US20230338628A1 - System and method for isolating alpha 2m molecules - Google Patents
System and method for isolating alpha 2m molecules Download PDFInfo
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- US20230338628A1 US20230338628A1 US18/215,498 US202318215498A US2023338628A1 US 20230338628 A1 US20230338628 A1 US 20230338628A1 US 202318215498 A US202318215498 A US 202318215498A US 2023338628 A1 US2023338628 A1 US 2023338628A1
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- 102100033312 Alpha-2-macroglobulin Human genes 0.000 title claims description 91
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Definitions
- the present disclosure relates to medical procedures for the isolation and delivery of Alpha-2 Macroglobulin ( ⁇ 2M) molecules from a patient's own blood plasma to treat musculoskeletal conditions.
- ⁇ 2M Alpha-2 Macroglobulin
- PRP and PPP therapies have become accepted forms of treatment for various musculoskeletal conditions.
- components of a patient's own blood are isolated and then injected into affected areas of the patient's body to accelerate the healing of injured musculoskeletal components such as tendons, ligaments, muscles and joints.
- blood components e.g., Alpha-2 Macroglobulin molecules
- PRP and PPP therapies make use of a patient's own healing system to address musculoskeletal conditions.
- the treatment of joints includes the injection of Alpha-2 Macroglobulin ( ⁇ 2M) molecules isolated from the plasma of the patient's own blood. More specifically, the injection of ⁇ 2M molecules into a patient's joint may be employed to slow the progression of a degenerative joint disease (e.g., osteoarthritis) by preventing (or at least arresting) the breakdown and loss of cartilage therein.
- a degenerative joint disease e.g., osteoarthritis
- a method for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for
- a kit for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included.
- each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe
- the kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the ⁇ 2M molecules from other components of the plasma within the at least one isolator.
- a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centr
- FIG. 1 is an overview block diagram of aspects of an example system and method of isolating ⁇ 2M from whole blood in preparation for delivery by injection.
- FIGS. 2 a , 2 b , 2 c , 2 d , 2 e , 2 f , 2 g , 2 h , 2 i and 2 j together, provide a more detailed presentation of aspects of the example system and method of FIG. 1 .
- FIG. 3 provides a flow chart of the method of FIG. 1 .
- ⁇ 2M molecule isolation system implementing a method for isolating of ⁇ 2M molecules from whole blood of a patient in preparation for use in treating a musculoskeletal condition of that patient.
- a method for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for
- a kit for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included.
- each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe
- the kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the ⁇ 2M molecules from other components of the plasma within the at least one isolator.
- a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centr
- an ⁇ 2M molecule isolation system 1000 may include one or more of a whole blood syringe 200 , a set of multiple separator tubes 300 , a transfer device 400 , a centrifuge 500 , a transfer syringe 600 , one or more isolators 700 , and/or an injectate syringe 800 .
- the system 1000 may be implemented as a kit that is made up of a relatively small number of relatively small and lightweight components that are able to be more feasibly transported within a vehicle used by medical personnel (e.g., a doctor, veterinarian, medical technician, nurse, etc.).
- the system 1000 enables the isolation of ⁇ 2M molecules for injection into a joint or other musculoskeletal structure in less time than is possible in the prior art.
- the one or more isolators 700 depicted and discussed in the present application were each earlier referred to as a “centrifugal concentrator” in the aforementioned U.S. Provisional Application 63/209,685 filed Jun. 11, 2021, the disclosure of which is incorporated herein by reference for all purposes.
- the isolation of ⁇ 2M molecules for use in treating a musculoskeletal condition begins with use of the whole blood syringe 200 to draw an amount of whole blood from the patient to be treated (regardless of whether the patient is a human being or other form of animal), and then convey portions of that blood into each of multiple separator tubes 300 .
- the set of separator tubes 300 may then be placed within the centrifuge 500 to be subjected to centrifugal force for a first predetermined period of time (i.e., a first stage of centrifuging) to cause separation of the blood plasma containing the ⁇ 2M molecules from other components of the whole blood with the aid of a separator gel incorporated into each of the separator tubes 300 .
- one or both of a transfer device 400 and a transfer syringe 600 may then be used to retrieve the separated blood plasma from each of the separator tubes 300 , and transfer that plasma to one or more isolators 700 .
- the one or more isolators 700 may then be placed within the centrifuge 500 to be subjected to centrifugal force for a second predetermined period of time (i.e., a second stage of centrifuging) to cause isolation of the ⁇ 2M molecules from the plasma with the aid of a membrane filter incorporated into each isolator 700 .
- the injectate syringe 800 may then be used to retrieve the ⁇ 2M molecules from the one or more isolators 700 in preparation for injecting the now isolated ⁇ 2M molecules into a joint or other musculoskeletal structure of the patient.
- the set of separator tubes 300 may be either a set of non-vacuum separator tubes 300 a or a set of vacuum separator tubes 300 b .
- Each of the different types of separator tube 300 a and 300 b may be an elongate transparent tube with a single opening on one end that is sealed with a cap 310 to at least maintain sterile conditions therein.
- the cap 310 may be formed from a relatively flexible material that enables a hollow needle to penetrate therethrough for transferring gases and/or fluids into and/or out of the interior of each of the separator tubes 300 a or 300 b in a manner in which a seal is maintained around such a needle.
- Such a flexible material may also be self-sealing in a manner that causes a re-sealing of holes formed therethrough by the penetration and subsequent removal of such a needle.
- each of the vacuum separator tubes 300 b may be a VACUTAINER® tube of a type offered by Becton, Dickson and Company of Franklin Lakes, New Jersey, USA.
- each such vacuum separator tube 300 b in its new and unused condition, may be pre-provided with a vacuum therein that the seal provided by the cap 310 is used to maintain.
- the quantity of separator tubes 300 a or 300 b that are used may vary based on such factors as the volume of whole blood 110 that may be safely drawn from the patient, the type and/or severity of the musculoskeletal condition that is to be treated, and/or the maximum quantity of separator tubes 300 a or 300 b that may be used with the centrifuge 500 at a time.
- the system 1000 may be offered in differently-sized variants of kits, such as a smaller variant of kit that may include 1 to 4 separator tubes 300 a or 300 b , a mid-sized variant of kit that may include 5 to 8 separator tubes 300 a or 300 b , and/or a larger variant of kit that may include 9 to 16 (or still more) separator tubes 300 a or 300 b.
- a plunger 220 of the whole blood syringe 200 may be operated to draw whole blood 110 from a blood vessel of a patient (whether a human being or other form of animal) and into the whole blood syringe 200 via a needle 211 thereof.
- the whole blood syringe 200 may include a human-readable scale by which the volume of whole blood that is drawn is able to be measured as the plunger 220 is so operated to ensure that just the amount of whole blood 110 that is needed for the chosen quantity of separator tubes 300 a or 300 b is successfully drawn.
- the whole blood syringe 200 may then be used to inject a portion of the drawn whole blood into each of the separator tubes 300 a or 300 b through the cap 310 via the needle 211 .
- the whole blood syringe 200 may be partially pre-filled (e.g., by the nurse, medical technician, veterinarian technician, doctor, veterinarian, etc.) with an amount of an anticoagulant 250 , such as a citrate dextrose solution (ACD-A), to prevent the drawn whole blood from coagulating therein.
- an anticoagulant 250 such as a citrate dextrose solution (ACD-A)
- each of the different types of separator tube 300 a and 300 b may include (at least in its new and unused condition) a small amount of a separator gel 350 disposed toward the end opposite the end that is closed with the cap 310 .
- a separator gel 350 disposed toward the end opposite the end that is closed with the cap 310 .
- the set of separator tubes 300 a or 300 b may be placed within the centrifuge 500 to be subjected to centrifugal force for a first period of time that is deemed sufficient to fully separate the plasma 113 thereof from the red and white blood cells 111 thereof. More specifically, and as depicted, the centrifuge 500 may be used in conjunction with the separator gel 350 to effect such a separation of components of the whole blood 110 .
- the separator gel 350 within each of the separator tubes 300 a or 300 b should occupy a position that physically separates the plasma 113 from the red and white blood cells 111 , thereby preventing these blood components 111 and 113 from becoming mixed together, again.
- the centrifuge 500 may include a rotor 553 that defines a set of holding positions 530 that each have a shape and dimensions selected to hold a tube of matching shape and dimensions, such as one of the separator tubes 300 a or 300 b .
