 are held together by an o-ring 11 which also func-tions as a snap ring fitting into the groove 12 on the inner wall of the centri-2Q fuge bucket 13 and holding the rigid support 2 in its upper position within the centrifuge bucket. The indented configuration 14 shown at the lower end of the rigid support 2 is provided to prevent pinching of the bag 3 when the support 2 slides down and squeezes the bag 3.
The operational steps used in the separation of platelets with this system are illustrated in a diagrammatic series which is represented in Figure 2 througll Figure 8. Figure 2 shows a vertical sectional view of the device in unassembled form. All three bags, 3, 1 and 7, are shown empty and collapsed with 10 _ 5'~1~
the upper collection bag 7 being disconnected. ~n Plgure 3 i.s shown priming of the conical bag l with sallne and PPP. The conical bag 1 is shown inserted in one-half of the rigid support 2. Figure 4 shows an assembled system positioned inside the centrlfugal bucket 13. The o-ring 11 which holds together both halves of the support 2 also holds the assembled support in the upper position of the centrifuge bucket where the o-ring 11 snaps into the groove 12 in the bucket 13.
This holding arrangement allows one to subject the device to slow speed centri-fugation, for instance at 500 rpm, for about one minute in order to clear the top of the chamber from blood cells. Thereafter the centrifugation speed is in-creased to about 2000 rpm at t~hich the o-ring 11 is snapped off the groove 12 and the support 2 begins to slide down against the satellite bag 3, which forces saline through the capillary tube 4 into the conical bag 1. This action displaces PRP from the blood sample into the upper collection bag 7 as is illustrated in Figure 5. Thereafter the collection bag 7 is disconnected, placed into a smaller bucket of another centrifuge ~FigLIre 6), and centrifuged at high speed in order to obtain PC and PPP. PPP is then mixed with the blood remaining in the conical bag 1 ~Figure 7~, and blood containing both saline and PPP is reinfused into the donor. Figure 8 shows an enlarged sectional view of the capillary connector and the ball valve between the satellite bag 3 and conical bag l.
Platelets collected by this procedure contain no WBCs and a very small number of RBCs. Functionally, platelets appear normal as based on their morphol-og~, abilit~ to aggregate, taXe up serotonin, and in their survival time in the ~lood circulation of animals. Their ability to secrete ATP during aggregation is on the average 32% higher than that of control platelets obtained by slow speed centrifugation, which suggests that they are even more functionally intact t~an the control platelets.
The apparatus shown in Figure 9 and lO is a version of a scaled-up system represented in Figure 1 but incorporating only one collapsible bag 3 con-taining saline and having a conical separation chamber 17 housed inside the cylindrical body 18 which can move under centrifugal force inside the centrifuge bucket 13 and exerts pressure against the collapsible bag 3. The PRP receiving chamber 19 is sealed with the o-ring 20 to the cylindrical body 18 above the separation cham~er 17. The device also has a needle valve 21 (Figure 10) for the regulation of flow rate incorporated inside a modular insert 22 and having a nipple for connecting the collapsible bag 3.
~lgure 11 is a modular insert representing a possible version of an arrangement for delaying liqwid flow during the start of centrifugation until maximal centrifugal force activates ~alve 23. It also incorporates needle valve 21 for controlling flow rate.
Claims (16)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Apparatus for separating solid particles such as platelets from a liquid sample such as blood comprising (a) a body adapted to be subjected to centrifugal force and containing a cavity to receive a volume of displacing liquid therein, (b) a piston mounted in the body for movement into the cavity in response to centrifugal force on the piston with the piston containing a centrifugal cham-ber having inner and outer ends and adapted to receive the sample from which par-ticles are to be separated, and injection passageway means for movement of dis-placing liquid from the cavity to the centrifugal outer end of the chamber in response to movement of the piston into the cavity.
(c) a discharge passageway at the centrifugally inner end of the chamber for discharging particle rich liquid in response to injection of displacing liquid into the chamber, and (d) means for preventing flow of displacing liquid from the cavity to the chamber before centrifugal stratification of blood cells in the chamber.
(c) a discharge passageway at the centrifugally inner end of the chamber for discharging particle rich liquid in response to injection of displacing liquid into the chamber, and (d) means for preventing flow of displacing liquid from the cavity to the chamber before centrifugal stratification of blood cells in the chamber.
