Plasma Freezer

Abstract

A plasma freezer for use in cryoprecipitation of antihemophilic factor from whole blood. Freezing and thawing tanks may be filled with novel cassettes containing plasma filled bags, while the associated red blood cells which have been separated by centrifuging are held at a uniform temperature to prevent deterioration.

Description

This invention relates to a novel plasma freezer and, more specifically, is directed to a plasma freezer particularly adapted for the use in the production of antihemophilic factor.

In recent years, it has been discovered that the antihemophilic factor separates from blood plasma through cryoprecipitation. The antihemophilic factor is important to control hemophilia, which is commonly known as the "bleeder's disease." Before the recent discovery, persons afflicted with this disease were given liberal transfusions of plasma, which is the clear liquid portion of the blood which contains the clotting or antihemophilic factor. Besides being expensive, the patient received other factors in the plasma when they were not needed. In actual practice, the antihemophilic factor (AHF) is all that is required for arresting or controlling bleeding in hemophiliacs. Accordingly, it is desirable to retain the plasma and red cells in a usable condition while separating the AHF from the whole blood, thereby permitting the remaining whole blood to be used for other purposes.

It has been found that AHF can be isolated by first centrifuging the whole blood to pack the red cells in the lower portion of the container. Then, the clear plasma above the red cells is then expressed into a satellite bag through a connecting tube which is isolated from the atmosphere. By a freezing and thawing process, the AHF is precipitated out of the plasma. The plasma may then be recombined with the red cells to form whole blood which has had the antihemophilic factor removed. It is essential that the freezing and thawing be accomplished under carefully controlled circumstances in order to assure that the quality of the remaining whole blood will not be affected. It is also important to maintain the freezing and thawing conditions uniform to assure the maximum concentration of AHF by the process without permitting deterioration of the plasma. In the prior art, this was attempted to be accomplished through a rather crude technique using a freezer section of a conventional refrigerator, and the results left something to be desired because of the lack of control over the process.

The present invention relates to a novel plasma freezer having a unique arrangement of freezing, thawing and holding tanks. Into these tanks are placed cassettes which act as carriers to protect plastic bags in which the red blood cells and plasma are stored. Through the novel arrangement, the plasma, even though separated from the red blood cells, is maintained sterilely connected to the container or bag containing the red blood cells. This bag may be carried in a cassette or may be stored in a holding tank which assures that the cells will be maintained at a uniform temperature to retain their quality throughout the freezing and thawing of the plasma. The novel design permits technicians and persons of a similar level of skill to cryoprecipitate out the AHF under controlled circumstances.

The novel freezer assures that uniformity in temperatures during the entire process will be maintained. Moreover, the use of the cassettes assures good thermal conductivity for expedient freezing and thawing while precluding contact between the plasma and red blood cell containers with the freezing and thawing baths. This assures maximum sterility and reduces the chance of damage to the bags. The production of AHF is maximized in a minimum amount of time. Other advantages will become apparent upon reference to the objects achieved.

It is an object of this invention to provide a novel plasma freezer particularly adapted for use in the production of antihemophilic factor.

It is a further object of this invention to provide a novel plasma freezer having three separate tanks for freezing, thawing and holding during the production of antihemophilic factor from blood plasma.

It is a further object of this invention to provide a plasma freezer which permits the extraction of antihemophilic factor from blood plasma by cryoprecipitation and permits recombination of the plasma and red blood cells while assuring retention of the quality of the plasma and red blood cells, making them suitable for further use as whole blood.

It is a still further object of this invention to provide a new and improved cassette particularly adapted for freezing, thawing and holding bags containing red blood cells and plasma.

Objects other than those specifically set forth will become apparent to those skilled in the art upon consideration of the accompanying drawings and following description.