- the quantity and placement of such holding positions 530 may be selected to enable various quantities of such tubes to be distributed among the holding positions 530 in a manner that distributes the weight thereof in a balanced manner that enables relatively smooth operation of the centrifuge 500 .
- the depicted rotor 553 is exchangeable within one or more other rotors to thereby enable the centrifuge to reconfigured to work with various different quantities and/or combinations of various tubes and/or other varieties of containers of differing shapes and/or sizes.
- the centrifuge 500 is fitted with (or otherwise includes) a rotor with 2 or more “buckets.” Each such bucket may be able to be fitted with any of a variety of differing types of holder that may each be designed to provide holding position(s) for a differing quantity of and/or combination of various tubes and/or other varieties of containers of differing shapes and/or sizes.
- the transfer device 400 may be a dual-flow device 400 a .
- the transfer device 400 may be a three-way valve 400 b.
- Each of the different types of transfer device 400 a and 400 b may incorporate the depicted combination of a connected a separator tube port 430 , a syringe port 460 , and a filtered air port 490 .
- each of the different types of transfer device 400 a and 400 b is configured to configured to enable external air 990 surrounding the transfer device 400 a or 400 b to be drawn in through the air filter 450 at the filtered air port 490 and conveyed to a separator tube 300 a or 300 b coupled to the separator tube port 430 as part enabling plasma 113 to be transferred from the separator tube 300 a or 300 b to the transfer syringe 600 coupled to the syringe port 460 .
- the interior volume of the transfer syringe 600 is sufficiently large that all of the sum total of the amounts of the plasma 113 isolated within all of the separator tubes 300 a or 300 b (as a result of being subjected to centrifugal force by the centrifuge 500 ) is able to be combined and retained within the transfer syringe 600 .
- the transfer syringe 600 is to remain connected to the syringe port 460 by its end connector 610 throughout the time that the plasma 113 is being transferred from each of the vacuum containers 100 , and into the transfer syringe 600 .
- FIG. 2 D depicts aspects of the manner in which the dual-flow device 400 a enables a simultaneous transfer of filtered air 994 into a separator container 300 a or 300 b , and of plasma 113 out of the separator container 300 a or 300 b as part of transferring plasma 994 to the transfer syringe 600 .
- the separator tube port 430 may incorporate both an air needle 439 and a plasma needle 431 that are each positioned to penetrate through the cap 310 of a separator tube 300 a or 300 b to enable the flow through each of gases and/or liquids into and/or out of such a separator tube 300 a or 300 b .
- the syringe port 460 may be configured to form a connection with an end connector 610 carried at one end of the transfer syringe 600 .
- Pulling the plunger 660 of the transfer syringe 600 away from the end connector 610 thereof may then draw plasma 994 from within the separator tube 300 a or 300 b , and into the transfer syringe 660 , via the plasma needle 431 and the end connector 610 .
- more filtered air 994 may be drawn into the separator tube 300 a or 300 b to replace the plasma 994 that is so drawn out.
- FIG. 2 E depicts aspects of the manner in which the three-way valve 400 b enables a selective transfer of filtered air 994 into a separator container 300 a or 300 b , and of plasma 113 out of the separator container 300 a or 300 b as part of transferring plasma 994 to the transfer syringe 600 .
- the separator tube port 430 of the three-way valve 400 b may incorporate just a single needle 431 that is positioned to penetrate through the cap 310 of a separator tube 300 a or 300 b to enable the flow therethrough of gases and/or liquids into and/or out of such a separator tube 300 a or 300 b .
- the syringe port 460 may be configured to form a connection with an end connector 610 carried at one end of the transfer syringe 600 .
- the three-way valve 400 b may incorporate a manually-operable valve (not specifically shown) of a type that is operable between at least two positions, where each position of the at least two positions causes one of the three ports 430 , 460 or 490 to be closed off from the other two of these two ports, while allowing gases and/or liquids to flow freely between the other two.
- a manually-operable valve (not specifically shown) of a type that is operable between at least two positions, where each position of the at least two positions causes one of the three ports 430 , 460 or 490 to be closed off from the other two of these two ports, while allowing gases and/or liquids to flow freely between the other two.
- the transfer of plasma 113 therefrom, and into the transfer syringe 600 may begin with the three-way valve 400 b being operated to close off the separator tube port 430 , thereby connecting the syringe port 460 to the filtered air port 490 .
- the plunger 660 of the transfer syringe 600 may be operated to draw filtered air 994 into the transfer syringe 600 .
- the plunger 660 of the transfer syringe 600 may be operated to cause external air 990 that surrounds the three-way valve 400 b to be drawn in through the air filter 450 , thereby being filtered to become the filtered air 994 that is drawn into the transfer syringe 600 .
- the three-way valve 400 b may then operated to close off the filtered air port 490 , thereby connecting the syringe port 460 to the separator tube port 430 .
- the plunger 660 of the transfer syringe 600 may be operated to send filtered air 994 out of the transfer syringe 600 , through the three-way valve 400 b , through the single needle 431 , and into the separator tube 300 a or 300 b that is coupled to the separator tube port 430 .
- the plunger 660 of the transfer syringe 600 may then be operated to draw most, if not all, of the plasma 113 out of the separator tube 300 a or 300 b , through the single needle 431 , through the three-way valve 400 b , and into transfer syringe 600 .
- the transfer syringe 600 may then be disconnected from the transfer device 400 a or 400 b . Then, a needle 611 may be connected to the end connector 610 of the transfer syringe 600 in preparation for injecting the plasma 113 into the isolator 700 .
- the isolator 700 may include a combination of a first cylinder 701 and a second cylinder 702 . Both of these cylinders 701 and 702 may be of a generally elongate shape defining a pair of ends.
- first cylinder 701 may be sealed (or sealable) with a septum cap 710 that may provide a self-sealing aperture through which a needle or other form of tube of relatively small diameter tube may be inserted to effect the transfer of gases and/or liquids into and/or out of the interior volume of the first cylinder 701 .
- the other end of the first cylinder 701 may incorporate a membrane filter 750 .
- the membrane filter 750 may have a filter diameter ranging from 100 kD to 500 kD.
- the second cylinder 702 may be configured to make the isolator 700 more amenable for use with the centrifuge 700 . More specifically, one end of the second cylinder 702 may be closed off with a conical end to ease insertion into the centrifuge 500 , while the other end may be open to enable the two cylinders 701 and 702 to be assembled by inserting part of the end of the first cylinder 701 that includes the membrane filter 750 therein.
- the isolator 700 may be of an extended length variation 700 a in which the volume of the first cylinder 701 is increased by sealing the end opposite the membrane filter 750 with an extended variant of the septum cap 710 that provides a cylindrical extension to the cylindrical wall of the first cylinder 701 to increase the length of the first cylinder 701 .
- the isolator 700 may be of a standard length variation 700 b in which the volume of the first cylinder 701 is not so increased. More precisely, instead of sealing the end opposite the membrane filter 750 with the extended variant of the septum cap 710 , a standard variant of the septum cap 710 is used that does not provide the cylindrical extension.
- the needle 611 may then be inserted through the aperture of the septum cap 710 .
- the plunger 660 of the transfer syringe 600 may then be operated to transfer the plasma 113 out of the transfer syringe 600 , and into the first cylinder 701 through the needle 611 and the aperture of the septum cap 710 .
- the still assembled isolator 700 may be placed within the centrifuge 500 to be subjected to centrifugal force for a second period of time that is deemed sufficient to fully separate the ⁇ 2M molecules 117 from the rest of the plasma 113 originally transferred into the first cylinder 701 . More specifically, and as depicted, the centrifuge 500 may be used in conjunction with the membrane filter 750 to effect such a separation of components of the plasma 113 .
- the ⁇ 2M molecules 117 should remain within the first cylinder 701 , while the other components of the plasma 114 should be retained within the second cylinder 702 as the depicted waste plasma 114 .
- the centrifuge 500 may include a rotor 557 that defines a pair of holding positions 570 that each have a shape and dimensions selected to hold a tube of matching shape and dimensions, such as the isolator 700 .
- the pair of such holding positions 570 as defined by the rotor 557 , may be positioned to enable the placement of a pair of the isolators 700 at locations that distribute the weight thereof in a balanced manner that enables relatively smooth operation of the centrifuge 500 .
- a range of variants may also include differing quantities of isolators 700 . More specifically, and by way of example, it may be that the aforedescribed smaller and mid-sized variants include a single isolator 700 , while the larger variant includes two of the isolators 700 .
- a dummy weight of a shape and size similar to the isolator 700 may be included to provide a counterbalance to the weight of the isolator 700 with plasma 113 therein to enable balancing of the centrifuge 500 .
- all of the aforedescribed size variants of the system 1000 may be provided with a pair of isolators 700 . It may be that, for the aforedescribed smaller and mid-sized variants, the second one of the two isolators 700 is to be filled with water to serve the purpose of being the counterbalance.
- the depicted rotor 553 is exchangeable within one or more other rotors to thereby enable the centrifuge to reconfigured to work with various different quantities and/or combinations of various tubes and/or other varieties of containers of differing shapes and/or sizes.
- the centrifuge 500 is fitted with (or otherwise includes) a rotor with 2 or more “buckets.” Each such bucket may be able to be fitted with any of a variety of differing types of holder that may each be designed to provide holding position(s) for a differing quantity of and/or combination of various tubes and/or other varieties of containers of differing shapes and/or sizes.
- centrifuge 500 is also a far simpler, more durable and far less expensive piece of equipment than a peristaltic pump such that equipping a vehicle used to make house calls with the centrifuge 500 is far more feasible.
- a needle 811 connected to an end connector 810 of an injectate syringe 800 may be inserted through the aperture of the septum cap 710 .
- a plunger 880 of the injectate syringe 800 may then be operated to transfer the ⁇ 2M molecules 117 from the first cylinder 701 , and into the injectate syringe 800 .
- isolator 700 is used to isolate the ⁇ 2M molecules 117 of a particular patient, such operations may be repeated to transfer the ⁇ 2M molecules 117 out of each such isolator 700 .
- the injectate syringe 800 may then be used directly to inject the ⁇ 2M molecules 117 into a joint or other musculoskeletal structure of the patient.
- the injectate syringe 800 may be used to transfer the ⁇ 2M molecules 117 into one or more other syringes (not shown) that may then be used to inject the ⁇ 2M molecules 117 into a joint or other musculoskeletal structure of the patient.
- the injectate syringe 800 may be used to transfer the ⁇ 2M molecules 117 into storage vials or still other container(s) (not shown) for temporary storage in preparation for the ⁇ 2M molecules 117 to be so injected into a joint or other musculoskeletal structure of the patient at a later time.
- FIG. 3 is a flowchart 2100 depicting aspects of the operation of an ⁇ 2M molecule isolation system to perform a method of isolating ⁇ 2M molecules from a patient's whole blood for use in treating a musculoskeletal condition of that patient.
- whole blood may be drawn from a patient (e.g., a human being or other form of animal) who/that may be suffering from a musculoskeletal condition affecting a joint or other musculoskeletal structure.
- a syringe inserted into an artery or vein of the patient may be used (e.g., the whole blood syringe 200 of the system 1000 ).
- the whole blood may be transferred to one or more separator tubes that may each be preloaded with a separator gel (e.g., one or more of the separator tubes 300 a or 300 b that are each preloaded with an amount of the separator gel 350 ).
- a separator gel e.g., one or more of the separator tubes 300 a or 300 b that are each preloaded with an amount of the separator gel 350 .
- the quantity of separator tubes may vary. Again, there may be more than one variant of the system that may be differentiated by the quantity of separator tubes that it may include.
- the separator tube(s) may be placed within a centrifuge (e.g., the centrifuge 500 ), and the centrifuge may be operated to exert centrifugal force on the separator tube(s) in a first stage of centrifuging.
- a combination of the exerted centrifugal force and the separator gel within each separator tube may be used to separate the plasma of the whole blood from at least the red and white blood cells of the whole blood.
- At 2130 at least a transfer syringe (e.g., the transfer syringe 600 ) may be used to retrieve the plasma from within the separator tube(s), and to transfer the plasma into at least one isolator incorporating a filter (e.g., at least one of the isolator 700 incorporating the filter 750 ).
- a transfer syringe e.g., the transfer syringe 600
- the transfer syringe 600 may be used to retrieve the plasma from within the separator tube(s), and to transfer the plasma into at least one isolator incorporating a filter (e.g., at least one of the isolator 700 incorporating the filter 750 ).
- the quantity of separator tubes may vary across multiple variations of the system, it may be that the quantity of isolators also varies in a manner that is at least partially correlated to the quantity of separator tubes.
- a pair of isolators is regularly included with the expectation that, where they are not both used, the unused one may be filled with an amount of water or other substance to serve as a counterbalance to the one that is used during a second stage of centrifuging.
- the isolator(s) may be placed within the centrifuge, and the centrifuge may be operated to exert centrifugal force on the isolator(s) in the aforementioned second stage of centrifuging.
- a combination of the exerted centrifugal force and the filter within each isolator that is filled with plasma may be used to isolate the ⁇ 2M molecules from other components of the plasma.
- a counterbalancing weight, or other isolator that is filled with water or another substance to serve as a counterbalancing weight may be required to balance the centrifuge.
- an injectate syringe (e.g., the injectate syringe 800 ) may be used to retrieve the ⁇ 2M molecules from within the isolator(s).
- the patient may then be treated with the ⁇ 2M molecules, either with injection(s) directly from the injectate syringe, or from other syringe(s) to which the ⁇ 2M molecules may be transferred from the injectate syringe.
- the ⁇ 2M molecules may be stored for later use in such treatment.
- a method for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for
- the method may further include: retrieving at least a portion of the ⁇ 2M molecules from within the at least one isolator; and injecting at least the portion of the ⁇ 2M molecules into a musculoskeletal structure of a patient from which the whole blood was drawn.
- Each separator tube of the at least one separator tube may include an elongate transparent tube that defines an opening at one end that is sealed with a cap, and the cap may be formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn.
- Depositing the whole blood into at least one separator tube may include: inserting a needle of the syringe through the cap of each separator tube of the at least one separator tube; and injecting at least a portion of the whole blood into each separator tube of the at least one separator tube from within the syringe.
- Each separator tube of the at least one separator tube may include either a non-vacuum separator tube, or a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
- the method may further include: using the syringe to draw the whole blood from a patient into which the ⁇ 2M molecules are to be injected; and partially pre-filling the syringe with an anticoagulant before using the syringe to draw the whole blood from the patient.
- the first holder may include either a first removable holder configured to be inserted into a bucket of the centrifuge, or a first exchangeable rotor of the centrifuge; and the second holder may include either a second removable holder configured to be inserted into a bucket of the centrifuge, or a second exchangeable rotor of the centrifuge.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may include: using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; and using the transfer syringe to deposit the one or more portions of the plasma into the at least one isolator.
- the at least one separator tube, the centrifuge, the transfer syringe and the at least one isolator, together, may form a kit for isolating the ⁇ 2M molecules from the whole blood; and multiple versions of the kit may be defined by at least one of a quantity of separator tubes included in the at least one separator tube and a quantity of isolators included in the at least one isolator.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include: coupling the transfer syringe to a syringe port of a transfer device; coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the transfer device, wherein the separator tube port comprises at least one hollow needle configured to simultaneously couple the separator tube port to the syringe port and to a filtered air port of the transfer device; and while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least one portion of the one or more portions of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through an air filter at the filtered air port and into the separator tube through the transfer device.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include coupling the transfer syringe to a syringe port of a three-way valve, coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the three-way valve, and while each separator tube of the at least one separator tube is coupled to the separator tube port, performing operations including: with the three-way valve operated to couple a filtered air port of the three-way valve to the syringe port, operating a plunger of the transfer syringe to draw air through an air filter at the filtered air port, through the three-way valve, and into the transfer syringe; and with the three-way valve operated to couple the separator tube port to the syringe port, operating the plunger of the transfer syringe to inject the filtered air into the separator tube through the three-way valve, and to withdraw at least one
- Each isolator of the at least one isolator may include a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; a first end of the first cylindrical wall of the first cylinder may define an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder may be closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap may be formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include: using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; inserting a needle of the transfer syringe through the septum cap of each isolator of the at least one isolator; and injecting the one or more portions of the plasma into the first interior space from within the transfer syringe.
- Isolating the ⁇ 2M molecules from other components of the plasma within the at least one isolator may include isolating the ⁇ 2M molecules from other components within the first interior space of each isolator of the at least one isolator from the other components of the plasma within the second interior space of each isolator of the at least one isolator.
- the septum cap may further include a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
- a kit for isolating Alpha-2 Macroglobulin ( ⁇ 2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included.
- each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe
- the kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the ⁇ 2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the ⁇ 2M molecules from other components of the plasma within the at least one isolator.
- a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centr
- Each separator tube of the at least one separator tube may include either a non-vacuum separator tube, or a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
- the centrifuge may further include at least one exchangeable rotor to enable the centrifuge to be used in the first centrifuging stage and the second centrifuging stage by exchanging the at least one exchangeable rotor.
- the centrifuge may further include a rotor that is configured to define multiple buckets into which exchangeable holders of differing configurations may be installed to enable the centrifuge to be used in the first centrifuging stage and the second centrifuging stage by exchanging holders within the multiple buckets.
- the kit may further include a transfer device, wherein: the transfer device may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port; and while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe may be able to be operated to withdraw at least a portion of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through the air filter at the filtered air port and into the separator tube through the transfer device.
- the transfer device may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port; and while each separator tube of
- the kit may further include a three-way valve, wherein: the three-way valve may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port.
- the three-way valve may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port.
- each separator tube of the at least one separator tube is coupled to the separator tube port
- the three-way valve and a plunger of the transfer syringe may be able to be operated to perform operations including: with the three-way valve operated to couple a filtered air port of the three-way valve to the syringe port, the plunger of the transfer syringe is able to be operated to draw air through the air filter at the filtered air port, through the three-way valve, and into the transfer syringe; and with the three-way valve operated to couple the separator tube port to the syringe port, the plunger of the transfer syringe is able to be operated to inject the filtered air into the separator tube through the three-way valve, and to withdraw at least a portion of the plasma from the separator tube and into the transfer syringe through the three-way valve.
- the septum cap may further include a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
Abstract
A method includes: depositing whole blood into at least one separator tube; subjecting the at least one separator tube to a first centrifugal force to cause a combination of the first centrifugal force and separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood from red and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes α2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator; and subjecting the at least one isolator to a second centrifugal force to cause a combination of the second centrifugal force and a filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.
Description
- This application is a divisional of U.S. patent application Ser. No. 17/837,090 entitled “SYSTEM AND METHOD FOR ISOLATING α2M MOLECULES” filed Jun. 10, 2022; which claims the benefit of the priority date of U.S. Provisional Application 63/209,685 entitled “SYSTEM AND METHOD FOR ISOLATING α2M MOLECULES” filed Jun. 11, 2021; the disclosures of each of which is incorporated herein by reference for all purposes.
- The present disclosure relates to medical procedures for the isolation and delivery of Alpha-2 Macroglobulin (α2M) molecules from a patient's own blood plasma to treat musculoskeletal conditions.
- Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) therapies have become accepted forms of treatment for various musculoskeletal conditions. In PRP and PPP therapies, components of a patient's own blood are isolated and then injected into affected areas of the patient's body to accelerate the healing of injured musculoskeletal components such as tendons, ligaments, muscles and joints. As will be familiar to those skilled in the art, such therapies require the use of blood components (e.g., Alpha-2 Macroglobulin molecules) from the blood of the specific patient that is being treated such that those blood components are said to represent autologous ortho-biologics. Thus, PRP and PPP therapies make use of a patient's own healing system to address musculoskeletal conditions.
- In one form of both PRP and PPP therapies, the treatment of joints includes the injection of Alpha-2 Macroglobulin (α2M) molecules isolated from the plasma of the patient's own blood. More specifically, the injection of α2M molecules into a patient's joint may be employed to slow the progression of a degenerative joint disease (e.g., osteoarthritis) by preventing (or at least arresting) the breakdown and loss of cartilage therein.
- Unfortunately, the isolation of α2M molecules for such an injection is a laborious and time-consuming process requiring specialized expensive equipment that is normally available only in a laboratory. Among such specialized expensive equipment is a peristaltic pump. While hospitals and/or other relatively large medical facilities may have such equipment and available personnel to carry out such an isolation process, smaller medical facilities (e.g., the doctor offices often located in rural areas) often do not.
- Additionally, even where such a smaller medical facility is able to acquire such specialized expensive equipment and/or has the necessary personnel available for such a laborious and time-consuming process, there may be situations in which bringing a patient to such a medical facility may be prohibitively difficult, if not impossible, thereby necessitating making house calls. Such situations may arise, for example, in the case of human patients with severe limitations in their mobility. Such situations may also arise, for example, in the case of equine patients and/or other large four-legged animal patients that may be at least difficult to transport.
- The need to make house calls as part of treating patients with α2M molecules can result in considerable delays in the commencement of treatment due to the need to draw blood and then inject α2M molecules in separate visits, as a result of needing to bring the drawn blood back to the medical facility where such specialized expensive equipment is maintained. An effort could be made to reduce such delays by bringing such specialized expensive equipment to patient locations as part of making house calls, but this can result in damage to such equipment and/or in causing such equipment to become less available for use in helping other patients by not leaving it in place at a medical facility. Further, the performance of the laborious and time-consuming process of isolating α2M molecules during a house call can make the duration of a house call prohibitively long.
- A need exists for a less time-consuming and cumbersome approach to isolating α2M molecules during a house call.
- Technologies are described for more efficiently isolating α2M molecules in a non-laboratory setting for use in treating musculoskeletal conditions.
- A method for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.
- A kit for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included. The kit also includes at least one isolator, wherein: each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn. The kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator. The additionally includes the transfer syringe, wherein, between the first centrifuging stage and the second centrifuging stage, the transfer syringe is configured to transfer the plasma from the at least one separator tube and into the at least one isolator by: being inserted through the cap of each separator tube of the at least one separator tube to withdraw the plasma from within the at least one separator tube; and being inserted through the septum cap of each isolator of the at least one isolator to inject the plasma into the at least one isolator.
- The disclosure will be better understood and when consideration is given to the drawings and the detailed description which follows. Such description makes reference to the annexed drawings wherein:
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FIG. 1 is an overview block diagram of aspects of an example system and method of isolating α2M from whole blood in preparation for delivery by injection. -
FIGS. 2 a, 2 b, 2 c, 2 d, 2 e, 2 f, 2 g, 2 h, 2 i and 2 j , together, provide a more detailed presentation of aspects of the example system and method ofFIG. 1 . -
FIG. 3 provides a flow chart of the method ofFIG. 1 . - In the following detailed description, reference is made to the accompanying drawings that form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.
- Disclosed herein is an α2M molecule isolation system implementing a method for isolating of α2M molecules from whole blood of a patient in preparation for use in treating a musculoskeletal condition of that patient.
- A method for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.
- A kit for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included. The kit also includes at least one isolator, wherein: each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn. The kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator. The additionally includes the transfer syringe, wherein, between the first centrifuging stage and the second centrifuging stage, the transfer syringe is configured to transfer the plasma from the at least one separator tube and into the at least one isolator by: being inserted through the cap of each separator tube of the at least one separator tube to withdraw the plasma from within the at least one separator tube; and being inserted through the septum cap of each isolator of the at least one isolator to inject the plasma into the at least one isolator.
- Turning to
FIG. 1 , an α2Mmolecule isolation system 1000 may include one or more of awhole blood syringe 200, a set ofmultiple separator tubes 300, a transfer device 400, acentrifuge 500, atransfer syringe 600, one ormore isolators 700, and/or an injectatesyringe 800. Thus thesystem 1000 may be implemented as a kit that is made up of a relatively small number of relatively small and lightweight components that are able to be more feasibly transported within a vehicle used by medical personnel (e.g., a doctor, veterinarian, medical technician, nurse, etc.). Additionally, and as will be explained in greater detail, thesystem 1000 enables the isolation of α2M molecules for injection into a joint or other musculoskeletal structure in less time than is possible in the prior art. For sake of clarity, it should be noted that the one ormore isolators 700 depicted and discussed in the present application were each earlier referred to as a “centrifugal concentrator” in the aforementioned U.S. Provisional Application 63/209,685 filed Jun. 11, 2021, the disclosure of which is incorporated herein by reference for all purposes. - Still referring to
FIG. 1 , the isolation of α2M molecules for use in treating a musculoskeletal condition begins with use of thewhole blood syringe 200 to draw an amount of whole blood from the patient to be treated (regardless of whether the patient is a human being or other form of animal), and then convey portions of that blood into each ofmultiple separator tubes 300. The set ofseparator tubes 300 may then be placed within thecentrifuge 500 to be subjected to centrifugal force for a first predetermined period of time (i.e., a first stage of centrifuging) to cause separation of the blood plasma containing the α2M molecules from other components of the whole blood with the aid of a separator gel incorporated into each of theseparator tubes 300. Following such separation of the plasma from the other blood components, one or both of a transfer device 400 and atransfer syringe 600 may then be used to retrieve the separated blood plasma from each of theseparator tubes 300, and transfer that plasma to one ormore isolators 700. The one ormore isolators 700 may then be placed within thecentrifuge 500 to be subjected to centrifugal force for a second predetermined period of time (i.e., a second stage of centrifuging) to cause isolation of the α2M molecules from the plasma with the aid of a membrane filter incorporated into eachisolator 700. Following such isolation of the α2M molecules, theinjectate syringe 800 may then be used to retrieve the α2M molecules from the one ormore isolators 700 in preparation for injecting the now isolated α2M molecules into a joint or other musculoskeletal structure of the patient. - Turning to
FIG. 2A , as depicted, the set ofseparator tubes 300 may be either a set ofnon-vacuum separator tubes 300 a or a set ofvacuum separator tubes 300 b. Each of the different types ofseparator tube cap 310 to at least maintain sterile conditions therein. Thecap 310 may be formed from a relatively flexible material that enables a hollow needle to penetrate therethrough for transferring gases and/or fluids into and/or out of the interior of each of theseparator tubes - In embodiments of the
system 1000 that include the set ofvacuum separator tubes 300 b, each of thevacuum separator tubes 300 b may be a VACUTAINER® tube of a type offered by Becton, Dickson and Company of Franklin Lakes, New Jersey, USA. As will be familiar to those skilled in the art, each suchvacuum separator tube 300 b, in its new and unused condition, may be pre-provided with a vacuum therein that the seal provided by thecap 310 is used to maintain. - Regardless of which of the
separator tubes separator tubes whole blood 110 that may be safely drawn from the patient, the type and/or severity of the musculoskeletal condition that is to be treated, and/or the maximum quantity ofseparator tubes centrifuge 500 at a time. Thus, it is contemplated that thesystem 1000 may be offered in differently-sized variants of kits, such as a smaller variant of kit that may include 1 to 4separator tubes separator tubes separator tubes - A
plunger 220 of thewhole blood syringe 200 may be operated to drawwhole blood 110 from a blood vessel of a patient (whether a human being or other form of animal) and into thewhole blood syringe 200 via aneedle 211 thereof. Thewhole blood syringe 200 may include a human-readable scale by which the volume of whole blood that is drawn is able to be measured as theplunger 220 is so operated to ensure that just the amount ofwhole blood 110 that is needed for the chosen quantity ofseparator tubes whole blood 110 is drawn, thewhole blood syringe 200 may then be used to inject a portion of the drawn whole blood into each of theseparator tubes cap 310 via theneedle 211. - As additionally depicted, in some embodiments, and prior to being used to draw
whole blood 110 from the patient, thewhole blood syringe 200 may be partially pre-filled (e.g., by the nurse, medical technician, veterinarian technician, doctor, veterinarian, etc.) with an amount of an anticoagulant 250, such as a citrate dextrose solution (ACD-A), to prevent the drawn whole blood from coagulating therein. - Turning to
FIG. 2B , each of the different types ofseparator tube separator gel 350 disposed toward the end opposite the end that is closed with thecap 310. Thus, as depicted, following the collection and storage of thewhole blood 110 among the set ofseparator tubes FIG. 2A , the portion of thewhole blood 110 within each of theseparator tubes cap 310 at one end and theseparator gel 350 at the other end. - With the set of
separator tubes whole blood 110, the set ofseparator tubes centrifuge 500 to be subjected to centrifugal force for a first period of time that is deemed sufficient to fully separate theplasma 113 thereof from the red andwhite blood cells 111 thereof. More specifically, and as depicted, thecentrifuge 500 may be used in conjunction with theseparator gel 350 to effect such a separation of components of thewhole blood 110. Thus, when such isolation of theplasma 113 is complete, theseparator gel 350 within each of theseparator tubes plasma 113 from the red andwhite blood cells 111, thereby preventing theseblood components - As depicted, and as will be familiar to those skilled in the art, the
centrifuge 500 may include arotor 553 that defines a set of holdingpositions 530 that each have a shape and dimensions selected to hold a tube of matching shape and dimensions, such as one of theseparator tubes positions 530, as defined by therotor 553, may be selected to enable various quantities of such tubes to be distributed among the holdingpositions 530 in a manner that distributes the weight thereof in a balanced manner that enables relatively smooth operation of thecentrifuge 500. - As will also be familiar to those skilled in the art, it may be that the depicted
rotor 553 is exchangeable within one or more other rotors to thereby enable the centrifuge to reconfigured to work with various different quantities and/or combinations of various tubes and/or other varieties of containers of differing shapes and/or sizes. Alternatively or additionally, it may be that thecentrifuge 500 is fitted with (or otherwise includes) a rotor with 2 or more “buckets.” Each such bucket may be able to be fitted with any of a variety of differing types of holder that may each be designed to provide holding position(s) for a differing quantity of and/or combination of various tubes and/or other varieties of containers of differing shapes and/or sizes. - Turning to
FIG. 2C , as depicted, in some embodiments of thesystem 1000, the transfer device 400 may be a dual-flow device 400 a. Alternatively, in other embodiments of thesystem 1000, the transfer device 400 may be a three-way valve 400 b. - Each of the different types of
transfer device separator tube port 430, asyringe port 460, and a filteredair port 490. As is about to be described, each of the different types oftransfer device external air 990 surrounding thetransfer device air filter 450 at the filteredair port 490 and conveyed to aseparator tube separator tube port 430 aspart enabling plasma 113 to be transferred from theseparator tube transfer syringe 600 coupled to thesyringe port 460. - It is envisioned that the interior volume of the
transfer syringe 600 is sufficiently large that all of the sum total of the amounts of theplasma 113 isolated within all of theseparator tubes transfer syringe 600. As a result, it is envisioned that thetransfer syringe 600 is to remain connected to thesyringe port 460 by itsend connector 610 throughout the time that theplasma 113 is being transferred from each of thevacuum containers 100, and into thetransfer syringe 600. -
FIG. 2D depicts aspects of the manner in which the dual-flow device 400 a enables a simultaneous transfer of filteredair 994 into aseparator container plasma 113 out of theseparator container plasma 994 to thetransfer syringe 600. As depicted, theseparator tube port 430 may incorporate both anair needle 439 and aplasma needle 431 that are each positioned to penetrate through thecap 310 of aseparator tube separator tube syringe port 460 may be configured to form a connection with anend connector 610 carried at one end of thetransfer syringe 600. - As depicted, with a
separator tube separator tube port 430 such that theneedles cap 310 thereof, and with theend connector 610 of thetransfer syringe 600 coupled to thesyringe port 460, there may be an initial equalization of pressures thereamong. More specifically, and especially where avacuum separator tube 300 b coupled to theseparator tube port 430,external air 990 may be drawn into the dual-flow device 400 a through the filteredair port 490, and conveyed into aseparator tube separator tube port 430 via theair needle 439. Pulling theplunger 660 of thetransfer syringe 600 away from theend connector 610 thereof may then drawplasma 994 from within theseparator tube transfer syringe 660, via theplasma needle 431 and theend connector 610. In turn, morefiltered air 994 may be drawn into theseparator tube plasma 994 that is so drawn out. -
FIG. 2E depicts aspects of the manner in which the three-way valve 400 b enables a selective transfer of filteredair 994 into aseparator container plasma 113 out of theseparator container plasma 994 to thetransfer syringe 600. As depicted, and unlike the dual-flow device 400 a, theseparator tube port 430 of the three-way valve 400 b may incorporate just asingle needle 431 that is positioned to penetrate through thecap 310 of aseparator tube separator tube flow device 400 a, thesyringe port 460 may be configured to form a connection with anend connector 610 carried at one end of thetransfer syringe 600. - Also unlike the dual-
flow device 400 a, the three-way valve 400 b may incorporate a manually-operable valve (not specifically shown) of a type that is operable between at least two positions, where each position of the at least two positions causes one of the threeports - As depicted, for each
separator tube separator tube port 430, the transfer ofplasma 113 therefrom, and into thetransfer syringe 600, may begin with the three-way valve 400 b being operated to close off theseparator tube port 430, thereby connecting thesyringe port 460 to the filteredair port 490. With theseparator tube port 430 so closed off, theplunger 660 of thetransfer syringe 600 may be operated to draw filteredair 994 into thetransfer syringe 600. More precisely, theplunger 660 of thetransfer syringe 600 may be operated to causeexternal air 990 that surrounds the three-way valve 400 b to be drawn in through theair filter 450, thereby being filtered to become thefiltered air 994 that is drawn into thetransfer syringe 600. - With an amount of such
filtered air 994 now within thetransfer syringe 600, the three-way valve 400 b may then operated to close off the filteredair port 490, thereby connecting thesyringe port 460 to theseparator tube port 430. With the filteredair port 490 so closed off, theplunger 660 of thetransfer syringe 600 may be operated to send filteredair 994 out of thetransfer syringe 600, through the three-way valve 400 b, through thesingle needle 431, and into theseparator tube separator tube port 430. With filteredair 994 so conveyed into theseparator tube plunger 660 of thetransfer syringe 600 may then be operated to draw most, if not all, of theplasma 113 out of theseparator tube single needle 431, through the three-way valve 400 b, and intotransfer syringe 600. - Referring back to both
FIGS. 2D and 2E , it should be noted, that such transfers ofplasma 113 from theseparation tubes transfer syringe 600 may need to be performed with the depicted combination of theseparation tube transfer device transfer syringe 600 held in an orientation in which theseparation tube transfer syringe 600. - Turning
FIG. 2F , following the transfer ofplasma 113 out of each of theseparation tubes transfer syringe 600, thetransfer syringe 600 may then be disconnected from thetransfer device needle 611 may be connected to theend connector 610 of thetransfer syringe 600 in preparation for injecting theplasma 113 into theisolator 700. - Turning to
FIG. 2G , as depicted, theisolator 700 may include a combination of afirst cylinder 701 and asecond cylinder 702. Both of thesecylinders - One end of the
first cylinder 701 may be sealed (or sealable) with aseptum cap 710 that may provide a self-sealing aperture through which a needle or other form of tube of relatively small diameter tube may be inserted to effect the transfer of gases and/or liquids into and/or out of the interior volume of thefirst cylinder 701. The other end of thefirst cylinder 701 may incorporate amembrane filter 750. In some embodiments, themembrane filter 750 may have a filter diameter ranging from 100 kD to 500 kD. - The
second cylinder 702 may be configured to make theisolator 700 more amenable for use with thecentrifuge 700. More specifically, one end of thesecond cylinder 702 may be closed off with a conical end to ease insertion into thecentrifuge 500, while the other end may be open to enable the twocylinders first cylinder 701 that includes themembrane filter 750 therein. - It should be noted, and as depicted, in some embodiments, the
isolator 700 may be of anextended length variation 700 a in which the volume of thefirst cylinder 701 is increased by sealing the end opposite themembrane filter 750 with an extended variant of theseptum cap 710 that provides a cylindrical extension to the cylindrical wall of thefirst cylinder 701 to increase the length of thefirst cylinder 701. Alternatively, in other embodiments, theisolator 700 may be of astandard length variation 700 b in which the volume of thefirst cylinder 701 is not so increased. More precisely, instead of sealing the end opposite themembrane filter 750 with the extended variant of theseptum cap 710, a standard variant of theseptum cap 710 is used that does not provide the cylindrical extension. - Turning to
FIG. 2H , with the isolator 700 a or 700 b assembled, and with theneedle 611 connected to endconnector 610 of thetransfer syringe 600, theneedle 611 may then be inserted through the aperture of theseptum cap 710. Theplunger 660 of thetransfer syringe 600 may then be operated to transfer theplasma 113 out of thetransfer syringe 600, and into thefirst cylinder 701 through theneedle 611 and the aperture of theseptum cap 710. - Turning to
FIG. 2I , after theplasma 113 has been transferred into thefirst cylinder 701, the still assembledisolator 700 may be placed within thecentrifuge 500 to be subjected to centrifugal force for a second period of time that is deemed sufficient to fully separate theα2M molecules 117 from the rest of theplasma 113 originally transferred into thefirst cylinder 701. More specifically, and as depicted, thecentrifuge 500 may be used in conjunction with themembrane filter 750 to effect such a separation of components of theplasma 113. Thus, when such isolation of theα2M molecules 117 is complete, theα2M molecules 117 should remain within thefirst cylinder 701, while the other components of theplasma 114 should be retained within thesecond cylinder 702 as the depictedwaste plasma 114. - In a manner similar to what was discussed in reference to
FIG. 2B , thecentrifuge 500 may include arotor 557 that defines a pair of holdingpositions 570 that each have a shape and dimensions selected to hold a tube of matching shape and dimensions, such as theisolator 700. As also depicted, it may be that the pair of such holdingpositions 570, as defined by therotor 557, may be positioned to enable the placement of a pair of theisolators 700 at locations that distribute the weight thereof in a balanced manner that enables relatively smooth operation of thecentrifuge 500. - Further, and as also previously discussed, there may be various variants of the
system 1000 offered to provide a range of capacities, such as the aforedescribed smaller, mid-size and larger variants with different quantities ofseparator tubes isolators 700. More specifically, and by way of example, it may be that the aforedescribed smaller and mid-sized variants include asingle isolator 700, while the larger variant includes two of theisolators 700. In such variants that include just asingle isolator 700, a dummy weight of a shape and size similar to theisolator 700 may be included to provide a counterbalance to the weight of theisolator 700 withplasma 113 therein to enable balancing of thecentrifuge 500. - However, as an alternative to providing a dummy weight, it may be that all of the aforedescribed size variants of the
system 1000 may be provided with a pair ofisolators 700. It may be that, for the aforedescribed smaller and mid-sized variants, the second one of the twoisolators 700 is to be filled with water to serve the purpose of being the counterbalance. - As will also be familiar to those skilled in the art, it may be that the depicted
rotor 553 is exchangeable within one or more other rotors to thereby enable the centrifuge to reconfigured to work with various different quantities and/or combinations of various tubes and/or other varieties of containers of differing shapes and/or sizes. Alternatively or additionally, it may be that thecentrifuge 500 is fitted with (or otherwise includes) a rotor with 2 or more “buckets.” Each such bucket may be able to be fitted with any of a variety of differing types of holder that may each be designed to provide holding position(s) for a differing quantity of and/or combination of various tubes and/or other varieties of containers of differing shapes and/or sizes. - It should be noted that such use of the
isolator 700 with thecentrifuge 500 to perform the separation of theα2M molecules 117 from the rest of theplasma 113 originally transferred into thefirst cylinder 701 has been found to be faster than the prior art use of a peristaltic pump. Thecentrifuge 500 is also a far simpler, more durable and far less expensive piece of equipment than a peristaltic pump such that equipping a vehicle used to make house calls with thecentrifuge 500 is far more feasible. - Turning to
FIG. 2J , following such isolation of theα2M molecules 117, aneedle 811 connected to anend connector 810 of aninjectate syringe 800 may be inserted through the aperture of theseptum cap 710. With theneedle 811 so inserted, aplunger 880 of theinjectate syringe 800 may then be operated to transfer theα2M molecules 117 from thefirst cylinder 701, and into theinjectate syringe 800. Where more than oneisolator 700 is used to isolate theα2M molecules 117 of a particular patient, such operations may be repeated to transfer theα2M molecules 117 out of eachsuch isolator 700. - In some embodiments, with the most (if not all) of the
α2M molecules 117 so transferred into theinjectate syringe 800, theinjectate syringe 800 may then be used directly to inject theα2M molecules 117 into a joint or other musculoskeletal structure of the patient. Alternatively, theinjectate syringe 800 may be used to transfer theα2M molecules 117 into one or more other syringes (not shown) that may then be used to inject theα2M molecules 117 into a joint or other musculoskeletal structure of the patient. As still another alternatively, theinjectate syringe 800 may be used to transfer theα2M molecules 117 into storage vials or still other container(s) (not shown) for temporary storage in preparation for theα2M molecules 117 to be so injected into a joint or other musculoskeletal structure of the patient at a later time. -
FIG. 3 is aflowchart 2100 depicting aspects of the operation of an α2M molecule isolation system to perform a method of isolating α2M molecules from a patient's whole blood for use in treating a musculoskeletal condition of that patient. - At 2110, whole blood may be drawn from a patient (e.g., a human being or other form of animal) who/that may be suffering from a musculoskeletal condition affecting a joint or other musculoskeletal structure. As has been discussed, a syringe inserted into an artery or vein of the patient may be used (e.g., the
whole blood syringe 200 of the system 1000). - At 2112, the whole blood may be transferred to one or more separator tubes that may each be preloaded with a separator gel (e.g., one or more of the
separator tubes - At 2120, the separator tube(s) may be placed within a centrifuge (e.g., the centrifuge 500), and the centrifuge may be operated to exert centrifugal force on the separator tube(s) in a first stage of centrifuging. In this way, a combination of the exerted centrifugal force and the separator gel within each separator tube may be used to separate the plasma of the whole blood from at least the red and white blood cells of the whole blood.
- At 2130, at least a transfer syringe (e.g., the transfer syringe 600) may be used to retrieve the plasma from within the separator tube(s), and to transfer the plasma into at least one isolator incorporating a filter (e.g., at least one of the
isolator 700 incorporating the filter 750). As has been discussed, just as the quantity of separator tubes may vary across multiple variations of the system, it may be that the quantity of isolators also varies in a manner that is at least partially correlated to the quantity of separator tubes. Alternatively, it may be that a pair of isolators is regularly included with the expectation that, where they are not both used, the unused one may be filled with an amount of water or other substance to serve as a counterbalance to the one that is used during a second stage of centrifuging. - At 2140, the isolator(s) may be placed within the centrifuge, and the centrifuge may be operated to exert centrifugal force on the isolator(s) in the aforementioned second stage of centrifuging. In this way, a combination of the exerted centrifugal force and the filter within each isolator that is filled with plasma may be used to isolate the α2M molecules from other components of the plasma. Again, where just one isolator is filled with plasma, a counterbalancing weight, or other isolator that is filled with water or another substance to serve as a counterbalancing weight, may be required to balance the centrifuge.
- At 2150, an injectate syringe (e.g., the injectate syringe 800) may be used to retrieve the α2M molecules from within the isolator(s).
- At 2160, the patient may then be treated with the α2M molecules, either with injection(s) directly from the injectate syringe, or from other syringe(s) to which the α2M molecules may be transferred from the injectate syringe. Alternatively, at 2160, the α2M molecules may be stored for later use in such treatment.
- There is thus disclosed an α2M molecule isolation system and method for isolating of α2M molecules from whole blood of a patient in preparation for use in treating a musculoskeletal condition of that patient.
- A method for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes: depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.
- The method may further include: retrieving at least a portion of the α2M molecules from within the at least one isolator; and injecting at least the portion of the α2M molecules into a musculoskeletal structure of a patient from which the whole blood was drawn.
- Each separator tube of the at least one separator tube may include an elongate transparent tube that defines an opening at one end that is sealed with a cap, and the cap may be formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn. Depositing the whole blood into at least one separator tube may include: inserting a needle of the syringe through the cap of each separator tube of the at least one separator tube; and injecting at least a portion of the whole blood into each separator tube of the at least one separator tube from within the syringe.
- Each separator tube of the at least one separator tube may include either a non-vacuum separator tube, or a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
- The method may further include: using the syringe to draw the whole blood from a patient into which the α2M molecules are to be injected; and partially pre-filling the syringe with an anticoagulant before using the syringe to draw the whole blood from the patient.
- Subjecting the at least one separator tube to the first centrifugal force in the first centrifuging stage may include placing the at least one separator tube within a first holder of a centrifuge, and operating the centrifuge to exert the first centrifugal force on the at least one separator tube; subjecting the at least one isolator to the second centrifugal force in the second centrifuging stage may include placing the at least one isolator within a second holder of the centrifuge, and operating the centrifuge to exert the second centrifugal force on the at least one isolator; the first holder may include either a first removable holder configured to be inserted into a bucket of the centrifuge, or a first exchangeable rotor of the centrifuge; and the second holder may include either a second removable holder configured to be inserted into a bucket of the centrifuge, or a second exchangeable rotor of the centrifuge.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may include: using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; and using the transfer syringe to deposit the one or more portions of the plasma into the at least one isolator.
- The at least one separator tube, the centrifuge, the transfer syringe and the at least one isolator, together, may form a kit for isolating the α2M molecules from the whole blood; and multiple versions of the kit may be defined by at least one of a quantity of separator tubes included in the at least one separator tube and a quantity of isolators included in the at least one isolator.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include: coupling the transfer syringe to a syringe port of a transfer device; coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the transfer device, wherein the separator tube port comprises at least one hollow needle configured to simultaneously couple the separator tube port to the syringe port and to a filtered air port of the transfer device; and while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least one portion of the one or more portions of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through an air filter at the filtered air port and into the separator tube through the transfer device.
- Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include coupling the transfer syringe to a syringe port of a three-way valve, coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the three-way valve, and while each separator tube of the at least one separator tube is coupled to the separator tube port, performing operations including: with the three-way valve operated to couple a filtered air port of the three-way valve to the syringe port, operating a plunger of the transfer syringe to draw air through an air filter at the filtered air port, through the three-way valve, and into the transfer syringe; and with the three-way valve operated to couple the separator tube port to the syringe port, operating the plunger of the transfer syringe to inject the filtered air into the separator tube through the three-way valve, and to withdraw at least one of the one or more portions of the plasma from the separator tube and into the transfer syringe through the three-way valve.
- Each isolator of the at least one isolator may include a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; a first end of the first cylindrical wall of the first cylinder may define an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder may be closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap may be formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn. Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include: using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; inserting a needle of the transfer syringe through the septum cap of each isolator of the at least one isolator; and injecting the one or more portions of the plasma into the first interior space from within the transfer syringe. Isolating the α2M molecules from other components of the plasma within the at least one isolator may include isolating the α2M molecules from other components within the first interior space of each isolator of the at least one isolator from the other components of the plasma within the second interior space of each isolator of the at least one isolator.
- The septum cap may further include a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
- A kit for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood includes at least one separator tube, wherein: each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap; each separator tube of the at least one separator tube contains an amount of separator gel; the cap is formed from a flexible material that allows a hollow needle of a transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and the kit is available in multiple versions that are differentiated by at least a quantity of separator tubes that are included. The kit also includes at least one isolator, wherein: each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; each isolator of the at least one isolator comprises a filter; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter; and at least a portion of the septum cap is formed from a flexible material that allows the hollow needle of the transfer syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn. The kit further includes a centrifuge that is configured to: subject the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; and subject the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator. The additionally includes the transfer syringe, wherein, between the first centrifuging stage and the second centrifuging stage, the transfer syringe is configured to transfer the plasma from the at least one separator tube and into the at least one isolator by: being inserted through the cap of each separator tube of the at least one separator tube to withdraw the plasma from within the at least one separator tube; and being inserted through the septum cap of each isolator of the at least one isolator to inject the plasma into the at least one isolator.
- Each separator tube of the at least one separator tube may include either a non-vacuum separator tube, or a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
- The centrifuge may further include at least one exchangeable rotor to enable the centrifuge to be used in the first centrifuging stage and the second centrifuging stage by exchanging the at least one exchangeable rotor.
- The centrifuge may further include a rotor that is configured to define multiple buckets into which exchangeable holders of differing configurations may be installed to enable the centrifuge to be used in the first centrifuging stage and the second centrifuging stage by exchanging holders within the multiple buckets.
- The kit may further include a transfer device, wherein: the transfer device may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port; and while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe may be able to be operated to withdraw at least a portion of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through the air filter at the filtered air port and into the separator tube through the transfer device.
- The kit may further include a three-way valve, wherein: the three-way valve may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port. While each separator tube of the at least one separator tube is coupled to the separator tube port, the three-way valve and a plunger of the transfer syringe may be able to be operated to perform operations including: with the three-way valve operated to couple a filtered air port of the three-way valve to the syringe port, the plunger of the transfer syringe is able to be operated to draw air through the air filter at the filtered air port, through the three-way valve, and into the transfer syringe; and with the three-way valve operated to couple the separator tube port to the syringe port, the plunger of the transfer syringe is able to be operated to inject the filtered air into the separator tube through the three-way valve, and to withdraw at least a portion of the plasma from the separator tube and into the transfer syringe through the three-way valve.
- Injecting the plasma into the at least one isolator may include injecting at least a portion of the plasma into the first interior space within the first cylinder of each isolator of the at least one isolator; and isolating the α2M molecules from other components of the plasma within the at least one isolator may include isolating the α2M molecules from other components within the first interior space of each isolator of the at least one isolator from the other components of the plasma within the second interior space within each isolator of the at least one isolator.
- The septum cap may further include a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
Claims (18)
1. A method for isolating Alpha-2 Macroglobulin (α2M) molecules from whole blood comprising:
depositing whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel;
subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules;
transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and
subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.
