Patent Application
20140255906
The present disclosure relates generally to blood preservation, storage and transfusion.
Whole blood and blood components from a donor are commonly preserved and stored under refrigeration until they are required by a patient receiving the transfusion. Blood storage under refrigeration generally depletes the metabolites used by the blood during circulation in the body to maintain red blood cell (RBC) viability and function, and at the same time generates waste products that would otherwise be removed in the body. Sterile solutions containing anticoagulant and/or preservative systems are generally used in an attempt to maintain RBC viability and decrease the possibility of bacterial contamination.
Alterations in RBC biochemistry and physical properties that occur during storage are generally referred to as “storage lesions.” Refrigeration slows but does not stop RBC metabolism, and RBCS in storage continue to metabolize glucose through the anaerobic glycolysis pathway, producing two adenosine diphosphates (ADPs, from adenosine triphosphate or ATP) and a lactic acid during the metabolism of each glucose to 2,3-biphosphoglycerate (BPG, also referred to as DPG) or 1-phosphoglycerate (PG). BPG, which is widely accepted as necessary for allostearic facilitation of oxygen release from RBC in the body, is favored by a higher pH, whereas a lower pH favors PG, which has no effect on the oxygen dissociation curve. The tendency for pH in stored RBC to drop over time is only partially inhibited by the buffering capacity of the preservative and additive solutions currently in use.
ATP levels also decline during RBC storage, depleting at the expiration date to only from 45 to 86 percent of the original levels, depending on the storage additives used. While low ATP levels are associated with poor RBC viability, a high ATP level does not necessarily indicate good viability because of other types of storage lesions. Sodium and potassium leak through the membranes of the RBCs, elevating the potassium levels in the storage solution. BPG levels, generally associated with pH, may stay almost normal during the first week of storage, but also decline to the expiration date. Decreased BPG levels are associated with a left-shift in the oxygen dissociation curve of hemoglobin, resulting in an inhibited ability to release oxygen in the tissues of the recipient until circulation restores normal BPG levels, which can take up to 24 hours after transfusion.
Also, plasma hemoglobin levels continually increase due to RBC hemolysis that continues during storage. Blood ammonia levels also increase during storage. Further, RBCs manifest physical changes during storage, including the appearance of RBCs called echinocytes, which have multiple spiny projections; or the appearance of spherocytes, which take on a spherical shape as opposed to the normal biconcave disc shape of a healthy RBC.
RBCs in the body generally last about 120 days before hemolysis. However, the shelf life of RBCs in the available storage protocols is at most 3 to 6 weeks. Furthermore, recent studies have suggested that morbidity and mortality statistically increase with the length of storage of the RBCs, i.e., their storage age, prior to transfusion, especially after 1-2 weeks in storage.
Oxyhemoglobin (oxyHb) prevalent in arterial blood is diamagnetic with a reported susceptibility of −((0.13 to 0.65)×10−8 cgs emu/cm3Oe; whereas deoxyhemoglobin (deoxyHb) which occurs predominantly in venous blood, following oxygen release in the capillaries, is paramagnetic with a reported susceptibility of +(13 to 33)×10−8 cgs emu/cm3Oe. Methemoglobin, (metHb) in which the heme is essentially irreversibly oxidized, is also paramagnetic with susceptibility similar to that of oxyHb. The effects of strong magnetic fields, e.g., 30 to 100 kG, on blood have been reported in the literature as including orientation of red blood cells and platelets with the magnetic field direction, polymerization and alignment of fibrinogens, and increasing the apparent viscosity of blood. Mayrovitz et al., “Effects of a static magnetic field of either polarity on skin microcirculation,” Microvascular Research, vol. 69, pp. 24-27 (2005), reported a reduction in skin blood perfusion upon exposure of the patient to a neodymium magnet with a surface field of more than 4 kG.
There remains a long-felt and dire need in the art to inhibit the degradation of stored blood and blood components, to lengthen the shelf life, to improve the viability of RBCs in storage, to reduce the occurrence of complications associated with transfusions, and/or to reduce morbidity and mortality outcomes in transfusion recipients.
An aspect of the present invention is the improvement of the viability and/or shelf life of stored red blood cells (RBC or RBCs) by electromagnetically treating the blood in storage, e.g., by continuous or periodic application of electromagnetic stimulation, such as an electrical current, magnetic field, or combination thereof.
Another aspect of the present invention is an apparatus for storing blood comprising an electromagnetic generator to continuously or periodically generate electromagnetic stimulation in a blood storage compartment and/or blood flow path, e.g., an electrical current, magnetic field or combination thereof.