In the drawings:

FIG. 1 is a perspective view of the plasma freezer of the present invention;

FIG. 2 is a longitudinal cross section taken generally along the line 2-2 of FIG. 1 and illustrating the thawing bath with cassettes positioned therein being shown in full elevation;

FIG. 3 is a transverse fragmentary cross section taken generally along the line 3-3 of FIG. 1 and illustrating the thawing, freezing and holding tanks in cross section;

FIG. 4 is a perspective view of a cassette with a blood container disposed therein;

FIG. 5 is an enlarged cross-sectional view taken generally along the line 5-5 of FIG. 4 and illustrating the bag and cassette in cross section;

FIG. 6 is a top plan view of the plasma freezer shown in FIG. 1;

FIG. 7 is a fragmentary free body view of the thawing tank;

FIG. 8 is a top plan view of the thawing tank shown in FIG. 7;

FIG. 9 is a side elevational view of the freezing tank with portions broken away to show the cooling coils;

FIG. 10 is a free body side elevational view of the holding tank;

FIG. 11 is a top plan view of the holding tank shown in FIG. 10;

FIG. 12 is a fragmentary perspective view of a typical thawing or freezing tank assembly;

FIG. 13 is a cross-sectional view taken along the line 13-13 of FIG. 12; and

FIG. 14 is an enlarged elevational view of the pump housing with the top of the tube broken away.

Referring now to FIG. 1, the plasma freezer of the present invention is indicated generally be reference numeral 10 and includes a cabinet 11 which may be mounted on casters 12 for ease of mobility, having a front face 14 which contains a control panel 15. The top of the plasma freezer 16 is provided with a motor housing 13 and three tanks or wells indicated generally at 17, 18 and 19, respectively. The tank 17 is a holding tank, while the tank 18 is a freezing tank, with the tank 19 serving as a thawing bath. Each of the latter tanks utilizes a liquid bath to effect good heat transfer. The circulating systems of these are the same and will be described in detail with reference to FIGS. 12--14. The plasma freezer unit shown is provided with transfer packs of whole blood indicated generally at 20 with the bags in the thawing tank being stored in cassettes 21 which will be described in greater detail with reference to FIGS. 4 and 5.

A brief summary of the method of cryoprecipitation may be beneficial to a more complete understanding of the present invention. The transfer packs 20 are of conventional design and may be purchased on the open market, and include a whole blood bag 22 and plasma bag 24 joined by a connecting tube 23.

Whole blood is taken directly from a blood donor through a tube (not shown) into the blood bag 22, having an anticoagulant of known type. The bag 22 is then centrifuged to collect the red blood cells at the bottom, leaving the clear plasma at the top. The clear liquid or plasma containing the antihemophilic factor is expressed through the connecting tube 23 into the satellite bag 24. The two bags 22 and 24 are maintained as a unit in airtight interconnected relation as shown in FIG. 1. The plasma bag 24 is taken through the freeze and thaw cycles to cryoprecipitate out the antihemophilic factor, while the red blood cells are stored in the bag 22 in the holding tank 17 at a uniform temperature to protect against deterioration. This process will be described in greater detail hereinafter.

In order to protect the plasma bags 22 against deterioration from immersion in the tank, they may be housed in the cassette 21. As seen in FIGS. 3--5, the cassette consists of a generally rectangular elongated container having a pair of laterally projecting flanges 25 and 26 at the upper extremity and side margins of the cassette 21. The interior of the cassette is coated with a suitable plastic coating 27 to prevent adherence of the transfer packs or blood bags 24 to the walls. The flange 26 may be provided with a handle 28 to facilitate handling of the cassette and bag 24 as a unit when switching it from the freezing bath to the thawing bath. The cassette provides an additional advantage in that it assures fairly uniform heat transfer from the liquid bath to the bag contents, thereby preventing any deterioration of the plasma and expediting the freeze and thaw cycles.

