Connector for creating platelet rich plasma

Method for transferring one or more portions of fluid from a specimen tube, comprising: providing an elongate connector comprising an elongated tube having a lumen or through-hole extending between proximal and distal ends thereof, a Luer-compatible female taper provided on the proximal end of the connector, a flange provided proximate the distal end of the connector; providing a tube seal mounted on the distal end of the connector, the tube seal comprising an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a through-hole extending therebetween, the distal end having a frustoconical or chamfered face forming a funnel, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of the specimen tube; advancing the distal end of the connector and the tube seal into the specimen tube, the funnel directing the first layer into the through-hole of the connector.

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 and1B. 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 and2B. 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 and2D.

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 and a barrel, both of which allow transfer (or extraction) of the plasma (PPP/PEP) from the tube, without use of needles, directly into the barrel, eliminating error associated with precisely positioning the needle within a thin layer of buffy coat. The barrel, having diameter allowing it to be advanced into the tube, is serving as a perfect receptacle for acquiring the specimen from the tube, and having no flanges is perfect for insertion into the centrifuge. After the second spin, the barrel featuring a female Luer tip (Luer taper), allows easy transfer of plasma directly into the injection syringe, without need for connectors.

In contrast, the conventional preparation of PEP/PRP with blood drawn into the tube, normally ends right after the first centrifugation with end result being PEP or an inferior single-spin PRP, the present invention allows the continuation of the process to the second centrifugation to obtain optimal two-spin PRP.

SUMMARY OF INVENTION

Example 1: A method for transferring one or more portions of fluid from a specimen tube, comprising:providing a specimen tube containing a fluid specimen;centrifuging the specimen tube to separate the fluid specimen into at least a first layer having a density D1 and a second layer having a density D2 such that D2>D1;providing an elongate connector, where the connector comprises an elongated tube having a lumen or through-hole extending between proximal and distal ends thereof, a Luer-compatible female taper provided on the proximal end of the connector, a flange provided proximate the distal end of the connector;providing a tube seal mounted on the distal end of the connector, the tube seal comprising an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a through-hole extending therebetween, the distal end having a frustoconical or chamfered face forming a funnel, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of the specimen tube;advancing the distal end of the connector and the tube seal into the specimen tube, the funnel directing the first layer into the through-hole of the connector, wherein the distal end of the connector and the tube seal are advanced until the first layer at least partially fills the comprises, through-hole of the connector, thereby de-airing the connector;providing a first syringe and connecting the first syringe to the female taper of the connector; andadvancing the distal end of the connector and the tube seal and the connected first syringe into the specimen tube until the first layer is transferred into the first syringe.

Example 2: The method of Example 1 wherein the distal end of connector is provided with a Luer-compatible male or female taper.

Example 3: The method of Example 1, wherein:the fluid specimen is blood;the step of centrifuging the specimen tube separates the blood into a layer of plasma, a layer of buffy coat, and a layer of RBC, wherein the plasma has a density D1, the buffy coat has a density D2 and the RBC has a density D3 such that D3>D2>D1;advancing the distal end of the connector and the tube seal and the connected first syringe into the specimen tube until the plasma or the plasma and buffy coat are transferred into the first syringe.

Example 4: The method of Example 3, whereinbefore the step of providing the first syringe, providing a second syringe and connecting the second syringe to the female taper of the connector;advancing the distal end of the connector and the tube seal and the connected second syringe into the specimen tube until between ½ and ¾ of the plasma is transferred into the second syringe; anddisconnecting the second syringe.

Example 5: A connector, comprising:an elongate tubular member having a proximal end, a distal end, and a lumen or through-hole extending therebetween, the tubular member formed of at least partially of a transparent or semi-transparent material;a first Luer-compatible female taper provided on the proximal end of the connector; anda flange provided proximate the distal end of the connector.

Example 6: The connector of Example 5, a second Luer-compatible male or female taper provided on the distal end of the connector.

Example 7: The connector of Example 5 further comprising a tube seal mounted on the distal end of the connector, the tube seal including an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a through-hole extending therebetween, the distal end having a frustoconical or chamfered face forming a funnel, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of a specimen tube.

Example 8: A method for transferring one or more portions of fluid from a specimen tube into a syringe, comprising:providing a specimen tube containing a tube seal and a fluid specimen, wherein tube seal includes an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a through-hole extending therebetween, the distal end having a frustoconical or chamfered face forming a funnel, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of the specimen tube;centrifuging the specimen tube to separate the fluid specimen into at least a first and a second layer of fluid, where the first layer of fluid has a density D1 and the second layer of fluid has a density D2 such that D2>D1;providing an elongate connector, where the connector comprises an elongated tube having a lumen or through-hole extending between proximal and distal ends thereof, a Luer-compatible female taper provided on the proximal end of the connector, a flange provided proximate the distal end of the connector;advancing the distal end of the connector into the specimen tube such that the distal end of the connector fluidically couples with a proximal end of the tube seal, the funnel directing the first layer of fluid into the through-hole of the connector, wherein the distal end of the connector and the tube seal are advanced until the first layer of fluid fills the through-hole of the connector, thereby de-airing the connector;providing a first syringe and connecting the first syringe to the female taper of the connector; andadvancing the distal end of the connector and the tube seal and the connected first syringe into the specimen tube until the first layer of fluid is transferred into the first syringe.Example 9: A method for making platelet enriched plasma, comprising:providing a specimen tube containing a centrifuged specimen of blood containing distinct layers of plasma, buffy coat and RBC;providing an elongate connector, where the connector comprises an elongated tube having a lumen or through-hole extending between proximal and distal ends thereof, a Luer-compatible female taper provided on the proximal end of the connector, a flange provided proximate the distal end of the connector;providing a tube seal mounted on the distal end of the connector, the tube seal comprising an elastomeric member having a longitudinal axis, a proximal end, a distal end, and a through-hole extending therebetween, the distal end having a frustoconical or chamfered face forming a funnel, the elastomeric member having an outer diameter sized to sealingly engage with an inner surface of the specimen tube;advancing the distal end of the connector and the tube seal into the specimen tube, the funnel directing the plasma into the through-hole of the connector, wherein the distal end of the connector is advanced until the plasma at least partially fills the comprises, through-hole of the connector, thereby de-airing the connector;providing a first syringe and connecting the first syringe to the female taper of the connector; andadvancing the distal end of the connector and the connected first syringe into the specimen tube until the plasma and buffy coat are transferred into the first syringe.

DETAILED DESCRIPTION

Described herein is a tube seal and a barrel, which may be used to facilitate the removal of fluid layers having different density. The examples disclosed herein are described with reference to centrifuging whole blood in order to separate it into its constituent components, each of which has a different density. However, one of ordinary skill in the art will appreciate that the invention is not limited to the constituent layers of whole blood. For instance, the invention can be used in situations/applications when a particular fraction of fluid has to be removed and transferred from one specimen tube to another syringe. For example, the invention may be used in the process of obtaining adipose derived tissue stromal vascular fraction (AD-tSVF) from a body's fat aspirate, after emulsification and separation into density layers by centrifugation.

The Tube Seal

The tube seal may be sized to fit commercially available fluid collection tubes.FIG.3Ashows the tube seal108of the present invention inserted into a conventional fluid collection tube602.FIG.3Bshows the tube seal108inserted into a conventional fluid collection tube602with an anticoagulant,FIG.3Cshows the tube seal108inserted into a conventional fluid collection tube602with both an anticoagulant and a separating gel.

FIG.4Ashows how the tube seal108is mounted on a distal end of a conventional syringe180.

FIG.4Bshows how the syringe180, with the tube seal108mounted on a distal end thereof, is inserted into the mouth of a conventional fluid collection tube602.

FIGS.4C,4Dshow the syringe180with the tube seal108mounted on a distal end thereof being moved distally within the conventional fluid collection tube602until a portion of the fluid within the fluid collection tube602is transferred into the syringe180.

In some examples it may be desirable to use a tube seal dispenser to insert the tube seal into the fluid collection tube602instead of manually placing the tube seal in the tube with one's hand, or mounting the tube seal on the distal end of the syringe180. A method of using a dispenser to insert the tube seal into the fluid collection tube602using a dispenser is shown inFIGS.5A-5D.

FIG.5Ashows how the tube seal108is mounted on a distal end of a dispenser rod.

FIG.5Bshows how the dispenser rod with the tube seal108mounted on a distal end thereof is inserted into the mouth of a conventional fluid collection tube602.

FIGS.5C,5Dshow how the syringe180is placed in abutment or engagement with the tube seal inside of the fluid collection tube602, and how the syringe is moved distally within the conventional fluid collection tube602until a portion of the fluid within the fluid collection tube602is transferred into the syringe180.

The tube seal108(FIGS.7A,7B) has a proximal end face108P and a distal end face108D. In some examples, the end face108P,108D may have a shape108-2,108-3configured to compliment or mattingly engage the tapered end face of a conventional syringe. The tube seal108may be formed of resilient, elastomeric material such as rubber.

An outer surface of the tube seal108may have a shape which mirrors the shape of the inner surface of the fluid collection tube thereby ensuring sealing engagement therebetween. In some examples, one or more raised sealing rings108S spanning the outer circumference (surface) of the tube seal may be provided. In the example shown inFIGS.3A-3C, the fluid collection tube602and the tube seal108each have a circular cross-section; however, these components may have any complimentary shaped cross-section.

As best seen inFIGS.7A,7B, the tube seal108has a lumen108L. In some examples, the lumen108L has a dual taper with a first taper108-1extending from the proximal end face108P towards the distal end face108D and a second taper108-2extending from the distal end face108D towards the proximal end face108P. See,FIG.7B. Additionally, the inner wall of the tube seal108which bounds or surrounds the lumen, may be tapered. In the example depicted inFIG.7B, the inner wall is tapered such that the lumen108L is wider at proximal end108P than at distal end108D. The inner wall may have a dual taper as desired. The tube seal108may be formed of an elastomeric material.

In some examples, the proximal end of the tube seal108is of a conical or funnel shape to direct any residual blood through the lumen108L to the other side of the tube seal108.

The tube seal108is sized to sealingly engage the inner surface of a fluid collection tube. An outer surface of the tube seal108may have a shape which mirrors the shape of the inner surface of the fluid collection tube thereby ensuring sealing engagement therebetween.

In some examples, the proximal end face108P of the tube seal108may have a shape which compliments or mattingly engages the tapered end face of the barrel106.

In some examples, the proximal end of the tube seal108is of a conical or funnel shape to direct any residual blood through the lumen108L to the other side of the tube seal108.

The tube seal108may be provided by itself or as part of a kit or assembly. The kit may include a fluid collection tube, cap for fluid collection tube, and tube seal. In some examples, the fluid collection tube will be prefilled with an anticoagulant. In some examples, the fluid collection tube will be prefilled with an anticoagulant and a separating gel. In some examples, the tube seal is preloaded into the fluid collection tube. In some examples, the kit may include a dispenser for introducing the tube seal into the tube. The tube seal may also be pre-mounted on the tip of a conventional syringe or any syringe-like device.

Throughout this disclosure, the term syringe or syringe-like device should be understood to encompass any conventional syringe having a plunger slidingly received within a tubular barrel. The plunger includes an elastomeric member on a distal end thereof which sealingly engages with the interior circumference of the tubular barrel. The syringe may be used to either inject fluid by advancing the plunger distally, or to aspirate fluids by retracting the plunger proximally.

As will be explained below, the tube seal108may be used as a connector and adapter for transferring fluids between a fluid collection tube and a syringe, and provides a fluidic connection between the tube and the syringe. In some examples the tube seal facilitates fluid transfer from the tube to the syringe due to a pressure rise in the tube (caused by advancing the syringe distally and exerting a pressure against the tube seal)FIGS.8A-8D.FIG.8Ashows a fluid collection tube602containing a volume V1 of fluid (at ambient pressure A), a tube seal108and a syringe180.FIG.8Bshows the fluid collection tube602and the syringe180ofFIG.8Aafter the syringe180has been advanced distally into the fluid collection tube602thereby increasing the pressure of the volume of fluid V1 (in the moment before fluid is transferred into the syringe due to the pressure gradient therebetween).FIG.8Cshows the fluid collection tube602and syringe180ofFIG.8Bafter a volume V2 has been transferred from the fluid collection tube602to the syringe180due to the pressure gradient therebetween (in the moment before the pressure in the fluid collection tube602goes back to ambient.FIG.8Dshows the fluid collection tube602and syringe180ofFIG.8Cafter a volume V2 has been transferred from the fluid collection tube602to the syringe180due to the pressure gradient therebetween, after the pressure in the fluid collection tube602goes back to ambient.

In some examples the tube seal facilitates fluid transfer from the tube to the syringe due to a pressure drop in the connected syringe (caused by retracting the plunger proximally and creating suction in the syringe).FIG.9Ashows a fluid collection tube602containing a volume V1 of fluid (at ambient pressure A), a tube seal108and a syringe180.FIG.9Bshows the fluid collection tube602and the syringe180ofFIG.9Aafter the plunger of syringe180has been retracted proximally thereby decreasing the pressure within the syringe180below ambient (in the moment before fluid is transferred into the syringe due to the pressure gradient therebetween).FIG.9Cshows the fluid collection tube602and syringe180ofFIG.9Bafter a volume V2 has been transferred from the fluid collection tube602to the syringe180due to the pressure gradient therebetween (in the moment before the pressure in the syringe180goes back to ambient.FIG.9Dshows the fluid collection tube602and syringe180ofFIG.9Cafter a volume V2 has been transferred to the fluid collection tube602to the syringe180due to the pressure gradient therebetween, after the pressure in the syringe180goes back to ambient.

Generic Process of Fluid Transfer

Turning now toFIGS.10A-10F, a method for transferring at least one layer fluid from a collection tube602containing two or more layers of fluid, where each layer of fluid has a different specific gravity will be explained. The generic process used to transfer fluid from a fluid collection tube602to a syringe180utilizing the tube seal108will be explained.

InFIG.10A, a fluid collection tube602containing a fluid specimen is centrifuged to separate the fluid specimen into its constituent components by density: layer1, layer2, and layer3. One of ordinary skill in the art will appreciate that the method may be used with any number of different density fluid layers.

InFIG.10B, cap602C is removed from the fluid collection tube602, and tube seal108is inserted into the mouth of the fluid collection tube602. One of ordinary skill in the art will appreciate that the tube seal108may be inserted into the fluid collection tube602prior to the centrifuging step illustrated inFIG.10A. Or the fluid collection tube602may be equipped or supplied with the tube seal already inside the tube prior to insertion of the fluid.

InFIGS.10C,10D, a syringe180(without a needle) is inserted into the mouth of the fluid collection tube602such that the distal tip of the syringe180is placed in sealing engagement with the tube seal108.

InFIG.10E, as the syringe180is advanced distally into the fluid collection tube602, fluid1is displaced from the fluid collection tube602into the syringe180. The tube seal108seals the fluid collection tube602with the syringe, enabling the transfer of fluid. It should be appreciated that the plunger of the syringe180may be retracted instead of or in addition to advancing the syringe180distally into the fluid collection tube602.

IfFIG.10F, the syringe180containing fluid1may be removed from the tube seal108upon the transfer or displacement of the desired quantity of fluid1. One of ordinary skill will appreciate that the syringe180may be removed from the tube seal108and at any time, and a new syringe or syringe-like device180may be introduced to transfer desired quantities of the remaining fluids1,2,3.

Example PRP Extraction Using the Tube Seal with Ordinary Syringes (One-Spin)

Turning now toFIGS.11A-11J, a method for transferring fluid from a fluid collection tube602to a syringe180utilizing the tube seal108will be explained. The example process pertains to the creation of platelet rich plasma but one of ordinary skill in the art will appreciate that the tube seal may be used generally to facilitate fluid transfer.

InFIG.11A, a fluid collection tube602containing a specimen of whole blood is centrifuged to separate the whole blood into its constituent components by density: red blood cells (RBC), buffy coat, and plasma.

InFIG.11B, cap602C is removed from the fluid collection tube602, and tube seal108is inserted into the mouth of the fluid collection tube602. One of ordinary skill in the art will appreciate that the tube seal108may be inserted into the fluid collection tube prior to the centrifuging step illustrated inFIG.11A. Or the tube may be equipped or supplied with the tube seal already inside the tube prior to fluid collection.

InFIGS.11C,11D, a syringe180(without a needle) is inserted into the mouth of the fluid collection tube602such that the distal tip of the syringe180is placed in sealing engagement with the tube seal108.

InFIG.11E, as the syringe180is advanced distally into the fluid collection tube602, plasma is displaced from the fluid collection tube602into the syringe180until between ⅔ and ¾ (by volume) of the plasma is transferred into the syringe. The tube seal108seals the fluid collection tube602with the syringe, enabling the transfer of fluid. It should be appreciated that the plunger of the syringe180may be retracted instead of or in addition to advancing the syringe180distally into the fluid collection tube602.

InFIG.11F, the syringe180with the plasma is discarded, and a fresh (empty) syringe180is placed into sealing engagement with the tube seal108.

InFIGS.11G,11H, the syringe180and the tube seal108are advanced distally such that the remaining plasma and the buffy coat (collectively PRP) are transferred into the syringe180. Again, the tube seal108seals the fluid collection tube602and the syringe180, enabling the transfer of fluid. Also, the plunger of the syringe180may be retracted instead of or in addition to advancing the syringe180distally into the fluid collection tube602.

InFIGS.11I and11J, the syringe180with the PRP is withdrawn from the fluid collection tube602, and a needle is attached to the syringe.

The aforementioned process using the tube seal108is an improvement over the conventional process for creating PRP, because it eliminates the needles, eliminates separating gel, and does not solely rely on aspiration.

Also disclosed is a system and kit for obtaining PRP using the tube seal108, as well as associated methods for separating platelet rich plasma (“PRP”) from whole blood. The system, kit, and associated methods of the present invention address several shortcomings of conventional PRP kits in that it reduces the number of components needed, eliminates the need for a separating gel, in some examples enables separation of PRP from the tube after a single centrifuge spin cycle, eliminates the need for needles thereby reducing the risk of accidental needle stick, is simpler to use, and reduces the risk of sample contamination.

The Barrel

As will be explained below, the barrel106is a fluid transfer receptacle equipped with a piston-like barrel seal108. The barrel is sized to fit within the lumen of a standard fluid collection tube. The barrel features a tip, whose outer surface is capable of sealingly engaging with the tube seal, and an inner surface capable of sealingly engaging with a male Luer connector of a syringe. The below mentioned process using the tube seal108with the barrel106, is an improvement over the conventional process for creating PRP, because while the tube seal eliminates the needles and separating gel and does not solely rely on aspiration, the barrel replaces both the transfer syringe and the second-spin tube.

The barrel seal108may be formed of an elastomeric material which may be the same material used to form the tube seal.

FIG.12: The barrel106is an elongate hollow tube having sidewalls which surround a central lumen106L. A proximal end106P of the barrel is open and communicates with the lumen106L. A distal portion of the barrel gradually tapers narrower to a kind of Luer tip106T. In some examples the distal end106D is conical shaped. The tip106T tappers narrower. A width of the sidewall of the barrel106is less than gap G, and a diameter of lumen106L is greater than the diameter of the rod103. The distal end of the rod103fits into the proximal end of the barrel106and the rod103can be loosely inserted into the lumen106L.

The barrel106may have the general appearance of a conventional syringe but in some examples differs from a conventional syringe in several key aspects. One notable difference is that barrel106is not meant to be equipped with a needle. The outer side of the tip106T forms an oversized male to sealingly engage with a tube seal108, and cannot accommodate a needle. The inner side of the tip106T forms a female Luer connection configured to sealingly engage with a male Luer connection of a regular syringe. Another notable difference is that the proximal end106P of the barrel106lacks the flanges or gripping portions provided on conventional syringes which are used to assist advancing the plunger. The barrel106is never used to inject anything. Lacking a flange and without the plunger rod, the barrel106is configured to be securely received within a conventional centrifuge device.

The barrel seal104(FIGS.13,16) is movably provided within the lumen106L and will only move when pushed proximally by fluid entering the barrel106through the Luer tip106T or when advanced distally by the rod103.

As best seen inFIGS.17A,17Bthe rod103fits within lumen106L while the barrel106fits in the gap G between the rod103and the barrel106.

As best seen inFIGS.15A,15B, the barrel cap110is an elongate hollow tube having a central lumen110L. In some examples, a proximal end110P is open and communicates with the lumen110L, and distal end110D is closed. InFIG.15A, the barrel cap110includes a male plug110X attached to an inner surface thereof which is configured to sealingly engage the female aspects of the lumen of the tip106T. InFIG.15B, the barrel cap110includes a female plug110X which is configured to sealingly engage the exterior wall of the tip106T.

FIGS.17A,17Bshow the device100fully assembled with the barrel seal104within the barrel106, the barrel106coaxially mounted over the rod103and received within the casing102, the tube seal108removably mounted on the tip106T, and the barrel cap110mounted over the tube seal108and a distal portion of the barrel106. InFIG.17Athe distal most part of the casing102overlaps the barrel cap110, whereas inFIG.17Bthe distal most portion of the cap overlaps the distal most part of the casing102.

FIG.6shows a fully assembled view and an exploded view of device100.

It should be noted that the device100does not utilize needles to transfer the plasma and buffy coat out of the fluid collection tube602and eliminates the need for using a separating gel.

FIG.16is an exploded view of an example device100which includes a casing102(FIGS.14A,14B) with its rod103, a barrel seal104(FIG.13), a barrel106(FIG.12), a tube seal108(FIGS.7A,7B) and a barrel cap110(FIGS.15A,15B).

FIGS.14A,14B: The casing102is an elongate hollow tube with a central lumen102L. In some examples, proximal end102P of the casing102is closed, and distal end102D is open and communicates with the central lumen102L. A rod103is partially housed within the central lumen102L. InFIG.14A, a distal end103D extends beyond the distal end102D of the casing102. InFIG.14B, the distal end102D of the casing extends beyond the distal end103D of the rod103. In some examples, the rod103is attached to the casing. For example, a proximal end103P of the rod103may be attached to the proximal end102P of the casing102. The diameter of the lumen102L is greater than the diameter of the rod103such that a gap G is formed between an external surface of the rod103and an interior wall of the casing102.

The rod103may be hollow or solid. The rod103serves to advance the barrel seal104(FIGS.13,16) from a proximal end106P of the barrel106towards the distal end106D of the barrel. The barrel seal104may be formed of an elastomeric material and fluidically seals the inner surface or lumen106L of the barrel106. In some examples, the barrel seal104abuts but is not attached to the rod103. In this example, once the rod103has advanced the seal104distally, retracting the rod103proximally will not retract the seal104. However, in other examples, the seal104may be attached to the rod103.

The rod103may have any shape and need not have a circular cross-section. The rod103must merely have sufficient structural integrity to advance the barrel seal104within the lumen106L.

Example PRP Extraction Using the Tube Seal with the Barrel (Two-Spin)

FIGS.18A-18Millustrate steps in a method using device100. Some of the steps are optional, and the order in which the steps are described are not limiting.

InFIG.18A, a fluid collection tube602containing whole blood which has been centrifuged to separate the whole blood into its constituent parts; namely, red blood cells, buffy coat and plasma.

InFIG.18B, the tube cap602C is removed from the fluid collection tube602, and the casing102with the rod103are removed from the fully-assembled device100.

InFIG.18C, the barrel cap110is removed, exposing the tube seal108and the distal end of the barrel106. The distal end106D of the barrel106with the tube seal108are inserted into the fluid collection tube602.

InFIG.18D(optional), the distal end of the barrel106is gently removed with a twisting motion leaving the tube seal108engaged with the lumen of the fluid collection tube602.

InFIG.18E(optional), the proximal end of barrel106is placed in abutment with the tube seal108and is used to push or advance the tube seal108within the fluid collection tube until the tube seal just contacts the plasma.

InFIG.18F(optional), the proximal end106P of the barrel106is withdrawn, the barrel106is flipped, and the distal end106D is placed in sealing engagement with the tube seal108.

InFIG.18G, as the barrel106and tube seal108are advanced distally into the fluid collection tube602, plasma will flow proximally (in the opposite direction) through lumen108L into the hollow interior106H of the barrel106. The barrel seal104is pushed proximally by the fluid flowing into the barrel106. The barrel106should be advanced until red blood cells just start to enter into the barrel. At that point, plasma and the whole buffy coat have been transferred to the barrel106. The conical shape of the distal end of the tube seal108will preferentially move the outer part of the buffy coat to the center of the tube seal108before red blood cells start to enter the tip106T.

InFIG.18H, the barrel106is withdrawn from the fluid collection tube602using a twisting and pulling motion to disengage the tube seal108from the barrel106. In other words, as the barrel106is withdrawn, the tube seal108remains in the fluid collection tube602with the remaining red blood cells. The barrel cap110is engaged with the distal end106D of the barrel106.

InFIGS.18I-1and18I-2, the barrel106containing the plasma and buffy coat (collectively PEP) is capped with device barrel cap110and centrifuged (second spin cycle) to separate the PEP into its constituent parts; namely, platelet poor plasma (PPP) on the top and platelet pallet (compacted platelets) proximate the barrel seal104. The centrifuged sample by volume comprises approximately 9/10 platelet poor plasma and 1/10 platelet pallet. One of ordinary skill in the art will appreciate that when inserting the tubular barrel into the centrifuge, the tip of the barrel should be pointing to the center axis of rotation.

InFIGS.18J-1and18J-2, a conventional syringe180is attached to the barrel106. More particularly, the male aspect of the syringe180interfaces with the female aspect of the barrel tip106T. In some examples, the rod103is inserted into the proximal end of the barrel106.

InFIGS.18K-1and18K-2, the distal end of the rod103is advanced distally within the barrel lumen106L toward the tip106T pushing the barrel seal104distally and expelling any residual air out of the barrel first (ideally), and then transferring ⅔-¾ of the platelets poor plasma (PPP) to the attached syringe180. One of ordinary skill in the art will appreciate that instead of (or in addition to) advancing the rod103, the plunger of the attached conventional syringe180may be retracted to affect the transfer of air and PPP. The conventional syringe180with air and the platelet poor plasma is disconnected from the barrel tip106T.

InFIGS.18L-1and18L-2, an empty conventional syringe180is attached to the Luer tip106T. The platelet pallet and remaining plasma are transferred back-and-forth between the barrel106and the syringe180by alternatingly pushing the rod103and the syringe plunger of the conventional syringe180. This back-and-forth transfer dislodges the platelet pallet and mixes it with remaining plasma thereby creating platelet rich plasma (PRP). See,FIG.18M. Now the whole PRP is transferred to the conventional syringe180and is ready for use.

Example PRP Extraction Using the Barrel with Ordinary Syringes (One-Spin)

FIGS.20A-20Millustrate an example process for creating PRP. In this example, the barrel106is the key feature, because it integrates the functions of both the fluid collection tube and the tube seal.

InFIG.20Athe fully assembled device100is disassembled by removing the barrel cap110, the tube seal108, case102and rod103from the barrel106, leaving the barrel seal104within the lumen of the tube106.

InFIGS.20B-1,20B-2and20B-3a conventional syringe180containing whole blood is attached to the barrel106, and the blood is transferred from the syringe180into the barrel106by advancing the plunger within the syringe. The barrel seal104is pushed toward the proximal end106P of the barrel106by the blood entering the tube106.

InFIGS.20C-1,20C-2, and20C-3the now empty conventional syringe108is disengaged from the barrel106(and discarded), and the barrel cap110is placed in sealing engagement with the tip106T of the barrel106.

InFIGS.20D-1and20D-2, the barrel106with the blood and the barrel cap110is centrifuged, separating the blood into a layer of red blood cells (RBC), buffy coat, and plasma.

InFIGS.20E-1and20E-2, the barrel cap110is removed from the barrel106, and a fresh (empty) conventional syringe180having a plunger movably mounted within is placed in engagement with the tip106T of the barrel106.

InFIGS.20F-1and20F-2the plasma and buffy coat (collectively “PEP”) are transferred from the barrel106into the syringe180. This may be accomplished either by (a) retracting the plunger within the syringe180; or (b) by advancing the rod103and the barrel seal104within the barrel106. Or both, as is the case with the tube. The red blood cells are not transferred from the barrel106into the syringe180.

InFIGS.20G-1and20G-2, the syringe180with the PEP are connected to a fresh barrel106.

InFIGS.20H-1and20H-2, the PEP is transferred from the syringe180into the barrel106, and barrel cap110is placed in sealing engagement with the barrel tip106T.

InFIGS.20I-1and20I-2, the capped barrel106containing the PEP is centrifuged (second spin cycle) to separate the PEP into its constituent parts; namely, platelet poor plasma (PPP) on the top and platelet pallet (compacted platelets) proximate the barrel seal104. The centrifuged sample by volume comprises approximately 9/10 platelet poor plasma and 1/10 platelet pallet.

InFIGS.20J-1and20J-2, a conventional syringe180is attached to the barrel106. More particularly, the male aspect of the syringe interfaces with the female aspect of the barrel tip106T. The rod103is inserted into the proximal end of the barrel106.

InFIGS.20K-1and20K-2, the distal end of the rod103is advanced distally within the barrel lumen106L toward the tip106T pushing the barrel seal104distally and expelling any residual air and ⅔-¾ of the platelets poor plasma (PPP) to the attached syringe180. One of ordinary skill in the art will appreciate that instead of (or in addition to) advancing the rod103, the plunger of the attached conventional syringe180may be retracted to affect the transfer of air and PPP. The conventional syringe180with air and the platelet poor plasma is disconnected from the barrel tip106T. One of ordinary skill in the art will appreciate that the residual air could be expelled from the barrel prior to connecting the syringe180.

InFIGS.20L-1and20L-2, an empty conventional syringe180is attached to the Luer tip106T. The platelet pallet and remaining plasma is transferred back-and-forth between the barrel106and the syringe180by alternatingly pushing the rod103and the syringe plunger of the conventional syringe180. This back-and-forth transfer is also applicable to the methods with the tube, that also use the barrel. This back-and-forth transfer dislodges platelet pallet and mixes it with remaining plasma thereby creating platelet rich plasma (PRP). See,FIG.20M. Now the whole PRP is transferred to the conventional syringe180and is ready for use.

Example PRP Extraction Using the Tube Seal with the Barrel (Single-Spin)

FIGS.19A-19I-2illustrate another example process for creating PRP.

InFIG.19A, a fluid collection tube containing a sample of whole blood is centrifuged to separate the blood into constituent layers of red blood cells (RBC), buffy coat, and plasma.

InFIG.19B, the casing102and rod103are removed from the barrel106, and the cap602C is removed from the fluid collection tube602.

InFIG.19C, the barrel cap110is removed from the barrel106, and the distal end of the barrel106with the barrel seal104inside the lumen of the barrel and the tube seal108mounted on the tip106T are inserted into the open mouth of a fluid collection tube602.

InFIG.19D(optional), the barrel is removed from the fluid collection tube with a gentle twisting motion to separate the tube seal108from the tip106T of the barrel106, leaving the tube seal108engaged with the inner surface of the fluid collection tube602.

InFIG.19E(optional), the barrel106is flipped and the proximal end106P is inserted into the fluid collection tube602and placed in abutment with the tube seal108. The barrel106is used to push the tube seal distally in the fluid collection tube until it comes in contact with the plasma. The proximal end of the barrel106is withdrawn, and the distal end of the barrel106is re-inserted into the sealing engagement with the fluid collection tube602.

InFIGS.19F-1and19F-2the barrel106is used to advance the tube seal108within the fluid collection tube602. As the barrel106is advanced distally into the fluid collection tube602, plasma enters into the barrel and pushes the barrel seal104proximally. The barrel106is advanced until between ⅔ and ¾ of the plasma has been transferred into the barrel106, leaving the red blood cells, buffy coat, and ¼ of the plasma. The barrel with the plasma is disengaged from the fluid collection tube602and discarded.

InFIGS.19G-1and19G-2, an empty barrel106is attached to the fluid collection tube602containing red blood cells, buffy coat, and remaining plasma. The barrel106is advanced into the fluid collection tube602until all of the plasma and the buffy coat are transferred into the barrel106, leaving the red blood cells.

InFIGS.19H-1and19H-2a fresh conventional syringe180is placed in sealing engagement with the tip106T of the barrel106containing the plasma and the buffy coat (collectively PRP).

InFIGS.19I-1and19I-2, the plasma and buffy coat (PRP) are transferred from the barrel into the syringe by either (a) retracting the plunger within the syringe180; or (b) by advancing the rod103and the barrel seal104within the barrel106. The barrel106is disconnected from the syringe and discarded, and a needle is attached to the syringe.

Example PRP Extraction Using the Tube Seal with the Syringe Connector200

FIG.21depicts an example of a syringe connector200which comprises an elongated tube having a lumen or through-hole200L extending between proximal and distal ends thereof. The connector200is formed of a transparent material which permits visualization of fluids within the through-hole200L. The proximal end is provided with a Luer-compatible female taper200P. A flange200F is provided proximate the distal end of connector200. Between the flange200F and the distal end of the connector200is a region200TS onto which the tube seal108is mounted. Flange200F limits the amount the tube seal108can be advanced along the distal end of the connector200. An outer diameter of the connector in the region200TS is sized to snugly (or sealingly) engage with the lumen or through-hole defined in the tube seal108. The distal end of connector200may in some examples also be provided with a Luer-compatible female taper200P.

FIG.22shows the tube seal mounted onto the region200TS of the connector200about to be inserted into a specimen holder602containing a blood specimen which has been centrifuged thereby separating the blood specimen into distinct layers of RBC, buffy coat and plasma.

FIG.23shows the connector ofFIG.22advanced into the collection tube602and the plasma transferred from the collection tube602into the through-hole200L thereby de-airing the through-hole200L. Fluid is transferred from the specimen holder to the syringe180as the syringe180and connector200are advanced into the collection tube along with tube seal108. The tube seal108seals the collection tube such that the displaced fluid is transferred into the syringe180.

FIG.24. shows the connector and collection tube ofFIG.23being coupled with syringe180.

FIG.25shows the connector and collection tube ofFIG.24coupled with syringe180after the plasma and buffy coat (platelet enriched plasma “PEP”) have been transferred from the collection tube602through connector200into the syringe180.

FIG.26shows the syringe180ofFIG.25after it has been disconnected from the connector200.

While the exemplary embodiments have been described in some detail, by way of example and for clarity of understanding, those of skill in the art will recognize that a variety of modification, adaptations, and changes may be employed. The scope of the present invention may be limited solely by the appending claims.