The inventor has determined that the deterioration of RBC in storage, i.e., the period of time following collection from a donor until transfusion into a recipient patient, may arise at least in part from the extended period of electromagnetic inactivity or quiescence, which is termed “electromagnetic senescence” herein. This phenomenon might be explained as a gradual degaussing or loss of surface polarization of the RBC, or a loss of magnetization of the heme centers in the hemoglobins, and/or a redistribution of polarity, although the invention is not to be limited by any particular theory.
The RBC in venous blood collected for blood banking and eventual transfusion, containing some deoxyhemoglobin, has an external surface orientation or polarity that helps keep the blood cells from sticking together due to the mutual repulsion of the like surface polarity. As the blood travels through the circulatory system, it is constantly cycled through bioelectromagnetic processing parameters that keep the heme irons magnetized and reconditioned for readily holding and releasing oxygen in repeated cycles through the cardiovascular circulatory system.
In the tissue or organ capillaries outside the lungs, the RBC are forced in close proximity to the internal surfaces of the capillary, oxygen is released and carbon dioxide taken on. The cells forming the capillary comprise a single-cell layer, and have bioelectromagnetic activity with intracellular electrical potential reported to be as much as 3 million ev/m in human cells. The capillary cells, and possibly to a lesser extent the surrounding tissue cells, are thus capable of bioelectromagnetic stimulation of the magnetically susceptible RBC, in addition to the electrical current incidental to the cardiac cycle and other neural and/or muscular activity. This is consistent with the observation that oxygen is more readily released in the vicinity of active muscles and/or organs where it is needed most.
One theory formed by the inventor, by which the present invention including the claims are not to be limited, is that the bioelectromagnetic stimulation may induce the hemoglobin in the magnetically susceptible RBC to roll or turn so that the external polarity is switched from negative or north (diamagnetic) to positive or south (paramagnetic) to facilitate release of the oxygen in the tissues. In the vicinity of the lungs and heart, the cardiac cycle can be a source of the bioelectromagnetic stimulation of the magnetically susceptible RBC, as well as the capillary cells, which are thought to stimulate the magnetization of the heme irons to facilitate carbon dioxide release and oxygen absorption.
Once the blood is withdrawn from a vein and collected, however, the RBC in conventional collection and storage systems and methodologies are no longer subjected to the repetitive bioelectromagnetic stimulation experienced in normal circulation through the body. Thus, the magnetic and electrical properties of the RBC in storage can be gradually altered, and the hemoglobin observed to rapidly deteriorate and lose the ability to selectively bind and release oxygen and carbon dioxide.
In one embodiment of the invention, RBC in stored blood or blood components is continuously or periodically subjected to electromagnetic stimulation, preferably on the order of biological electromagnetic stimulation, such as, for example, an electrical current and/or electromagnetic fields, similar in magnitude and phase characteristics to those experienced in the body, to constantly rejuvenate the RBC and maintain heme iron magnetization and/or external-internal polarity. In an embodiment, the applied electromagnetic stimulation serves to maintain the heme iron magnetization and/or surface magnetic polarity of the RBC, inhibiting electromagnetic senescence, preserving the RBC and inhibiting deterioration of the RBC.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and are not restrictive of the present disclosure, as claimed. In addition, structures and features described with respect to one embodiment can similarly be applied to other embodiments.
The accompanying drawings, which are incorporated in and constitute a part of this specification, provide illustrative embodiments of the present disclosure and, together with the description, serve to explain the principles of the disclosure.
In an embodiment, a method of storing red blood cells (RBC) comprises electromagnetically stimulating the RBC to improve viability.
In an embodiment, the RBC storage method comprises periodically or continuously passing an electric current through the stored RBC. In an embodiment, the electric current has amperage, voltage, wave form or a combination thereof corresponding to a cardiac cycle for the species of RBC. In embodiments, the current is direct current or alternating current. In an embodiment, the current is pulsed at a frequency from 0.001 to 10 Hz. In an embodiment, the current is supplied at a voltage potential between from 1 to 1000 millivolts.
In another embodiment, the RBC storage method comprises periodically or continuously applying a magnetic field to the RBC. In embodiments, the magnetic field comprises a static magnetic field, or an oscillating magnetic field, and the magnetic field can be a homogenous magnetic field or a heterogeneous magnetic field. In an embodiment, the magnetic field is within a range of from about 0.5 to about 500 Gauss, or within a range of from about 10 to about 100 Gauss. In an embodiment, the magnetic field is pulsed at a frequency from 0.001 to 10 Hz.
