CA1038313A - Plasma collection system and bottle therefor - Google Patents

Abstract

PLASMA COLLECTION SYSTEM
AND BOTTLE THEREFOR

Dennis F. Shine & Gunther W. Torau Abstract of the Disclosure There is disclosed herein a method for collecting blood plasma in plastic bottles wherein the blood plasma can be stored for periods of time and can then be utilized in obtaining blood fractions therefrom.
The method includes the concept of filling a previously sterilized and hermetically sealed bottle with blood plasma. The bottle, after filling, is sealed at the neck portion thereof by means of heat sealing. The portion of the bottle above the heat seal is severed. Thereafter, the filled bottle is frozen and transported to the site for use. The bottle containing the plasma is then thawed and conveyed to a plasma removing device. The plasma is removed by severing a portion of the bottom of the plastic bottle, thereby permitting the liquefied plasma to flow therefrom into a collection vat. The bottle in which the plasma is collected and stored has a unique configuration in that it is a blow-molded bottle having a cap thereon which is produced integrally with the bottle so that it is always in a sterile condition. In one embodiment, the cap is broken from the top of the bottle, thereby exposing a mouth having a threaded config-uration thereabout so that a cap may be screwed thereon. The cap has means for venting and for introduction of a probe through which the plasma is conveyed into the bottle. In another embodiment, the top of the bottle terminates in a membrane suitable for piercing with a probe and a venting arrangement is included, whereby the plasma can be charged into the plastic bottle. Below the mouth, there is a flattened neck portion providing an area at which a heat sealing means can be applied to further compress into abutment the neck and to heat seal same in that condition. The upper portion of the mouth carrying member can be severed from the bottle.

Description

Background of the Invention Much progress has been made in the handling of plasma and whole blood obtained from human donors. Especially, considerable activity has been generated with respect to the collection of plasma which has a con.siderably longer shelf life than whole blood. Whole blood is collected by conventional means well known in the art. ~he plasma is removed from the whole blood by centrifugation, again, employing con-ventional devices. As an aside, new concepts include the removal of the cells from plasma through centrifugation and the reintroduction of the cells to the donor, thereby permitting the donor to recoup a good portion of that which has been donated. In that way the donor may give blood on more occasions than would heretofore be possible.
~he need for the reintroduction of the blood cells to the donor has become extremely important in view of the paucity of blood that is available, Secondly, there has been a considerable increase in the need for plasma in view of the beneficial fractions that may be obtained there-from through various sophisticated processes. Blood plasma is collected at many areas throughout the world for use in central laboratories that may be located quite remote from the site of collection. Consequently, the plasma, having an already long shelf life, is further enhanced in being able to be frozen. ~he plasma is shipped in the frozen state to the labor-atory at which the plasma is thawed and fractionated by well known methods ~38313 such as described, for example, in U. S. Patents 3, 560, 475; 3, 631, 018;
3, 682, 881; and 3, 763, 135.
In order to provide sterility at the collection point and to retain the plasma in separated noncommingled condition, it is desirable to collect the plasma in separate bottles containing approximately one quart of plasma and to freeze the plasma in such bottles until they are thawed. ~he bottles are then opened and the plasma is dumpèd into a single collection vat.
Ordinary use of bottles provides unsterile conditions at the site of collection.In many instances, blood is collected in an open system in which the liklihood of bacterial contamination exists throughout the bottle and it therefore is necessary to autoclave or gas sterilize the entire bottle and its contents.
In other cases, the bottles merely have a c ap which has been screwed on to the mouth of the bottle and the bottles then must be opened prior to filling.
It has been found on occasion that bacteria may be harbored on the thread of the bottle or under the underside of the cap. In order to avoid such contam-ination, the mouth of the bottle must be sterilized prior to use.
Ihe U. S. government has promulgated regulations that require plasma collection bottles to be in a sterile condition, even though the plasma subse-quently will be treated in a manner that will certainly insure sterility.
Accordingly, the plasma collection bottle included in the present concept is blow-molded with an integrally formed cap under sterilizing conditions.