As seen FIG. 2, the thawing tank 19 is formed in a rectangular well of a depth sufficient to receive the cassettes 21 with a uniform clearance at their bottom wall as indicated at 30. The tank is filled between one-third and one-half with ordinary water. Depending upon the number of cassettes in the tank, the level will need adjustment. At the left-hand end of the thawing tank is provided a circulation system including a conduit 31 having flange portions 32 and 33 for attachment to the sidewall of the tank. The pump and circulating system, which will be described in detail with reference to FIGS. 12--14, recirculates the fluid continuously to maintain uniformity in temperature. As seen in FIG. 8, a third conduit 34 is joined to the tank at the same elevation as the conduit 33. A pair of coils 35 and 36 are wound in a race track pattern and joined to the bottom wall 37 of the tank by plates 39 through the action of nuts 49 which press the coils into intimate contact with the bottom wall of the tank 18. The coils are connected into the refrigeration system to permit refrigerant to be circulated therethrough. A strip-type heater 38 is fastened to the bottom of the tank 18 within the area bounded by the coils 35 and 36. Suitable sensing means of known type is provided to permit control of the heating or cooling of the thaw bath and thus maintain the temperature uniform. The desired temperature can be selected by adjustment of knobs on the control panel. Referring now to FIGS. 3 and 9, the freezing tank 18 is illustrated as being formed of a metal shell 40 into a boxlike configuration. A refrigeration coil is indicated generally at 41 and if formed by stamping recesses into a second sheet of metal which is subsequently welded or otherwise suitably attached fluidtightly to the outer wall 40. As seen in the lower right-hand corner of FIG. 9, the passages for the refrigerant are formed in a fashion to permit the coolant to directly contact the wall of the shell 40 to provide good heat transfer directly to the fluid contained in the tank. In this manner, the desired temperature of the tank may be maintained at the level selected even though cassettes at a different temperature are inserted.

In the preferred form of the invention, the freezing tank is filled between one-third and one-half full with either methanol, ethanol or an equivalent type of bath. A hose attachment 42 is provided to permit the level to be adjusted to compensate for changes in the number of cassettes contained in the freezing tank. The circulating system is similar to the thawing tank and will be described below with reference to FIGS. 12--14. The refrigeration coils are connected through suitable conduits 43 to a refrigeration system of known type (not shown) which is mounted in the base of the cabinet 11.

The circulation system for each of the freezing and thawing tanks is virtually identical and, therefore, in the interest of brevity, will be described with reference to the tank 80 in FIG. 12 which may be a freezing, thawing or similar type of tank. The tank 80 has a circulation assembly indicated generally at 81 and is adapted for fluidtight attachment to the end wall of the tank through the use of mounting flanges 83, 84 and 85. Obviously, any equivalent mounting arrangement may be used. The cycle of circulation is generally shown by the arrows wherein the liquid enters the system at the flange 83 and exits through the flanges 84 and 85 on opposite sides of the cassette for greater uniformity. The circulating system includes a pump housing 86 which is in the form of a T-fitting which is attached to a second T-fitting 87 forming the inlet to the pump housing. A stack 88 joins the upper end of the T-fitting 87 and forms a mounting for a motor indicated generally at 90. The motor 90 is located in the motor housing 13 well above the maximum level of liquid in the tank for safety. The pump housing 86 has opposite ends connected to elbows 91 and 92 which, in turn, are connected through the flanges 84 and 85, respectively, to elongated tubes 93 and 94 which are perforated along the sidewalls as at 97 and 98 are closed off at the ends. If desired, a spaces 95 may be used to maintain the tubes transversely spaced.

Referring now to FIGS. 13 and 14, the pumping arrangement will be described. The tube 88 has the motor 90 mounted at its upper end through a collar 100. A pump drive shaft 101 is coupled through a coupling 102 to the motor and extends through a guide bracket 103 into a plastic bearing 104 mounted in a housing 105 formed on the T-fitting forming the impeller chamber 86. A pair of collars 106 and 107 serve to prevent axial movement of the shaft relative to the guide 103.

At the lower end of the pump shaft 101 is provided an impeller 108 which functions to recirculate the fluid through the outlets 111 and 112 which are connected to the distribution tubes 93 and 94, respectively. In practice, the water or other liquid in the tank 80 enters the inlet 113 formed by the T-fitting 87 and is pumped out through the openings 111 and 112 for distribution through the perforations 97 and 98. The simplified form of pumping system eliminates the need for any special seals. Due to its unique design, it may be readily fabricated from parts available on the open market. It is acceptable for use with both the freeze and thaw baths and keeps the liquid bath continuously circulated for optimum uniformity in temperature, thereby guarding against cell deterioration.

Referring now to FIGS. 3, 10 and 11, it can be seen that the holding tank 17 is of greater depth than either of the freezing or thawing tanks. As shown in FIG. 3, the plastic bag containing the red blood cells is stored in the holding tank 17 without a cassette needed because no liquid medium is used. The holding tank 17 consists of a metal shell 50 formed to a boxlike configuration and having a series of cooling coils 51 wound adjacent the top. Suitable means such as the clamps 52 and 53 hold pg,13 the coils in good heat transferring relation with the wall 50. The coils 51 are connected to the refrigeration source through a control which is responsive to changes in temperature. Through adjustment of the controls on the control panel 15, the holding tank and thawing tank are normally set to 4.degree. C. (+39.2.degree. F.). The refrigeration unit which is contained in the cabinet 11 and the strip heater on the bottom of the thawing tank 19 will energize and operate in response to sensors of conventional type to maintain the temperature at the level selected.

In operation, the freezing bath and thawing bath are filled with methanol and water, respectively. As pointed out above, a drain hose attachment on each of these tanks permits part of the liquid to be drained off so that the level may be adjusted to compensate for insertion and removal of cassettes. The unit is connected to a source of electrical power and the switches 60 and 61 on the control panel 15 are energized to turn the unit on and energize the circuit for the strip heater 38 in the thawing tank. The desired thawing bath temperature, usually 4.degree. C., may be selected through adjustment of control knob 62. The temperature level of the holding tank may be adjusted through the knob 63. Each of these knobs is provided with an associated indicating means 64 and 65, respectively, which permits visual reading of the existing temperature in each of these tanks. The desired temperature of the freezing bath within the limits of the refrigeration unit may be selected by means of control knob 66 with indicator 67 set to any desired temperature. The whole blood in the bag 22 is centrifuged to pack the red blood cells in the lower part of the bag. The clear liquid or plasma above the red cells is expressed through the connecting tube 23 into the satellite bag 24.

The satellite bag 24 containing the plasma is then placed in the cassette 21 and a sharp rap delivered to the bottom of the cassette. This serves to shape the bag and contents to conform to the interior shape of the cassette 21 for uniform and better heat transfer. The red blood cells remain attached through the tube 23 and are placed in the holding tank 17. The cassette 21 containing the plasma is placed in the freezing bath in the freezing tank 18 where freezing is completed in approximately 15 to 30 minutes.

The cassette 21 is then transferred into the thawing bath which is preferably maintained at 4.degree. C. Any drop in temperature of the thawing bath will be compensated for automatically by the strip heater becoming energized. Should the bath become too warm, refrigerant will be circulated through the coils 35 and 36 to bring the temperature to the level selected. Circulation of the liquid in the freezing and thawing baths is achieved by the circulation system 81 to maintain temperature uniformity. The frozen plasma will then thaw in about 2 hours at 4.degree. C. or less time if the temperature is raised. The white stringy substance remaining in the satellite bag after thawing is the antihemophilic factor. The clear liquid remaining is plasma which may be expressed back through the tube 23 into the bag 22 containing the red blood cells to form whole blood which may be used or dried as desired. The antihemophilic factor remaining in the plasma bag is collected for use in combating hemophilia.

From the foregoing, it can be seen that a simple plasma freezer arrangement is presented by the present invention. The use of cassettes facilitates rapid and easy handling of the bags containing the plasma. The use of the novel cassettes shields each of the plasma bags from direct contact with the solution in the freezing and thawing baths. The cassettes provide maximum conductivity and enchance the freezing and thawing processes. The coating in the cassettes facilitates ease in removal of the bag when the freeze and thaw process has been completed.

Upon a consideration of the foregoing, it will become obvious to those skilled in the art that various modifications may be made without departing from the invention embodied herein. Therefore, only such limitations should be imposed as are indicated by the spirit and scope of the appended claims.

Claims

We claim:

1. A plasma freezer for use in maintaining interconnected containers of plasma and red blood cells at desired temperatures for freezing, storage and thawing, respectively, said plasma freezer including a receptacle for reception of said containers carrying plasma, means to maintain said receptacle at a temperature below freezing and thereby freeze said plasma, a second receptacle located adjacent the first receptacle and adapted to receive containers of red blood cells, means to maintain said second receptacle at a selected temperature slightly above freezing, a third receptacle adjacent said second receptacle, and means to maintain said third receptacle at a temperature slightly above freezing to cryoprecipitate antihemophilic factor from said plasma.

2. The plasma freezer of claim 1 including means to continuously circulate diverse liquid baths in said first and third receptacles to provide for uniform freezing and thawing.

3. A plasma freezer for use in cryoprecipitating antihemophilic factor from whole blood while maintaining other factors of said whole blood in a condition suitable for recombination and use as whole blood, said plasma freezer comprising a cabinet housing first, second and third tanks, each of said tanks being isolated from the others, means to maintain one of said tanks at a temperature well below freezing, heater means in a second of said tanks to maintain said tank at a selected temperature slightly above freezing and a third tank having means to maintain said tank at a temperature of about 4.degree. C. to prevent deterioration of red blood cells during the cryoprecipitation process.

4. The plasma freezer as defined in claim 3 wherein said first tank contains a liquid bath of ethanol.

5. The plasma freezer as defined in claim 3 wherein each of said freezing and thawing tanks is filled with liquid and includes means to continuously circulate said liquid.

6. The plasma freezer of claim 3 wherein a plurality of cassettes are positioned in each of said tanks, said cassettes containing plastic bags substantially filling said cassette to provide for uniformity in heating and cooling.

7. The plasma freezer of claim 3 wherein said second well is partially filled with a liquid and includes means to maintain said second tank at a temperature slightly above thawing.

8. A plasma freezer particularly adapted for cryoprecipitation of antihemophilic factor from plasma while maintaining the red blood cells separated from said plasma and in a condition where recombination can take place without exposing said red blood cells and said plasma to atmosphere and while storing said red blood cells at a temperature to preserve the same, said plasma freezer including a cassette adapted to contain a plastic bag having plasma therein, a second bag containing said red blood cells and being joined through a tube to said bag containing said plasma, a freezing tank having means associated therewith to maintain said tank at a temperature below freezing, said freezing tank being adapted to receive said cassette with a cassette containing said plasma bag for freezing thereof, a thawing tank located adjacent said freezing tank and having means associated therewith to maintain said thawing tank at a selected temperature above freezing, said thawing tank being adapted to receive said cassette in uniformly spaced relation relative thereto, and a holding tank for receiving said bag containing said red blood cells, said holding tank having means associated therewith to maintain said red blood cells at a uniform temperature to prevent deterioration thereof.

9. The plasma freezer of claim 8 wherein each of said cassettes is coated with a low-friction coating to prevent adherence of the bags thereto.

10. The plasma freezer of claim 8 wherein each of said freezing and thawing tanks is filled with a liquid bath and includes means to continuously circulate said liquid bath for uniformity in temperature. 11In a blood freezing arrangement wherein blood is stored in plastic bags for freezing and thawing to cryoprecipitate antihemophilic factor, the improvement comprising a cassette for use in handling said bags containing plasma, said cassette being formed of a material having good heat transfer characteristics to minimize freezing and thawing time, and further being coated along the interior walls with a plastic coating to eliminate

adhesion of said plastic bag to said cassette. 12. The improvement of claim 11 wherein the exterior of said cassette is coated with a black substance for greater heat absorption and uniform distribution.