In one embodiment, the electromagnetic stimulation is applied to the RBC just prior to or during transfusion into the recipient.
In an embodiment, the RBC can be stored in the presence of an added anticoagulant, pH buffer, nutrient, preservative, pathogen inactivator or combination thereof.
In an embodiment, the RBC are stored in whole blood. The RBC can be stored, for example, in the presence of citrate-potassium-dextrose solution (CPD) such as CPD-1 or citrate-potassium-dextrose-adenine solution (CPDA) such as CPDA-1.
In another embodiment, the RBC can be separated from whole blood, e.g. by centrifugation or aphoresis. In an embodiment, the RBC can be stored in the presence of adenine-saline solution (AS), e.g., AS-1, AS-2, AS-3, AS-4, AS-5, AS-6, and so on.
In an embodiment, the method can include the step of inactivating pathogens, e.g., viruses, bacteria, parasites and so on, such as for example by adding a pathogen inactivator, such as in the Cerus INTERCEPT blood system, to the storage medium. Pathogen inactivators and inactivation methods are disclosed in U.S. Pat. No. 7,611,831, U.S. Pat. No. 7,293,985, US 2004/029897, US 2003/082510, US 2003/113704, U.S. Pat. No. 6,951,713, U.S. Pat. No. 6,709,810, WO 0191775, and U.S. Pat. No. 6,420,570, which are hereby fully incorporated by reference.
In an embodiment, the RBC can be processed using techniques well known in the art, e.g., the storage method can include contacting the RBC with a rejuvenation solution, such as pyruvate-inosine-phosphate-adenine solution (PIPA), irradiating the RBC, and the like.
In an embodiment, the RBC storage method can include gas exchanging the RBC to add or remove oxygen, carbon dioxide or a combination thereof. Additionally or alternatively, the RBC storage method can include dialysis to remove waste products from the RBC.
In an embodiment, the method may include agitating a medium such as plasma comprising the RBC, for example, pumping the medium comprising the RBC. In an embodiment, the RBC medium is passed through an electromagnetic stimulation zone.
The RBC storage method in embodiments can include controlling the temperature of the RBC between 1 and 6° C., or between about 30 and about 40° C.
The RBC storage method in one embodiment can be used to store the RBC in whole blood, optionally with an additive, for a period of time in excess of 35 days. The RBC storage method in another embodiment is used to store the RBC for a period of time in excess of 45 days. In other embodiments, the RBC storage method is effective such that the RBC and/or the storage media comprise more than 84% viable cells (as determined 24 hours post transfusion) following storage for 42 days, a pH greater than 6.98 following storage for 42 days, an ATP content greater than 86 percent of original ATP content at 21 days of storage, an ATP content greater than 60 percent of original ATP content at 42 days of storage, a 2,3-biphosphoglycerate (BPG) content greater than 44 percent of original BPG content at 21 days of storage, a BPG content greater than 10 percent of original BPG content at 42 days of storage, a plasma potassium concentration less than 21 mmol/L at 21 days of storage, a plasma potassium concentration less than 45 mmol/L at 42 days of storage, a plasma hemoglobin concentration less than 191 ng/L at 21 days of storage, a plasma hemoglobin concentration less than 386 ng/L at 42 days of storage, or any combination thereof.
In another embodiment, apparatus for storing red blood cells (RBC) comprises a storage container housing RBC in storage media and an electromagnetic stimulation zone to improve viability of the RBC.
In an embodiment, the RBC storage apparatus comprises an electric source to pass an electric current through the storage media, and the electric source can if desired include a controller to provide an amperage, voltage, wave form or a combination thereof corresponding to a cardiac cycle for the species of RBC. In embodiments, the electric source provides direct current or alternating current. The electric source in embodiments can include a controller to pulse the current at a frequency from 0.001 to 10 Hz; and/or to provide the current at a voltage potential between from 1 to 1000 millivolts.
In another embodiment, the RBC storage apparatus can additionally or alternatively comprise a magnetic field generator to apply a magnetic field to the RBC. In embodiments, the magnetic field comprises a static magnetic field or an oscillating magnetic field. The magnetic field can be either a homogenous magnetic field or a heterogeneous magnetic field. In exemplary embodiments, the magnetic field is within a range of from about 0.5 to about 500 Gauss or within a range of from about 10 to about 100 Gauss. The magnetic field generator in one example comprises a controller to pulse the magnetic field at a frequency from 0.001 to 10 Hz.