2. The apparatus of Claim 1 wherein said means for preventing flow com-prises control means for preventing movement of the piston into the cavity until a minimum centrifugal force is applied to the piston.
3. The apparatus of Claim 2 in which said control means comprises an O-ring on the piston received in a groove in the wall of the cavity.
4. The apparatus of Claim 2 in which the control means comprises valve means activated by centrifugal force in said injection passageway means.
5. The apparatus of Claim 1 characterized further by the inclusion of the valve means in said injection passageway means for controlling the flow rate therein.
6. The apparatus of Claim 1 characterized further by the inclusion of a blood sample in said chamber and a volume of buffered saline in the cavity.
7. The apparatus of Claim 6 in which the body of saline has a volume between 0.2 and two times the volume of plasma in the blood sample.
8. The apparatus of Claim 1 further comprising a collapsible bag in the cavity surrounding the body of displacing liquid and communicating with the injection passageway means.
9. The apparatus of Claim 8 characterized further by the inclusion of a second bag containing blood sample in the chamber and communicating with the collapsible bag in the cavity, and a third bag communicating through the discharge passageway with the second bag for receipt of platelet rich plasma.
10. The method of separating platelets from a blood sample comprising:
(a) supporting the blood sample in a centrifugal chamber having inner and outer ends, (b) subjecting a chamber to an initial centrifugal force of at least a predetermined minimum to stratify red cells in the sample away from the inner end, and (c) subjecting the chamber to a second centrifugal force while (1) injecting into the outer end of the chamber from a cavity a displacing liquid having a volume of between 0.2 and two times the volume of plasma in the sample at a flow rate less than out 1.0 ml. per minute per ml. of the blood sample, and (2) displacing platelet rich plasma from the inner end of the chamber at substan-tially the same volume and rate, with the displacing liquid ejected from the cavity by the second centrifugal force on the blood sample.
(a) supporting the blood sample in a centrifugal chamber having inner and outer ends, (b) subjecting a chamber to an initial centrifugal force of at least a predetermined minimum to stratify red cells in the sample away from the inner end, and (c) subjecting the chamber to a second centrifugal force while (1) injecting into the outer end of the chamber from a cavity a displacing liquid having a volume of between 0.2 and two times the volume of plasma in the sample at a flow rate less than out 1.0 ml. per minute per ml. of the blood sample, and (2) displacing platelet rich plasma from the inner end of the chamber at substan-tially the same volume and rate, with the displacing liquid ejected from the cavity by the second centrifugal force on the blood sample.
11. The method of Claim 10 in which said chamber has a generally conical cross-section and said displacing liquid is buffered saline, and the chamber is subjected to a greater centrifugal force during the injection than during the stratifica-tion.
12. The method of Claim 10 in which said displacing liquid is injected at a volume approximately equal to volume of plasma in the sample and at a rate of about 0.35 ml. per minute per ml. of the sample.
13. The method of Claim 10 in which the step of injecting the displacing liquid into the chamber is performed by impounding the displacing liquid in a support cavity and propelling the blood sample containing chamber into the cavity under the influence of centrifugal force.
14. The method of Claim 10 in which a sufficient number of blood cells are present in the chamber in order to form a dense cell suspension which has characteristics of a fluidized bed of particles and acts as a depth filter allowing platelets to pass through freely while maintaining other blood cells in a steady state equilibrium in the chamber.
15. The method of Claim 11 wherein the blood sample and saline are initially contained within respective bags interconnected through a capillary passage, the said bag containing the blood sample being contained within said first chamber and said bag con-taining saline being contained within said second chamber and where-in there is a third bag interconnected with the bag containing blood which is to receive platelet enriched plasma displaced from said blood sample during the injection of saline, said third bag being disposed centrifugally outside the centrifugally inner end of the first said chamber.