2. The method of claim 1 , further comprising:
retrieving at least a portion of the α2M molecules from within the at least one isolator; and
injecting at least the portion of the α2M molecules into a musculoskeletal structure of a patient from which the whole blood was drawn.
3. The method of claim 1 , wherein:
each separator tube of the at least one separator tube comprises an elongate transparent tube that defines an opening at one end that is sealed with a cap;
the cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and
depositing the whole blood into at least one separator tube comprises:
inserting a hollow needle of the syringe through the cap of each separator tube of the at least one separator tube; and
providing at least a portion of the whole blood into each separator tube of the at least one separator tube through the hollow needle.
4. The method of claim 3 , comprising:
using a syringe comprising the hollow needle to draw the whole blood from a patient into which the α2M molecules are to be injected; and
partially pre-filling the syringe with an anticoagulant before using the syringe to draw the whole blood from the patient.
5. The method of claim 4 , wherein the anticoagulant comprises a citrate dextrose solution (ACD-A).
6. The method of claim 3 , wherein:
each separator tube of the at least one separator tube comprises a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
7. The method of claim 1 , wherein:
subjecting the at least one separator tube to the first centrifugal force in the first centrifuging stage comprises placing the at least one separator tube within a first holder of a centrifuge, and operating the centrifuge to exert the first centrifugal force on the at least one separator tube; and
subjecting the at least one isolator to the second centrifugal force in the second centrifuging stage comprises placing the at least one isolator within a second holder of the centrifuge, and operating the centrifuge to exert the second centrifugal force on the at least one isolator;
8. The method of claim 7 , wherein:
the first holder comprises either a first removable holder configured to be inserted into a bucket of the centrifuge, or a first exchangeable rotor of the centrifuge; and
the second holder comprises either a second removable holder configured to be inserted into a bucket of the centrifuge, or a second exchangeable rotor of the centrifuge.
9. The method of claim 7 , wherein transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator comprises:
using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; and
using the transfer syringe to deposit the one or more portions of the plasma into the at least one isolator.
10. The method of claim 9 , wherein:
the at least one separator tube, the centrifuge, the transfer syringe and the at least one isolator, together, form a kit for isolating the α2M molecules from the whole blood; and
multiple versions of the kit are defined by at least one of a quantity of separator tubes included in the at least one separator tube and a quantity of isolators included in the at least one isolator.
11. The method of claim 10 , wherein the multiple versions of the kit include a kit comprising 4, 8 or 16 separator tubes.
12. The method of claim 10 , the kit further includes a dummy isolator of a shape and size similar to the at least one separator tube to provide a counterbalance to the weight of a single separator tube of the at least one separator tube after the single separator tube is filled with plasma to enable balancing of the centrifuge.
13. The method of claim 1 , wherein transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator further comprises:
coupling a transfer syringe to a syringe port of a transfer device;
coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the transfer device, wherein the separator tube port comprises at least one hollow needle configured to simultaneously couple the separator tube port to the syringe port and to a filtered air port of the transfer device;
while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least one portion of the one or more portions of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through an air filter at the filtered air port and into the separator tube through the transfer device; and
following transfer of the one or more portions of the plasma from each separator tube of the at least one separator tube, using the transfer syringe to inject the one or more portions of the plasma into the at least one isolator.
14. The method of claim 13 , wherein the at least one hollow needle comprises:
a first hollow needle coupling the separator tube port to the syringe port; and
a second hollow needle coupling the separator tube port to the filtered air port.
15. The method of claim 1 , wherein transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator further comprises:
coupling a transfer syringe to a syringe port of a three-way valve;
coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the three-way valve;
while each separator tube of the at least one separator tube is coupled to the separator tube port, performing operations comprising:
with the three-way valve operated to couple a filtered air port of the three-way valve to the syringe port, operating a plunger of the transfer syringe to draw air through an air filter at the filtered air port, through the three-way valve, and into the transfer syringe; and
with the three-way valve operated to couple the separator tube port to the syringe port, operating the plunger of the transfer syringe to inject the filtered air into the separator tube through the three-way valve, and to withdraw at least one of the one or more portions of the plasma from the separator tube and into the transfer syringe through the three-way valve; and
following transfer of the one or more portions of the plasma from each separator tube of the at least one separator tube, using the transfer syringe to inject the one or more portions of the plasma into the at least one isolator.
16. The method of claim 1 , wherein:
each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall;
a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a septum cap, and a second end of the first cylindrical wall is closed with the filter;
a first end of the second cylindrical wall of the second cylinder is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter;
at least a portion of the septum cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn;
transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator comprises:
using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube;
inserting a needle of the transfer syringe through the septum cap of each isolator of the at least one isolator; and
injecting the one or more portions of the plasma into the first interior space from within the transfer syringe; and
isolating the α2M molecules from other components of the plasma within the at least one isolator comprises isolating the α2M molecules from other components within the first interior space of each isolator of the at least one isolator from the other components of the plasma within the second interior space of each isolator of the at least one isolator.
17. The method of claim 16 , wherein the septum cap further comprises a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
18. The method of claim 16 , wherein the filter of each isolator of the at least one isolator has a molecular weight cut off ranging from 100 kD to 500 kD.
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US18/215,498 US20230338628A1 (en) | 2021-06-11 | 2023-06-28 | System and method for isolating alpha 2m molecules |
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US3300051A (en) * | 1963-09-26 | 1967-01-24 | Internat Equipment Co | Filter tube for use in a centrifuge |
US3610241A (en) * | 1969-08-15 | 1971-10-05 | Romeo Lemarie | Syringe guide and indicator |
US3939822A (en) * | 1974-08-14 | 1976-02-24 | Jack Markowitz | Disposable blood collection and filtering device |
US4957637A (en) * | 1988-05-23 | 1990-09-18 | Sherwood Medical Company | Serum separator system for centrifuge with piercable membrane |
US5599558A (en) * | 1989-09-15 | 1997-02-04 | Curative Technologies, Inc. | Selecting amounts of platelet releasate for efficacious treatment of tissue |
US6471069B2 (en) | 1999-12-03 | 2002-10-29 | Becton Dickinson And Company | Device for separating components of a fluid sample |
EP1244477A2 (en) * | 1999-12-29 | 2002-10-02 | Regeneration Technologies, Inc. | System for reconstituting pastes and methods of using same |
WO2005014173A1 (en) * | 2003-08-05 | 2005-02-17 | Becton, Dickinson And Company | Device and methods for collection of biological fluidsample and treatment of selected components |
AT502522A3 (en) | 2005-10-04 | 2007-12-15 | Greiner Bio One Gmbh | DISCONNECTION DEVICE, RECORDING DEVICE AND METHOD OF DISCONNECTING |
US8357296B2 (en) * | 2007-09-24 | 2013-01-22 | Emd Millipore Corporation | Centrifugal filter |
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US9555171B2 (en) | 2010-09-30 | 2017-01-31 | Depuy Mitek, Llc | Methods and devices for collecting separate components of whole blood |
CN101992136B (en) | 2010-09-30 | 2012-09-05 | 何洪敏 | Combined centrifuge tube for preparing cell wax blocks by using exfoliated cells |
WO2013111130A1 (en) * | 2012-01-23 | 2013-08-01 | Estar Technologies Ltd | A system and method for obtaining a cellular sample enriched with defined cells such as platelet rich plasma(prp) |
EP2827882B1 (en) | 2012-02-21 | 2020-04-08 | Cytonics Corporation | Systems, compositions, and methods for transplantation |
US9352021B2 (en) | 2013-08-28 | 2016-05-31 | Cytonics Corporation | Systems, compositions, and methods for transplantation and treating conditions |
FR3018450B1 (en) * | 2014-03-11 | 2016-04-15 | Lab Francais Du Fractionnement | PROCESS FOR THE PREPARATION OF HUMAN PLASMA PROTEINS |
WO2016081834A2 (en) | 2014-11-20 | 2016-05-26 | Cytonics Corporation | Therapeutic variant alpha-2-macroglobulin compositions |
BR112017015758A2 (en) * | 2015-01-22 | 2018-03-27 | Univ California | bone marrow and platelet-rich plasma cell separation and removal methods and devices |
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CN109206506A (en) | 2018-03-16 | 2019-01-15 | 王小虎 | The preparation of modified ultrafiltration centrifugal process is rich in the device and method of alpha2 Macroglobulin serum |
US11534092B2 (en) * | 2019-03-26 | 2022-12-27 | National Guard Health Affairs | Blood collection tube |
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