FIELD

The invention relates to a method of needless fluid transfer from specimen collection tubes into syringes. The invention and the method have applications in biological, pharmaceutical, and medical fields where extraction of fluids and separation of fluid fractions take place. A preparation of platelet rich plasma (PRP) and separation of platelet poor plasma (PPP) from whole blood are just some of many uses for the device that employ the method of transfer described herein.

BACKGROUND

Platelet Rich Plasma (PRP) is increasingly being used in various medical procedures as a catalyst for regeneration processes. PRP consists of blood plasma with concentrated platelets, which contain various growth factors and other cytokines that are known to stimulate regenerative processes of body tissues like bone, ligaments, skin, hair and much more. It is obtained from the patient's own blood after red blood cells (RBC) have been removed and the platelets are concentrated in a small volume of plasma to 4-8 times (or more) its normal count in blood.

Platelet Poor Plasma (PPP) is used in many laboratory tests (including detecting antibodies in patient blood) and is obtained by removing from whole blood all cellular elements (red blood cells, platelets, white blood cells etc.).

The central part in the process of PRP preparation is prompt separation of blood fractions. Undisturbed blood left alone will separate on its own, due to gravity forces into density layers, but usually a centrifuge is used to accelerate the process.

Generic Process

Traditionally PRP is obtained in several steps using a two-spin method. In the first step the patient's whole blood is drawn to a fluid collection tube. See,FIGS. 1A and 1B. Next, the tube undergoes a first spin cycle (hereinafter “first spin”) in the centrifuge and the whole blood is separated into three broad fractions: red blood cells (RBC), buffy coat (leukocytes and platelets) and plasma. See,FIG. 1C.

In the next step, the buffy coat and plasma, collectively Platelet Enriched Plasma (PEP), which contains slightly concentrated platelets (up to two times normal blood count) are transferred to a second tube (FIG. 1D) for a second spin to further concentrate the platelets. After the second spin cycle (hereinafter “second spin”) the PEP will separate into Platelet Pallet (PP) and plasma with very few (substantially no) platelets called Platelet Poor Plasma (PPP). See,FIG. 1E.

In the final step, about two-thirds to three-quarters (⅔-¾) of PPP is removed. It contains essentially no cellular elements and can be used in various laboratory tests. The remaining plasma is mixed with Platelet Pallet. The resulting mixture is called PRP with platelet concentration of 4-8 (or more) times normal blood count. See,FIG. 1F.

Prior Art Shortcomings

After the first spin in the above-described process, a syringe is used to aspirate the plasma and buffy coat through a needle, in order to transfer both into a second tube for a second spin. However, in order to reach the buffy coat located just above the RBC, a small diameter syringe and/or a long needle, are required. Most importantly, it is very difficult to aspirate all buffy coat (layered on top of RBC), without also aspirating a significant quantity of the undesired RBC.

Most commonly, commercial PRP tubes containing separating gel, are used to collect blood. See,FIGS. 2A and 2B. While this PRP preparation process is somewhat easier, it also is more costly. The separating gel acts as a semi-permeable membrane. During centrifugation, RBC is forced to pass through the gel and collects beneath it, which leaves plasma and buffy coat physically separated above it. After centrifugation, the gel functions as a barrier, allowing the tube to be tilted or turned up-side down (to facilitate aspiration of the buffy coat and plasma), without causing the RBC to mix with the buffy coat and plasma. The mixture of buffy coat and plasma is called Platelets Enriched Plasma (PEP). In the next step, a syringe is used to aspirate the PEP through a needle, in order to transfer it into a second tube to undergo a second spin. See,FIGS. 2C and 2D.

Regardless of whether tubes with separating gel are used, after the first spin plasma and buffy coat (PEP) need to be transferred to another tube for a second spin, to further concentrate the platelets. Because of the relative complexity of those additional steps involved, the medical practitioners often choose to settle for PEP in their procedures, or in some cases proceed with the suboptimal PRP obtained by removing the excess plasma from the single spin.

PRESENT INVENTION BENEFITS

The present invention addresses the shortcomings of the existing methods for transferring fluid density layers from specimen tubes into syringes. With respect to PRP preparation, it is a system which makes it possible to transfer a chosen layer of blood fraction after centrifugation, from a fluid collection tube to a syringe or a syringe-like receptacle, without the need for needles and without relying solely on negative pressure aspiration.

The present invention also eliminates the need for separating gel, because it allows a precise transfer of plasma and buffy coat to a syringe or syringe-like device, with minimal RBC contamination. This is possible because the transfer of the lightest density fluid, which has a tendency to stay on top of heavier density fluids, always takes place first, and the quantity being transferred can be easily controlled.

Eliminating the separating gel also eliminates the possibility of contaminating the plasma with gel particles; it also significantly reduces the cost to the operator as well as to the patient. Elimination of needles diminishes the risk of sample contamination and the risk of accidental needle poke that could lead to the transmission of infectious diseases (bacteria, viruses) to the operator.

In addition to eliminating the needles, the present invention also eliminates the need for a second fluid collection tube and for the transfer syringe (used to transfer the product of the first spin (PEP) from the first tube into the second tube to perform the second spin).

The core parts of the invention are a tube seal that eliminates the need for needles and renders the separating gel unnecessary, and a barrel that replaces both the transfer syringe and the second-spin tube.

SUMMARY OF INVENTION

Example 1: A device for extracting plasma from a fluid collection tube containing a sample of whole blood which has been centrifuged to form a red blood cell layer, a buffy coat layer and a plasma layer, the device comprising:

a tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the tubular barrel forming a tip at a distal end;

a barrel seal movingly seated within the lumen of the tubular barrel, the barrel seal closing and sealing the proximal end of the tubular barrel;

a tube seal having a proximal end, a distal end, and a lumen extending therebetween, the proximal end having a frustoconical or chamfered face, the tube seal having an outer diameter sized to sealingly engage with an inner surface of the fluid collection tube, and an inner diameter sized to sealingly engage with an outer surface of the tip of the tubular barrel, the tube seal mounted on the tubular barrel such that the tip of the tubular barrel extends into the tube seal lumen;

wherein as the tubular barrel is advanced into the fluid collection tube, the tube seal engages with inner walls of the fluid collection tube and the outer surface of the tip of the tubular barrel, and the barrel seal is pushed proximally by plasma flowing from the fluid collection tube into the lumen of the tubular barrel.

Example 2: The tube seal of Example 1, wherein the tube seal is an elastomeric member having at least one sealing ring provided on the exterior surface thereof.

Example 3: The device of Examples 1-2, further comprising an elongate rod having an outer diameter which is smaller than a diameter of the lumen of the tubular barrel, the rod being removably inserted into the lumen of the tubular barrel.

Example 4: The device of Example 3, further comprising:

a tubular casing having a closed proximal end and an open distal end and a lumen extending between the closed proximal end and the open distal end;

a diameter of the rod being less than a diameter of the lumen of the tubular casing;

at least a portion of the rod coaxially received within the tubular casing, with a gap G defined between an inner surface of the tubular casing and an exterior surface of the rod;

a portion of the tubular barrel sidewall being coaxially received in the gap G.

Example 5: The device of Example 1, further comprising a barrel cap configured to sealingly engage with the tip of the tubular barrel and engaging an exterior surface of the tip and/or having a plug which fits into the lumen of the tip.

Example 6: A kit for extracting plasma from a fluid collection tube containing a centrifuged sample of whole blood which has been centrifuged to form a red blood cell layer, a buffy coat layer and a plasma layer, the kit comprising a tube seal having a lumen therethrough, the tube seal sized to movably engage with an inner surface of the fluid collection tube, the lumen of tube seal being sized to sealingly engage with a tip of a syringe-like device.

Example 7: The kit of Example 6, further comprising:

a tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the tubular barrel forming a tip at a distal end; and

a barrel seal movingly seated within the lumen of the tubular barrel, the barrel seal closing and sealing the proximal end of the tubular barrel;

wherein the tip of the tubular barrel sized to snugly fit into and sealingly engage with the lumen of the tube seal;

wherein as the tubular barrel is advanced into the fluid collection tube, the tube seal engages with the inner surface of the fluid collection tube and engages with an outer surface of the tip of the tubular barrel, and the barrel seal is pushed proximally by plasma flowing from the fluid collection tube into the lumen of the tubular barrel.

Example 8: The kit of Example 7, comprising an elongate rod having an outer diameter which is smaller than a diameter of the lumen of the tubular barrel, the elongate rod being removably inserted into the lumen of the tubular barrel.

Example 9: The kit of Example 8, further comprising a tubular casing having a closed proximal end and an open distal end and a lumen extending between the closed proximal end and the open distal end.

Example 10: The kit of Example 6-9, wherein the tube seal is removably mounted to the tip of the tubular barrel.

Example 11: The kit of Example 10, further comprising a barrel cap configured to sealingly engage with the tip of the tubular barrel and engaging an exterior surface of the tip and/or having a plug which fits into the lumen of the tip.

Example 12: A tube seal, comprising: an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a lumen extending therebetween, the proximal end having a frustoconical or chamfered face, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of a fluid collection tube, the lumen of tube seal being sized to sealingly engage with a tip of a syringe-like device.

Example 13: The tube seal of Example 12, further comprising at least one sealing ring provided on the exterior surface of the elastomeric member.

Example 14: A method for creating for extracting plasma from a fluid collection tube containing a sample of whole blood which has been centrifuged to form a red blood cell layer, a buffy coat layer and a plasma layer, comprising the steps of:

providing a tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the tubular barrel forming a tip at a distal end, a barrel seal movingly seated within the lumen of the tubular barrel, the barrel seal closing and sealing the proximal end of the tubular barrel, and a tube seal having a proximal end, a distal end, and a lumen extending therebetween, the proximal end having a frustoconical or chamfered face, the tube seal having an outer diameter sized to sealingly engage with an inner surface of the fluid collection tube, and an inner diameter sized to sealingly engage with an outer surface of the tip of the tubular barrel, the tip of the tubular barrel extending into the tube seal lumen;

inserting the distal end of the tubular barrel into the fluid collection tube such that the tube seal engages with an inner surface of the fluid collection tube;

as the tubular barrel is advanced into the fluid collection tube pushing the tube seal distally, plasma will flow through the tube seal lumen into the lumen of the tubular barrel and the barrel seal is pushed proximally by the plasma flowing into the tubular barrel, wherein the tubular barrel is advanced until red blood cells just start to enter into the tubular barrel, at which point the plasma and the buffy coat have been transferred to the tubular barrel;

the tubular barrel is withdrawn from the fluid collection tube, leaving the tube seal engaged within the fluid collection tube along with the remaining red blood cells; and

the tubular barrel containing the plasma and buffy coat is centrifuged to separate the plasma into platelet poor plasma (PPP) and platelet pallet.

Example 15: The method of Example 14, comprising the steps of:

providing a first syringe having a first plunger movably mounted therein;

fluidically coupling a tip of the first syringe to the tip of the first tubular barrel; and

transferring between ⅔ and ¾ of the platelet poor plasma from the tubular barrel to the attached syringe by advancing a distal end of a rod distally within the lumen of the tubular barrel toward the tip of the tubular barrel pushing the barrel seal distally with the rod and/or retracting the first syringe plunger.

Example 16: The method of Example 15, comprising the steps of:

disconnecting the syringe containing the platelet poor plasma from the tip of the tubular barrel, and discarding the syringe containing the platelet poor plasma;

providing a second syringe having a second plunger movably mounted therein;

connecting the second syringe to the tip of the tubular barrel; and

transferring the platelet poor plasma and buffy coat back-and-forth between the tubular barrel and the second syringe thereby mixing the platelet poor plasma and the buffy coat to create platelet rich plasma (PRP).

Example 17: A method for creating PRP, comprising the steps:

providing a device according to Example 3;

inserting the distal end of the tubular barrel with the tube seal mounted thereon into the fluid collection tube;

advancing the tubular barrel and tube seal distally into the fluid collection tube, wherein plasma will flow proximally through the lumen of the tube seal into the tubular barrel pushing the barrel seal proximally, wherein the tubular barrel should be advanced until red blood cells just start to enter into the tube seal; and

withdrawing the tubular barrel from the fluid collection tube leaving the tube seal in the fluid collection tube with the remaining red blood cells.

Example 18: The method of Example 17, further comprising the steps:

centrifuging the tubular barrel to separate the plasma and buffy coat into platelet poor plasma and platelet pallet;

providing a first syringe having a first plunger movably mounted therein;

fluidically coupling the first syringe to the tip of the tubular barrel;

inserting the rod into the proximal end of the tubular barrel, and advancing the rod distally within the lumen of the tubular barrel toward the tip pushing the barrel seal distally and transferring any residual air and ⅔-¾ of the platelet poor plasma to the first syringe, or instead of advancing the rod, retracting the plunger of the first syringe to transfer of air and platelet poor plasma;

disconnecting the first syringe with air and the platelet poor plasma from the tip of the tubular barrel;

providing a second syringe having a second plunger movably mounted therein; and

fluidically coupling the second syringe with the tip of the tubular barrel, and transferring the platelet pallet and remaining plasma back-and-forth between the tubular barrel and the second syringe.

Example 19: The method of Example 17, wherein after step of inserting the distal end of the tubular barrel with the tube seal mounted thereon into the fluid collection tube, gently removing the tubular barrel with a twisting motion leaving the tube seal engaged with the lumen of the fluid collection tube, placing the proximal end of the tubular barrel in abutment with the tube seal and advancing the tubular barrel to push or advance the tube seal until it contacts the plasma, withdrawing the proximal end of the tubular barrel from the fluid collection tube, and placing the distal end of the tubular barrel in sealing engagement with the tube seal.

Example 20: A method for creating PRP, comprising the steps of:

providing a first syringe having a first plunger movably mounted therein, the first syringe containing a specimen of whole blood;

providing a first tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the first tubular barrel forming a first tip at a distal end, a first barrel seal movingly seated within the lumen of the first tubular barrel, the first barrel seal closing and sealing the proximal end of the first tubular barrel;

fluidically coupling the first syringe to the tip of the first tubular barrel;

transferring the specimen of whole blood from the first syringe into the first tubular barrel by advancing the first plunger within the first syringe, wherein the first barrel seal is pushed toward the proximal end of the first tubular barrel by the blood entering the first tubular barrel;

disconnecting and discarding the first syringe;

centrifuging the first tubular barrel with the whole blood, separating the whole blood into a layer of red blood cells, buffy coat, and plasma;

providing a second syringe having a second plunger movably mounted therein;

fluidically coupling the second syringe to the tip of the first tubular barrel; and

transferring the plasma and buffy coat from the first tubular barrel into the second syringe by retracting the second plunger within the second syringe or by advancing the first barrel seal within the first tubular barrel using a rod.

Example 21: The method of Example 20, comprising:

disconnecting and discarding the first tubular barrel;

providing a second tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the second tubular barrel forming a second tip at a distal end, a second barrel seal movingly seated within the lumen of the tubular barrel, the second barrel seal closing and sealing the proximal end of the second tubular barrel;

fluidically coupling the second syringe to the tip of the second tubular barrel;

transferring the plasma and buffy coat from the second syringe into the second tubular barrel; and

centrifuging the second tubular barrel to separate the plasma and buffy coat into its constituent platelet poor plasma and platelet pallet.

Example 22: The method of Example 21, comprising:

providing a third syringe having a third plunger movably mounted therein;

fluidically coupling the third syringe to the tip of the second tubular barrel; and

transferring any residual air and ⅔-¾ of the platelet poor plasma into the third syringe by either advancing the distal end of the rod within the lumen of the second tubular barrel toward the tip or retracting the third plunger of the third syringe.

Example 23: The method of Example 22, comprising:

disconnecting and discarding the third syringe with the platelet poor plasma;

providing a fourth syringe having a fourth plunger movably mounted therein;

fluidically couple the fourth syringe with the tip of the second tubular barrel; and

transferring the platelet pallet and remaining platelet poor plasma back-and-forth between the second tubular barrel and the fourth syringe to dislodge the platelet pallet from the fourth syringe and mix it with remaining plasma thereby creating plasma rich platelets.

Example 24: A method for creating PRP, comprising the steps of:

providing a fluid collection tube containing a sample of whole blood which has been centrifuged to separate the whole blood into layers of red blood cells, buffy coat, and plasma;

providing a first tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the first tubular barrel forming a tip at a distal end, a first barrel seal movingly seated within the lumen of the first tubular barrel, the first barrel seal closing and sealing the proximal end of the tubular barrel;

inserting the tip of the first tubular barrel with a first tube seal mounted thereon into the fluid collection tube;

advancing the first tubular barrel within the fluid collection tube, wherein as the first tubular barrel is advanced distally into the fluid collection tube, plasma enters into the first tubular barrel and pushes the first barrel seal proximally, wherein the first tubular barrel is advanced until ¾ of the plasma has been transferred into the first tubular barrel, leaving the red blood cells, buffy coat, and ¼ of the plasma;

disconnecting and discarding the first tubular barrel with the plasma;

providing a second tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the second tubular barrel forming a tip at a distal end, a second barrel seal movingly seated within the lumen of the second tubular barrel, the second barrel seal closing and sealing the proximal end of the second tubular barrel;

inserting the tip of the second tubular barrel into the fluid collection tube;

advancing the second tubular barrel such that the tip of the second tubular barrel sealingly engages with the first tube seal and continuing to advance the second tubular barrel distally into the fluid collection tube until all of the plasma and the buffy coat are transferred into the second tubular barrel, leaving the red blood cells;

removing the second tubular barrel from the fluid collection tube;

providing a second syringe having a second plunger movably mounted therein;

fluidically coupling the second syringe with the tip of the second tubular barrel; and

transferring the plasma and buffy coat back-and-forth between the second tubular barrel and the second syringe to mix the buffy coat with remaining plasma thereby creating plasma rich platelets.

Example 25: A method for creating PRP, comprising the steps of:

providing a fluid collection tube containing a sample of whole blood which has been centrifuged to separate the whole blood into layers of red blood cells, buffy coat, and plasma;

providing a first syringe having a plunger movably mounted therein;

providing a first tube seal on a tip of the first syringe;

inserting the tip of the first syringe with the first tube seal mounted thereon into the fluid collection tube;

advancing the first syringe within the fluid collection tube, wherein as the first syringe is advanced distally into the fluid collection tube, plasma enters into the first syringe and pushes the first plunger proximally, wherein the first syringe is advanced until % of the plasma has been transferred into the first syringe;

disconnecting and discarding the first syringe while leaving the first tube seal mounted within the fluid collection tube;

providing a second syringe having a second plunger movably mounted therein;

inserting a tip of the second syringe into the fluid collection tube;

advancing the second syringe until it sealingly engages with the first tube seal and continuing to advance the second syringe distally into the fluid collection tube until all of the plasma and the buffy coat are transferred into the second syringe; and

disconnecting the second syringe from the fluid collection tube, and discarding the fluid collection tube.

Example 26: A method for transferring a first layer of fluid from a fluid specimen tube containing at least two layers of fluid where each fluid had a different specific gravity, using the device of Example 1, comprising the steps of:

providing a tubular barrel having sidewall surrounding a lumen which extends between proximal and distal ends thereof, the tubular barrel forming a tip at a distal end, a barrel seal movingly seated within the lumen of the tubular barrel, the barrel seal closing and sealing the proximal end of the tubular barrel, and a tube seal having a proximal end, a distal end, and a lumen extending therebetween, the proximal end having a frustoconical or chamfered face, the tube seal having an outer diameter sized to sealingly engage with an inner surface of the fluid collection tube, and an inner diameter sized to sealingly engage with an outer surface of the tip of the tubular barrel, the tip of the tubular barrel extending into the tube seal lumen;

inserting the distal end of the tubular barrel into the fluid collection tube such that the tube seal engages with an inner surface of the fluid collection tube;

as the tubular barrel is advanced into the fluid collection tube pushing the tube seal distally, fluid1will flow through the tube seal lumen into the lumen of the tubular barrel and the barrel seal is pushed proximally by the plasma flowing into the tubular barrel, wherein the tubular barrel is advanced until fluid2just starts to enter into the tubular barrel, at which point the fluid1has been transferred to the tubular barrel;

the tubular barrel is withdrawn from the fluid collection tube, leaving the tube seal engaged within the fluid collection tube along with fluid2.