16. A totally sealable triple-enclosure bag adapted to be used in the method of Claim 15 for hermetically containing the blood sample and saline comprising: a central enclosure portion having a generally conical shape with a first end at the vertex of the cone and a second end at the opposite end thereof and adapted to contain the blood sample, a collapsible injection enclosure por-tion adapted to contain a volume of saline less than the volume of the central portion of the bag and communicating with the first end of the central enclosure portion for injecting saline into the central portion of the bag as the injection enclosure portion collapses, and an expandable collection enclosure portion communi-cating with the second end of the central enclosure portion for collecting platelet rich plasma displaced from the central enclosure portion.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US146,461 | 1980-05-05 | ||
| US06/146,462 US4268393A (en) | 1980-05-05 | 1980-05-05 | Apparatus for centrifugal separation of platelet-rich plasma |
| US06/146,461 US4269718A (en) | 1980-05-05 | 1980-05-05 | Process and device for centrifugal separation of platelets |
| US146,462 | 1988-01-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1185218A true CA1185218A (en) | 1985-04-09 |
Family
ID=26843938
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000376843A Expired CA1185218A (en) | 1980-05-05 | 1981-05-05 | Centrifugal separation of platelet rich plasma |
Country Status (5)
| Country | Link |
|---|---|
| CA (1) | CA1185218A (en) |
| DE (1) | DE3117710A1 (en) |
| FR (1) | FR2481614A1 (en) |
| GB (1) | GB2075376B (en) |
| SE (1) | SE8102776L (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11413796B2 (en) | 2018-10-09 | 2022-08-16 | Sacmi Cooperativa Meccanici Imola Societa' Cooperativa | Apparatus and method for processing cups |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1311989B1 (en) | 1999-03-30 | 2002-03-22 | Giammaria Sitar | PROCEDURE FOR ISOLATING FETAL CELLS PRESENT IN THE PERIPHERAL BLOOD. |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3800947A (en) * | 1971-07-16 | 1974-04-02 | P Smith | Reagent tube and centrifugally operated solid-liquid separating device |
| US4057499A (en) * | 1973-03-09 | 1977-11-08 | Buono Frank S | Apparatus and method for separation of blood |
| US3960727A (en) * | 1974-08-09 | 1976-06-01 | Hochstrasser Harry T | Apparatus and method for isolating soluble blood components |
| US3986506A (en) * | 1974-09-03 | 1976-10-19 | Baxter Travenol Laboratories, Inc. | Apparatus for separation of cryoprecipitate from blood plasma and method |
| US4007871A (en) * | 1975-11-13 | 1977-02-15 | International Business Machines Corporation | Centrifuge fluid container |
-
1981
- 1981-05-04 SE SE8102776A patent/SE8102776L/en not_active Application Discontinuation
- 1981-05-04 FR FR8108789A patent/FR2481614A1/en active Granted
- 1981-05-05 GB GB8113722A patent/GB2075376B/en not_active Expired
- 1981-05-05 CA CA000376843A patent/CA1185218A/en not_active Expired
- 1981-05-05 DE DE19813117710 patent/DE3117710A1/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11413796B2 (en) | 2018-10-09 | 2022-08-16 | Sacmi Cooperativa Meccanici Imola Societa' Cooperativa | Apparatus and method for processing cups |
| US11679534B2 (en) | 2018-10-09 | 2023-06-20 | Sacmi Cooperativa Meccanici Imola Societa' Cooperativa | Apparatus and method for processing cups |
Also Published As
| Publication number | Publication date |
|---|---|
| SE8102776L (en) | 1981-11-06 |
| GB2075376A (en) | 1981-11-18 |
| GB2075376B (en) | 1983-09-21 |
| DE3117710A1 (en) | 1982-04-08 |
| FR2481614B1 (en) | 1985-03-29 |
| FR2481614A1 (en) | 1981-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4269718A (en) | Process and device for centrifugal separation of platelets | |
| US4268393A (en) | Apparatus for centrifugal separation of platelet-rich plasma | |
| AU2003265160B2 (en) | Method and apparatus for isolating platelets from blood | |
| US6905612B2 (en) | Plasma concentrate apparatus and method | |
| US4911833A (en) | Closed hemapheresis system and method | |
| EP2080531B1 (en) | Apparatus and method for separating a volume of whole blood into at least three components | |
| US8226537B2 (en) | Blood processing apparatus with cell separation chamber with baffles | |
| US9737898B2 (en) | System for blood separation with gravity valve for controlling a side-tapped separation chamber | |
| CA1299551C (en) | Particle separation process | |
| JPH09276396A (en) | Centrifugal separator bowl for hematocrit | |
| WO1994006535A1 (en) | Apparatus and method for fractionating a liquid mixture | |
| JP2022520710A (en) | Devices and methods for concentrating platelet-rich plasma | |
| CA1185218A (en) | Centrifugal separation of platelet rich plasma | |
| EP0070159B1 (en) | Centrifuging apparatus and methods for separating fluids into components thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |