Patent Application
20240050695
The present invention relates to apparatus and methods for separating blood components. More particularly, the present invention relates to a foam collared float for effectively separating and removing specific components from blood.
Blood may be fractionated and the different fractions of the blood used for different medical needs. For instance, anemia (low erythrocyte levels) may be treated with infusions of erythrocytes. Thrombocytopenia (low thrombocyte (platelet) levels) may be treated with infusions of platelet concentrate.
The sedimentation of the various blood cells and plasma is based on the different specific gravity of the cells and the viscosity of the medium. When sedimented to equilibrium, the component with the highest specific gravity (density) eventually sediments to the bottom, and the lightest rises to the top. Under the influence of gravity or centrifugal force, blood spontaneously sediments into three layers. At equilibrium the top, low-density layer is a straw-colored clear fluid called plasma. Plasma is a water solution of salts, metabolites, peptides, and many proteins ranging from small (insulin) to very large (complement components). Plasma per se has limited use in medicine but may be further fractionated to yield proteins used, for instance, to treat hemophilia (factor VIII) or as a hemostatic agent (fibrinogen). The term platelet rich plasma (PRP) is used for this component because most of the plasma proteins and platelets in the whole blood are in the plasma following slow centrifugation so the concentration of platelets in the plasma has increased while suspended in supernatant plasma. The uppermost layer after centrifugation typically contains plasma proteins only and is typically called platelet-poor plasma (PPP) due to the absence or low number of platelets as a result of a “hard spin”.
The bottom, high-density layer is a deep red viscous fluid comprising a nuclear red blood cells (RBC) specialized for oxygen transport. The red color is imparted by a high concentration of chelated iron or heme that is responsible for the erythrocytes high specific gravity. Packed erythrocytes, matched for blood type, are useful for treatment of anemia caused by, e.g., bleeding. The relative volume of whole blood that consists of erythrocytes is called the hematocrit, and in normal human beings can range from about 38% to about 54%.
The intermediate layer is the smallest layer, appearing as a thin white band on top the erythrocyte layer and below the plasma, and is called the buffy coat. The buffy coat itself has two major components, nucleated leukocytes (white blood cells) and a nuclear smaller bodies called platelets (or thrombocytes). Leukocytes confer immunity and contribute to debris scavenging. Platelets seal ruptures in the blood vessels to stop bleeding and deliver growth and wound healing factors to the wound site. The buffy coat may be separated from whole blood when the blood is subjected to a “hard spin” in which the whole blood is spun hard enough and long enough so that platelets sediment from plasma onto packed red cells and white cells percolate up through red cell pack to the interface between red cells and plasma.
When whole blood is centrifuged at a low speed (e.g., up to 1,000 g) for a short time (e.g., two to four minutes) white cells sediment faster than red cells and both sediment much faster than platelets. At higher speeds the same distribution is obtained in a shorter time. The method of harvesting PRP from whole blood is based on this principle. Centrifugal sedimentation that takes the fractionation only as far as separation into packed erythrocytes and PRP is called a “soft spin” which is typically used to describe centrifugation conditions under which erythrocytes are sedimented but platelets remain in suspension. “Hard spin” is typically used to describe centrifugation conditions under which erythrocytes sediment and platelets sediment in a layer immediately above the layer of erythrocytes.
The auto-transfusion equipment used to make autologous platelet concentrates requires a skilled operator and considerable time and expense and these devices require a large prime volume of blood. While many of these devices have somewhat reduced the cost and the time required, skilled operators and time are still required. Accordingly, there remains a need for simple and effective methods and devices for separating and removing components from whole blood.
One variation may include a foam collared float which may have a wide float stem portion. As described herein, the foam is defined as a closed cell foam material in which the individual cells (or at least a majority of the individual cells) of the foam material are enclosed. A narrow float stem portion may be fixedly attached to the wide float stem portion. A float hole may have a first float hole end on the wide float stem portion and may have a second float hole end on the narrow float stem portion. A foam collar may be fixedly or detachably connected to the narrow float stem portion. In other variations, the foam collar may instead be positioned along the wide float stem portion while seated into secure placement within a circumferential groove defined around the float.
The wide float stem portion may have an upper float end located on a proximal end of the wide float stem portion. The narrow float stem portion may have a lower float end located on a distal end of the narrow float stem portion. The upper float end may be concave. The lower float end may be concave. The float hole may run through the center of the wide float stem portion and the center of the narrow float stem portion. The wide float stem portion may have a wide float stem portion diameter around 0.758 inches and may have a wide float stem portion length around 0.450 inches. The narrow float stem portion may have a narrow float stem portion diameter around 0.635 inches and may have a narrow float stem portion length around 0.250 inches.
The foam collar may have a foam collar inner dimension around 0.375 inches and may have a foam collar outer dimension around 0.625 inches. The foam collar may have an uncompressed density around 0.33 grams per cubic centimeter. The foam collar may have a fully compressed density between 0.95 and 1.20 grams per cubic centimeter.
One variation may include a foam collared float which may have a float stem. The float stem may have a float stem distal end and a float stem proximal end. The foam collared float may have a float hole. The float hole may have a first float hole end on the float stem distal end and may have a second float hole end on the float stem proximal end. The foam collared float may have a foam collar. The foam collar may be fixedly or detachably connected to the float stem.
The float stem distal end may be concave. The float stem proximal end may be concave. The float hole may run through the center of the float stem. The float stem may have a float stem diameter around 0.635 inches and may have a float stem length around 0.250 inches. The foam collar may have a foam collar inner dimension around 0.375 inches and may have a foam collar outer dimension around 0.625 inches. The foam collar may have an uncompressed density around 0.33 grams per cubic centimeter. The foam collar may have a fully compressed density between 0.95 and 1.20 grams per cubic centimeter.
In one variation, the float may generally comprise a first float stem portion having a first diameter, a second float stem portion fixedly attached to the wide float stem portion and having a second diameter which is less than the first diameter, a channel having a first opening on the first float stem portion and a second opening on the second float stem portion, and a compressible collar positioned about the second float stem portion and having a third diameter which is greater than the first diameter.
In another variation, the float may generally comprise a float stem including a float stem distal end and a float stem proximal end, a float channel having a first float opening on the float stem distal end and a second float opening on the float stem proximal end, and a compressible collar fixedly or detachably connected about the float stem.
In another variation, the float may generally comprise a first float stem portion having a first diameter, a second float stem portion fixedly attached to the wide float stem portion and having a second diameter which is less than the first diameter, a channel having a first opening on the first float stem portion and a second opening on the second float stem portion, and a compressible collar positioned about the second float stem portion and having a third diameter which is greater than the first diameter.
In another variation, the float may generally comprise a float stem including a float stem distal end and a float stem proximal end, a float channel having a first float opening on the float stem distal end and a second float opening on the float stem proximal end, and a compressible collar detachably connected about the float stem.
In another variation, a method of securing a float within a container may generally comprise positioning a float into a bottom of a container, introducing a volume of fluid within the bottom of the container such that the fluid covers the float, and forming a vapor lock between the float and the container such that a position of the float is secured relative to an interior of the container.
Throughout the description, terms such as “top”, “above, “bottom”, “below” are used to provide context with respect to the relative positioning of components when, e.g., a container tube with fractional components of blood are positioned when the longitudinal axis of a container tube is positioned upright or non-horizontally. Such description is used for illustrative purposes only.
As discussed herein, when sedimented to equilibrium, the component with the highest specific gravity (density) eventually sediments to the bottom, and the lightest rises to the top. Under the influence of gravity or centrifugal force, blood spontaneously sediments into three layers. At equilibrium the top, low-density layer is a straw-colored clear fluid called plasma. The term platelet-rich plasma (PRP) is used for this component because most of the plasma proteins and platelets in the whole blood are in the plasma following slow centrifugation so the concentration of platelets in the plasma has increased while suspended in supernatant plasma. The bottom, high-density layer comprises sedimented red blood cells (RBC). The intermediate layer, if the blood is subjected to further centrifugation, is called the buffy coat.
The present invention relates to apparatus and methods for rapid fractionation of blood into its different components, e.g., erythrocyte, plasma, and platelet or buffy coat fractions. The design described herein for a buffy coat concentrator should provide platelet and white blood cell (WBC) yields comparable to other gravitational platelet separation (GPS) designs. The manufacturing costs should be lower and the devices are easy to use. It also allows for the user to choose a desired level of buffy coat concentration. Markings on the tube can be provided to indicate the amount of platelet-depleted plasma (PPP) to be withdrawn prior to resuspension of the buffy coat to yield a desired concentration factor (the more PPP removed, the higher the concentration after resuspension in the remaining volume). Because platelets sediment onto a thin layer of red blood cells (RBC) trapped within the upper float concavity, platelet damage should be minimal and resuspension should be easier than when platelets are sedimented directly onto a hard surface.
One variation of the foam collar float 100 is shown in
While the cross-sectional shape of the first float stem portion 102 and the second float stem portion 104 may be uniform in shape, e.g., rounded or circular, both the first float stem portion 102 and the second float stem portion 104 may have shapes other than rounded, e.g., oval, square, rectangular, triangular, quad-angular, etc. Furthermore, while the shape of both the first float stem portion 102 and second float stem portion 104 may be uniform, e.g., both circular, they may be non-uniform as well where the first float stem portion 102 may have a first cross-sectional shape while the second float stem portion 104 may have a second cross-sectional shape different from the first cross-sectional shape.
A float channel 106 is defined and shown as running from an upper float portion 108 to a lower float portion 110 where the float channel 106 can extend from the center of the upper float portion 108 to a lower float portion 110. In other variations, the float channel 106 may be defined through the float 100 along locations other than the center of the upper float portion 108 and the center of the lower float portion 110. The upper float portion 108 may be defined as a surface which is shown as being concave in one variation. In other variations, the upper float portion 108 may be convex, flat, slanted, curved, or any combination thereof. The upper float portion 108 may be tapered to present a sloped conical shape or a sloped surface angled from one side of the upper float portion 108 towards the opposite side of the upper float portion 108. The lower float portion 110 is shown as being concave and having an angle relative to a longitudinal axis of the float collar 100. In other variations, the lower float portion 110 may be convex, flat, slanted, curved, or any combination thereof. The lower float portion 110 may be tapered to present a sloped conical shape or a sloped surface angled from one side of the lower float portion 110 towards the opposite side of the lower float portion 110. In any of these variations where the upper float portion 108 is concave, flattened, or convex, a layer may be applied to the upper float portion 108 which is relatively slippery. In one variation, a silicone layer may be formed upon the upper float portion 108 to facilitate the removal of platelets from the upper float portion 108.
While the lower float portion 110 may have any variation of surface, one advantage of a concave surface includes having white cells as well as platelets within a sample 122 positioned beneath the float 100 within a container 120 (as shown in
A float collar 112 is shown as detachably connected to or attached about the second float stem portion 104 such that the inner diameter of the float collar 112 may be sized to match the outer diameter of the second float stem portion 104 or may have an inner diameter which is slighter smaller than the outer diameter of the second float stem portion 104. The length of the float collar 112 may also be relatively less than the length of the second float stem portion 104 such that the second float stem portion 104 may extend past the float collar 112 when the float collar 112 is secured upon the second float stem portion 104. Other variations may include a float collar 112 having a length which is equivalent to the length of the second float stem portion 104 or a length which extends past that of the second float stem portion 104. In either case, with the inner diameter of the float collar 112 being less than the outer diameter of the first float stem portion 102, the float collar 112 may be positioned over the second float stem portion 104 to abut the shoulder defined where the distal end of the first float stem portion 102 is attached to the proximal end of the second float stem portion 104.
In other variations, the foam collar may instead be positioned along the wide float stem portion while seated into secure placement within a circumferential groove defined around the float.
While the float collar 112 may be comprised of a foam material, the float collar 112 may be comprised of a number of different compressible materials capable of performing the functions described herein and is not limited to foam materials. Examples of some materials suitable for fabricating a foam float collar may include, for instance, silicone (which is particularly compatible with platelets and has a high permeability to oxygen and nitrogen), polyethylene, fluoroelastomer (e.g., VITON, The Chemours Company, DE), or a number of other polymers having sufficient shape memory.
Furthermore, the outer diameter of the float collar 112 may extend past the outer diameter of the first float stem portion 102 so that the outer diameter of the float collar 112 may contact the inner diameter of the tube or container 120 within which float 100 is positioned, as shown in the side view of
As previously described, the float 100′ may be configured to incorporate a second float stem portion 130 which may be shaped into other structures.
The float 100′ with the collar 112 may be inserted into the interior of the container 120 such that the float 100′ forms an airtight seal between the float 100′ and the container interior, as illustrated in
In yet another variation, the float collar may be fabricated in another manner. One variation may include a float collar 140 formed as an O-ring where the float collar may be define a hollow interior 142 which may be filled with a gas (e.g., air, nitrogen, etc.) or liquid (e.g., water, saline, etc.). The float collar 140 may be formed of an elastomeric material, e.g., silicone, in various sizes for different float diameters.
Other variations of the float collar may include one having an elongated (e.g., elliptical, etc.) cross-sectional shape to increase the contact area between the float collar and the inner wall of the container. Another variation may include a rectangularly-shaped float collar 150 also defining a hollow interior 152, as shown in
The float collar itself may be configured in any one of several different variations depending upon the desired configuration of the float collar. In one variation, the float collar may be fabricated to have all of its exposed surfaces to be smooth (or skinned) where the exposed surfaces may be processed to present a smooth surface.
In cases where the foam collar is fabricated from a closed cell foam material, the outer surfaces of the fabricated foam collar may be relatively rough where sliced-open cells are exposed.
Another variation is shown in the top and bottom perspective views of
Another variation is shown in the top and bottom perspective views of
In any of these variations, only select surfaces may instead be roughened or smoothed depending upon the desired configuration. For instance, a float collar may be configured to present a smooth outer surface only while the other surfaces (inner, upper, and lower) may remain in a rough state. Such a float collar may be fabricated, e.g., by slicing a length of cord stock and punching a hole in the center in which case only the outer surface may be smooth.
The float may be configured in yet other variations as shown in the side and perspective views of
The float channel 226 extend between the upper float portion 228 and lower float portion 230 near or at the minimum height of the float 220 such that the float channel 226 may extend through both the first float stem portion 222 and the second float stem portion 224. With this configuration, the white blood cells may slide or move over the sloped lower float portion 230 to percolate up and through the float channel 226 to the upper float portion 228 as the red blood cells sediment below the lower float portion 230 during use. The buffy coat may form at the lower angled portion of the upper float portion 228.
This collection region 266, as shown in
One embodiment for securing the float 100 within a container, e.g., for manufacturing, handling, and/or shipment of the float 100 and container, may include simply positioning the float 100 within the empty container. Another variation may include placement of the float 100 within the container with an amount of a fluid such as anticoagulant introduced above the float 100 to create a locking or securement feature through the formation of a vapor lock.
While the fluid 302 introduced into the bottom of the container interior may be anticoagulant, other variations may instead use an isotonic saline as the fluid to form the vapor lock in order to secure a position of the float 100 at the bottom of the container. Any number of coagulants such as ACD-A anticoagulant (citrate) (Zimmer Biomet, IN) may be used where a small volume may be introduced into the container so that it can wick in and around the gap between the container interior wall and the float 100. The anticoagulant need not fill the entire gap from the bottom of the float to the top of the float so long as some amount of the liquid surrounds the entire circumference of the float 100 sufficient to create a liquid seal to prevent the dislodgment of the float 100 relative to the container. The sample to be processed may be simply introduced into the container with the anticoagulant already present for processing. A ratio of about 6 cc of ACD-A per 54 cc of blood may be sufficient to create a vapor lock although this ratio may be varied depending upon various factors, e.g., float size, container volume, sample volume, etc.
In yet another variation,
In each of these variations, the volume of fluid used to form the vapor lock for securing the float position may be enough to cover the float and prevent air from being reintroduced below the float after the float is initially pushed into the lower portion of the container. This vapor lock feature is shown in further detail in the side view of
The use of the vapor lock may be omitted entirely and the float channel 106 may instead be simply sealed or obstructed after the float 100 has been pushed into the container or tube during assembly. The volume of air beneath the float 100 may be urged or forced out of the container through the float channel 106 as the float 100 is pushed into the container. Once the float 100 has been desirably situation within the float, the float channel 106 may be obstructed or sealed to maintain the position of the float 100 within the container for shipment purposes. As the float 100 moves away from the floor of the container, the presence of the fluid and the movement of the float 100 may form a negative pressure beneath the float 100 and prevent its movement thereby locking its position within the container. Furthermore, the outer diameter of the float collar 112 when uncompressed may be slightly larger than the inner diameter of the container. As the float is inserted within the interior of the container, the float collar 112 may compress and provide a radial force against the interior walls of the container to further secure the float in position relative to container. Once the float 100 is desired to be removed from the container, the float channel 106 may be unsealed or unobstructed to allow for air or fluid to be introduced into the container and may further allow the float to move to its equilibrium position before, during, and/or after processing.
In yet another variation, rather than implementing a vapor lock with a fluid, the interior of the container may instead be placed under vacuum and sealed via a septum or other cover or cap with the float contained within. The float position within the container may be maintained due to the radial force imparted by the float collar against the interior walls of the container and prior to use. The negative pressure within the container may also help to distort or deflect the walls of the container inwardly (for non-glass containers) to further help maintain a position of the float within although the radial force provided by the float collar may be sufficient to maintain the position of the float without the use of the vacuum.
However, the vacuum may serve an additional purpose to generate a platelet-rich fibrin matrix (PRFM) which is PRP produced by processing freshly drawn blood without anticoagulant. When the needle of a blood-filled syringe (or connected via tubing to a patient's vein) punctures the septum sealing the top of the tube, the vacuum within the tube may immediately draw or suck the blood into the tube due to the pressure difference between the tube interior and the blood-filled syringe. The container filled with the drawn blood and the float within may then be spun immediately to separate the PRP from the red cells and the PRP (now located above the float) may be quickly withdrawn from the container and used before the blood has time to clot.
During shipment and handling, the float position within the container may be maintained, as described; however, even if the float may have migrated away from the floor of the container, the float will drop to the bottom of the container as blood is introduced into the container from above.
In yet another alternative, the container interior may include a volume of fluid such as the anticoagulant and may also be placed under vacuum. As the float position is maintained, as described, by the vapor lock and the vacuum, the float may remain in its initial position at or near the bottom of the container even with the introduction of blood. Furthermore, with the float collar under vacuum, the float collar (particularly if fabricated from foam) may expand further securing the float position within the container. The float may remain in its position at the bottom and the fluid or anticoagulant located below the float may not initially mix with the blood until the container is processed by spinning in which case the anticoagulant may then mix with the blood as the float moves from its initial position to its equilibrium position between the component layers of the blood.
With the introduction of the blood into the container, the float collar may reduce further back to its initial state with the removal of the negative pressure. Depending on the air permeability of the polymer material, e.g., foam, comprising the float collar, the air in the open space or voids within the foam may bleed out into the vacuum resulting in the float collar relaxing over time to its original state as the pressure inside the voids equilibrates with the lower pressure in the container. With the introduction of the blood into the container, the vacuum within the container will be lost while the voids may remain at a lower relative pressure. Depending upon the resiliency of the polymer itself to recovery of the expanded state, the float collar may no longer expand to effectively maintain the float in place against the container wall. Yet these effects may generally be ignored as the interference between the float collar and interior walls of the container are sufficient to maintain the position of the float.
Furthermore, as the float collar expands to lock the float in position after centrifugation, there is a reduced chance of red cells becoming trapped beneath the float from contaminating the PRP during vigorous resuspension. However, the tight fit of the float within the container, even without a float collar, is sufficient to reduce any such risks. The float collar ensures that the float remains at the bottom of the container during shipping and handling.
The float 100 is shown to have not risen to the top of the volume of fluid 602 because the centrifugally generated pressure on the foam collar 112 diminishes as the radius of rotation at which the float 100 is rotated decreases. At some point, the centrifugally generated pressure may become insufficient to compress the foam collar 112 enough to prevent it from adhering against the inner wall of the container. Hence, the overall density of the float assembly 100 is ideally such that the float 100 remains at the bottom of the container 604 when spinning with whole blood and begins rises as the higher density red blood cell begin to pack within the container 604 and push the float 100 upwards above the red blood cell pack.
With the foam collared float compressed against the inner wall of the container, the float may be maintained in position within the interior of the container. Despite movement of the container with the float positioned within, the float may maintain its relative position along the interior wall of the container. For instance, even with the assembly shown being struck multiple times against a surface, the position of the float within remains securely positioned along the wall of the container. Under centrifugation, the walls of the container may bulge or widen slightly allowing for the foam collared float 100 to rise to an equilibrium position with the bulk of RBC packing out beneath the foam collared float 100 and plasma above the foam collared float 100. Hence the foam collar float 100 may be configured to have its density tuned to automatically position itself between the two layers under centrifugation. For example, the foam collar float 100 may have a density which is tuned specifically for use with whole blood, e.g., 1000 to 1100 kg/m 3 (or specific density of 1.0 to 1.1 grams per cubic centimeter at 25° C.), while in other variations, the foam collar float 100 may be fabricated to have a different density, e.g., 1.03 to 1.07 grams per cubic centimeter, etc.
The apparatus and methods disclosed above are not limited to the individual embodiments which are shown or described but may include combinations which incorporate individual features between the different variations. Modification of the above-described assemblies and methods for carrying out the invention, combinations between different variations as practicable, and variations of aspects of the invention that are obvious to those of skill in the art are intended to be within the scope of the claims.
This application claims the benefit of priority to U.S. Prov. 63/371,483 filed Aug. 15, 2022, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63371483 | Aug 2022 | US |