Summary of the Invention ~he present invention provides an ingenious plasma collection system and a bottle for use in connection therewith. ~he bottle is manufactured by blow-molding techniques from thermoplastic resins suitable for blow-molding such as the polyolefin resins, for example, polyethylene or polypropylene, ~(~38313 and other materials which are compatible with plasma. U. S.
Patents 3,597,793; 3,730,372; and Re. 27,155; and British Patent No. 1,318,030 illustrate blow-molding apparatus which can be adapted for blow-molding and heat sealing the bottle. The bottle has an essentially cylindrical configuration wit,h a neck portion that is not cylindrical but' has been flattened to a considerable degree. Above the neck is what can be termed a mouth portion which ln one embodiment has a pierceable membrane. In another embodiment the mouth portion has a threaded area and a breakaway cap po3itioned thereon.
In both embodiments, the thermoplastic bottle is sterile blow-molded and hermetically sealed in a single operation whereby there is no contamination of the inside of the bottle due to the conditions employed turing the blow-molding and heat sealing of the bottle. These conditions include the high temperature of the resin during molding; steam ~terilization of the blow lines; use of " filtered air or sterilizing gas during blow-molding; and provision ...
of a bottle configuration adapted to heat sealing after filling with plasma. The bottle 80 formed can then be transported to the situs of a blood collection room anywhere in the world. In one em-bodiment the cap is broken away from the mouth and a second cap is attached thereto which has been previously packaged and maintained in a sterile condition. The new cap p'ossesses an area for venting containing a plug of a fibrous filter material and an area through which a plastic spike or a sharpened hypodermlc-like needle can be plunged wherein the proximal end has a flexible conduit attached thereto which has been previously attached to a source of plasma.
The plasma is pumped from the source into the thermoplastic bottle.
Thereafter, the bottle is subjected at the flattened neck portion thereof to compression and heating, whereby the flat portion is further compressed into ~lh / ~

touchlng relatlonshlp, The part above the hest sesled ~rea containing the puncture sp~ke or needle then can be severed as desired. The plasma filled bottle is subsequently frozen, after whlch lt can be transported to the place for further collection. The plasma ln the bottle is then thawet prlor to emptylng the contents therefrom.
For ease of removal of the contents, the filled bottles are positioned on a conveyor so that they can be transported to a position where a cutting tevice severs a portion of the bottom of the bottle thereby permitting the liquefied plasms to flow therefrom unter the aegis of gravity into a central collection vessel.
Thus, in brosd terms this aspect of the invention maybe tescribet as a thermoplastic blow-moltet bottle containing a msmmalian liquid comprising a cylintrical main body, a bottom, sait main boty at the entire top thereof converging upwardly ant inwartly terminating in a completely flattenet portion whereby a portlon of the inner surfaces are atheringly engaged to one another along an area perpendicular with respect to the longitutinal axis of sait bottle.
Another aspect of this invention maybe broadly describet as a method for collecting, storing and utilizing a liquit obtained from a mammalian donor comprising providing a tubular means having two open ends, connecting one end of the tubular means with an opening through the top of a thermoplastic bottle, which has been sterile blow-molded and hermetically sealed without a port and with a flattened constrictet neck portion, connecting the other end to a source of the mammalian liquid, introducing a quantity of the mammalian liquit from the source through the tubular means into the bottle, further flattenlng the constricted neck portlon whereby the inner surfaces of the opposltely dlsposed flattened constrlcted neck portion sealingly abut, slmultaneously applying heat to the ~4 .
1_ 5~(~ 5 -flattened neck portlon whereby the abuttlng surfaces adhere to one another, then freezlng the mammallan liquid ln the bottle, and storlng the frozen mammalian llquld.
Brief DescrlPtlon of the Drawlngs Flgure l 18 a perspective vlew of one embodlment of the thermoplastic blow-molded bottle of the present lnventlon.
Flgure 2 i8 one slte vlew of the bottle of Figure 1.
Flgure 3 is another slde vlew of the bottle of Flgure 1, Figure 4 is a top view of the bottle of Flgure l.
Flgure 5 ls a bottom vlew of the bottle of Flgure 1.
Flgure 6 is a perspective fragmentary view of another embodiment of the bottle of the present invention.
Figure 7 is a perspective view illustrating the removal of the cap from the embodiment shown in Figure 6.
Figure 8 is a perspective view of a screw-on cap having a suitable vent and two capped ports therein.

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Figure 9 is a perspective view of the bottle of the present invention having a screw cap thereon and a conduit having at one end a plastic spike thrusted therethrough and wherein the conduit at the other end is secured to a source of plasma, said source being in a press for expressing the plasma therefrom.
Figure 10 is a cross-sectional view of the neck portion of the bottle of the present invention, Figure 11 is the same view as in Figure 10 wherein means is included to compress and heat seal said neck portion.
Figure 12 is a similar view as Figures 10 and 11 but wherein a cutting device is employed to sever the bottle through said heat sealed and compressed neck portion.
Figure 13 is a perspective view after the severing step, Figure 14 is a perspective view of a conveyor system and one embodi-ment of a cutting means for severing through the bottom portion of the thermo-plastic bottle and a collection vessel in association therewith, Figure 15 is a cross-sectional view taken along line 15-15 of Figure 14.
Figure 17 is a perspective view of the use of the bottle shown in Figure 1 wherein the plastic spike is seen to be plunged into the pierceable membrane and the spike has attached at the other end thereof a flexible conduit.
Figure 18 is a flow diagram showing the steps of the method of the present invention, Figure l9 is a perspective view of a bottle holding means and a thermo-plastic bottle held in an upside down position.

Figure 20 is a perspective view of another embodiment of a cutting means for severing through the bottom of the thermoplastic bottle held in the bottle holder of Figure 19.
Figure 21 is a perspective view of the severed bottle being inverted .~ to dump plasma into a collection vessel.
Figure 22 is a perspective view of the severed bottle of Figure 21 held inverted until all the plasma has been dumped.

DE~AILED DESCRIPl~ION OF ~HE INVEN~ION

~he present invention relates to an ingenious method for collecting plasma and, especially, the bottle which is to be used to store the plasma during the transportation thereof from the collection site to the laboratory for utilization. With regard thereto, attention is directed to Figures 1-5 for further understanding the bottle of the present invention.
~he bottle is shown generally by reference numeral 11. ~he bottle 11 has a body 12 having a cylindrical configuration. The bottle has a con-verging shoulder portion 13 at the upper end thereof. ~he shoulder portion is flattened at neck 14 to produce a constriction area of a flattened config-uration. l he portion above the flattened area widens and terminates in a cylindrical upper portion 15 to which a widened portion 16 is integral. ~he top of the bottle terminates in a pierceable membrane 17. ~he bottom 19 of the bottle has depending semi-annular members 18 which is somewhat dictated for construction purposes in order to obtain strength as a result of the type of mold being used.
From Figures 6 and 7, it will be appreciated that the bottle in this embodiment of the present invention has a somewhat different configuration than the embodiment of Figures 1 to 5 above the flattened neck portion 14 where it has become wider again, Instead of having the cylindrical portion 15, the embodiment of Figures 6 and 7 possesses a cylindrical portion 21 having screw threads 22 thereon. Again, a widened portion is included as identified by reference numeral 23. This portion constitutes a cap which can be broken away as is seen from Figure 7 to reveal an open mouth 24.
Inasmuch as this embodiment has screw threads 22, it will be seen that a screw cap can be affixed thereto after said cap is broken away. Accord-ingly, attention is now directed to Figure 8 which illustrates a screw cap 26 having a top 27 and a depending skirt 28 having a plurality of knurls thereonto facilitate gripping thereof. Not shown are the screw threads for mating with the screw threads 22 on the bottle of the embodiment shown in Figures 6 and 7. ~he screw threads are located internally with respect to skirt 28 At the top of the cap 26 ther0 is a short tubular extension 29 which is open at one end but is capped with a plastic or a rubber cap~, After removal of cap 30, a plastic spike or metal needle can be plunged through tubular extension 29, Additionally, a vent 31 is positioned at the top 27 so that air can be expelled from the bottle as the bottle is filled through cap 30.
In order to illustrate the filling technique to be utilized in conjunction with the present invention, plasma is collected or charged into a flexible thermoplastic bag 40 which is mounted between a fixed upright wall 41 and a hinged second wall 42 of a plasma extractor 48. ~he hinged wall 42 is hinged at 43 and has a lever 44 so that between the fixed wall and the hinged wall the thermoplastic bag 40 containing the plasma is squeezed therebetween. ~he plasma is flowed through flexible conduit 45 in the direction of the thermoplastic bottle 11. Prior to the squeezing, cap 30 is removed and a plastic spike 46 is plunged through tubular extension 29. ~he spike can also be a metal needle of the hypodermic type so that it is sharpened with a bevel at one end in a ~03W13 conventional manner and the other end is affixed to the conduit 45. A radially extending flange 47is utili~ed to facilitate gripping. When the conduit has been suitably connected to the bottle 11 the lever 44 is pushed upwardly, thereby squeezing hinged wall 42 against the outer surface of thermoplastic bag S 40, and thus extracting out the plasma into the bottle 11. A second unit of plasma collected in a thermoplastic bag 40 can be similarly extracted and transferred to bottle 11 with another such transfer set with a spike plunged through the secondtubular extension 29.
After the bottle has been suitably filled, it is positioned in a manner so that the flattened neck portion 14 has one side thereof in abutment with heat sealing bars 50 and 51, one of which is shown as a fixed member 50 and the other as a movable member 51 at the other side thereof. ~he members 50 and 51 are suitably heated as by electric resistance means (not shown). ~he heated members soften the thermoplastic material of the flattened portion 14 of the neck so that as lateral pressure is applied to member 51 to move it in the direction shown by the arrow, that is, towards member 50, the flattened portion 14 of the neck will be further compressed and crushed. It can be readily seen from Figure 11, that the neck has been completely collapsed so that the internal~urfaces thereof are in abutment; and because they have been heated, they will now become heat sealed together.
~hereafter, the bottle is severed at flattened neck portion 14 such as by shearing or cutting. 'rhis is illustrated in Figure 12 wherein blade 53 of a cutting tool is positioned against one side of the collapsed and heat sealed neck and blade 54 of the cutting tool is at the other side thereof. By closing the blades of the cutting tool, the upper portion of the bottle is severed from the remaining main body as can be seen from Figure 13 which is a perspective view showing the fact that the top of the bottle has been severed.

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After the top has been severed as indicated heretofo~e, the th~rmo-plastic bottle containing the plasma is subjected to a quick freezing step so that the plasma therein is frozen. By employing a thermoplastic bottle, the plasma does not cause an untoward expansion such as would burst a conven-tional glass bottle. Moreover, the bottle is preferably only partially filled, such as about one-half filled, to allow for plasma expansion, ~he frozen plasma is then transported to the laboratory for utilization as desired at a time remote in time from the period of collection.
When it is desired to utilize the plasma and to remove the contents from the thermoplastic bottle, the plasma is permitted to become thawed by conven-tional methods and means. When it has became suitably thawed, it can be fed along with a number of other such thermoplastic bottles to a conveyor system which can be a belt conveyor system as illustrated by Figure 14. In the embodiment shown in Figure 14, the thermoplastic bottles containing plasma are moved in the direction of a cutting tool while the thermoplastic bottles A containing the plasma are in a slightly inclined position. ~he belJis shown by Figure 17 and the cutting tool is a circular device 61 which is powered by a suitable motor means 62. Hold down rods 63 are positioned so that the cutting tool 61 can penetrate the cylindrical portion of the bottle near the bottom thereof as is more fully understood from Figure 15.
Inasmuch as the cutting tool 61 desirably is extremely thin and sharp so that none of the thermoplastic material is severed therefrom as shavings, the slit under ordinary conditions will be very thin so that it is desirable to open up the cut to more efficaciously permit the removal of the plasma.
Accordingly, as the thermoplastic bottles are transported after the cutting stage, a cam surface 64 is provided which is designed to move the bottom portion that has been severed into a more horizontal condition while the hold ~038313 down means 63 maintain the bottle in the inclined position taken in conjunction with the moving belt 60. By opening up the bottle in the manner shown in Figure 16, the plasma 65 is permitted to drop out of the bottle into a collection vessel 66 from which the plasma is commingled with a plurality of plasma collected from many thermoplastic bottles of the same type with which the present invention is concerned.
Another embodiment for cutting the thermoplastic bottle and removing the contents is illustrated by Figures 19 to 22. In this embodiment, the bottle is held vertically upside down in fingers 73 of holder 74. ~he bottle is then fed through band saw 75 whereby the bottom (which appears at the top in the -upside down position) is cut off. ~he bottle is then carried to a position above a collection vessel and inverted in the direction of the arrow as shown in Figure 21, whereby the entire plasma contents are dumped into the collection vessel as shown in Figure 22.
As was stated in the above, another embodime~1t of the present invention concerns! a bottle of the thermoplastic type constructed in the same manner as above, Accordingly, attention is directed to Figure 17 to show the use of the bottle as a receptacle for plasma. Figure 17 shows a bottle having a config-uration of the type shown by Figures 1-5. ~he pierceable membrane 17 is seen to about to be plunged therethrough by means of a plastic spike 68 which can also be, as stated herein before, a metal hypodermic needle. ~he plastic spike 68 has an outwardly radiating flange of an annular configuration 69 so that it can be easily gripped. ~he proximal end of the spike has a conduit 70 attached thereto whose end terminates at a source of plasma such as shown in Figure 9. ~he arrow indicates the fact that the spike 68 is about to be plunged into the pierceable membrane 17. Additionally, the pierceable membrane already has been punctured with a short sterile tube 71 having a sterile fibrous ~3 plug 72 therein. l~he tube 71 acts as a venting means so that the air captured in the thermoplastic bottle can be vented to the atmosphere as the plasma is pumped therein.
In the foregoing, considerable attention has been directed to the embodiments of the thermoplastic bottle which include the concept of a method for collecting and storing plasma, With special reference to the method of the present invention as herein disclosed, attention is specifically called to Figure 18 for a diagrammatic flow diagram to show the manner in which the thermoplastic bottle is used in the collection of plasma. It will be seen that as an initial step after the thermoplastic bottle has been attached to a source of plasma, the thermoplastic bottle is filled with plasma. As a next step, the neck portion which has been previously flattened is sealed. l~he portion of the bottle above the heat sealed area is then severed by suitable means as has been heretofore discussed. 'rhereafter, the contents in the thermoplastic bottle are subjected to freezing temperatures in order to freeze the plasma. After freezing, the thermoplastic bottle containing the plasma can be transported in the frozen state or can be stored as desired. Prior to emptying of the thermo-plastic bottle, the plasma is stored in a suitable and conventional manner. As a further step in the method of carrying out the present invention, the bottom portion of the thermoplastic bottle can be cut in order to provide an opening from which the plasma can be obtained which is then collected in a suitable vessel from which the plasma can be removed for fractionating purposes as desired.
It will be appreciated that the present invention is not limited to the specific examples set forth above and that various other examples and modifications of the foregoing examples will be apparent to the person skilled in the art after reading the foregoing specification without departing from the - lZ --:1038313 spirit and scope of the invention. All such further examples and modifications thereof are included within the scope of the invention as defined in the appended claims.

Claims (22)

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

1. A method for collecting, storing and utilizing a liquid obtained from a mammalian donor comprising providing a tubular means having two open ends, connecting one end of said tubular means with an opening through the top of a thermoplastic bottle, which has been sterile blow-molded and hermetically sealed without a port and with a flattened constricted neck portion, connecting the other end to a source of said mammalian liquid, introducing a quantity of said mammalian liquid from said source through said tubular means into said bottle, further flattening said constricted neck portion whereby the inner surfaces of the oppositely disposed flattened constricted neck portion sealingly abut, simultaneously applying heat to said flattened neck portion whereby the said abutting surfaces adhere to one another, then freezing the mammalian liquid in said bottle, and storing said frozen mammalian liquid.

2. The method of claim 1 including the step after the said inner surfaces have been adhered together under the aegis of heat of severing that portion of the neck above the said surfaces that have been adhered together.

3. The method of claim 2 wherein the said bottle cutting step is accomplished by radially slicing open the bottle near substantially the bottom portion.

4. The method of claim 3 wherein the said bottom portion is pried apart from the bottle whereby the mammalian liquid may be more easily poured therefrom.

14 The method of claim 1 wherein said one end of said tubular means terminates in a sharpened cannula and wherein said end is connected to an opening in the top of said bottle by plunging said sharpened cannula through said top.

6. The method of claim 1 including the steps of breaking off the uppermost portion of the neck to provide an opening to the inside of the bottle, affixing a cap to said opening, and then obtaining egress through a port in said cap by means of a sharpened cannula attached to said tubular means which is plunged through said port.

7. The method of claim 5 including the step after the said inner surfaces have been adhered together under the aegis of heat of severing that portion of the neck above the said surfaces that have been adhered together.

8. The method of claim 6 including the step after the said inner surfaces have been adhered together under the aegis of heat of severing that portion of the neck above the said surfaces that have been adhered together.

9. The method of claim 7 wherein the said bottle cutting step is accomplished by radially slicing open the bottle near substantially the bottom portion.

10. The method of claim 8 wherein the said bottle cutting step is accomplished by radially slicing open the bottle near substantially the bottom portion.

11. The method of claim 1 wherein the mammalian liquid is blood plasma.

12. The method of claim 9 wherein the mammalian liquid is blood plasma.

13. The method of claim 10 wherein the mammalian liquid is blood plasma.

14. A thermoplastic sterile blow-molded and hermetically sealed bottle comprising a main body, a bottom, said main body at the top thereof converging upwardly and inwardly terminating in two confronting flattened portions providing a relatively constricted area, a wider portion above said constricted area, a cylindrical portion above said wider portion, and said cylindrical portion terminating in an integrally formed web means.

15. The bottle of claim 14 wherein the web means is a pierceable membrane.

16. The bottle of claim 14 wherein said cylindrical portion includes an upper larger diameter portion and said web means terminates the upper larger diameter portion.

17. The bottle of claim 16 wherein the web means is a pierceable membrane.

18. The bottle of claim 16 wherein a weakened breakaway line is included at the beginning of the upper larger diameter portion whereby the upper larger diameter may be broken off and means is provided in the remaining cylindrical portion to which a closure may be fastened.

19. The bottle of claim 14 wherein the main body is cylindrical.

20. The bottle of claim 15 wherein the cylindrical portion is concentric with said cylindrical main body.

21. A sealed thermoplastic blow-molded bottle containing mammalian blood comprising a cylindrical main body, a bottom, a top portion, the entire top portion from the main body converging upwardly and inwardly terminating directly in a completely flattened portion, said flattened portion having inner surfaces which are heat sealingly engaged to one another along an area perpendicular with respect to the longitudinal axis of said bottle for a length less than the diameter of said main cylindrical body directly thereunder and the top of the bottle terminates with an edge which is perpendicular to the longitudinal axis of said bottle.

22. The method of claim 1 including the additional steps of thawing the frozen mammalian liquid, thereafter cutting an opening in said bottle and pouring the mammalian liquid therefrom.