In the RBC storage apparatus according to one embodiment, the electromagnetic stimulation zone is disposed to apply the electromagnetic stimulation to the RBC just prior to or during transfusion into the recipient.
In one embodiment, the RBC storage media comprises whole blood and in a further embodiment comprises preservative solution such as, for example, citrate-potassium-dextrose solution (CPD) or citrate-potassium-dextrose-adenine solution (CPDA).
In one embodiment, the RBC storage apparatus comprises RBC separated from whole blood, and in a further embodiment comprises preservative solution such as, for example, adenine-saline solution (AS).
In an additional or alternative embodiment of the apparatus, the storage media can further comprise an added anticoagulant, pH buffer, nutrient, preservative, pathogen inactivator or combination thereof.
In an additional or alternative embodiment of the apparatus, the storage media further comprises an added rejuvenation solution.
The RBC storage apparatus in one embodiment can further comprise a gas exchange zone to add to the RBC or remove from the RBC oxygen, carbon dioxide or a combination thereof. In another embodiment, the RBC storage apparatus can further comprise a dialysis zone to remove waste products from the RBC.
In an additional or alternative embodiment, the RBC storage apparatus can comprise a shear zone to agitate the storage media comprising the RBC. In an embodiment, the RBC storage apparatus can include a pump to pump the storage media through an RBC flow circuit. For example, the RBC flow circuit can include the zone of electromagnetic stimulation.
In additional or alternative embodiments of the apparatus, a temperature control circuit is provided to maintain the temperature of the RBC, for example, between 1 and 6° C., or between about 30 and about 40° C.
In one embodiment, the electrical current or magnetic field applied to the RBC corresponds to the current or field applied to blood by the heart, either in a healthy heart or in the specific transfusion recipient, for example, a frequency and duration within 50% (i.e., 0.5 to 1.5 times the natural frequency or duration) or within 25% (i.e., 0.75 to 1.25 times the natural frequency or duration) of the electrical currents or fields ordinarily applied to blood from the atrioventricular node as it passes through the heart. In another embodiment, the strength of the current or field applied to the RBC is greater than that naturally applied in the right or left ventricle or right or left atrium, for example, 25, 50 or 100% greater, or from about twice to about 10 times greater, but not too great as to damage or injure the RBC, e.g. to avoid rouleaux. In one embodiment, the stored blood is periodically or continuously electrified or magnetized with a current and/or field effective to extend the life of the stored RBC. In other embodiments, the current or field is applied periodically to preserve the RBC, for example, from 1 to 5 seconds every 1 to 60 minutes or every 2 to 10 minutes, or from 30 seconds to 2 or 5 minutes every 1 to 12 hours, or for any duration and periodicity effective to improve the preservation and/or quality of the stored RBC. In an embodiment the electrical current and/or field are effective to inhibit charge depletion of the surface of the RBC, and in a further embodiment the electrical current and/or field are effective to maintain the magnetization levels of the heme irons in the RBC.
Thus, a patient can bank blood for autologous transfusion further in advance of surgery than is possible with conventional blood storage techniques, allowing the patient to fully recover from the blood loss. Further, the banked blood can be stored with a greater level of preservation or quality, which in one embodiment can be seen in the maintenance of uniform polarity of the RBC external surfaces. In other embodiments, the RBC have improved parameters indicative of viability, relative to conventional blood storage and preservation techniques, e.g., an increased proportion of viable cells (as determined 24 hours post transfusion) following storage, less pH loss or variation following storage, a greater ATP content greater relative to the original ATP content at collection, a greater 2,3-biphosphoglycerate (BPG) content relative to the original BPG content at storage, a lower plasma potassium concentration, a lower plasma hemoglobin concentration, or any combination thereof.
In one embodiment, the electromagnetic stimulation is applied to the blood as it is being transfused into the recipient, or just prior to transfusion, or for a period of time prior to transfusion to improve the RBC viability, e.g., for 6 to 24 hours prior to transfusion. For example, the current or field can be supplied to the transfusion container via electrodes and/or an external charging coil, which is activated during the transfusion, or in an embodiment before the transfusion for a duration effective to improve the external or surface polarity of the RBC, for example, 5 to 10 minutes. Where the RBC are treated for a sufficient duration prior to transfusion, the treatment can be continued at the same or a different, higher or lower current or field strength.
The blood storage bags 10, 30 shown in
In one embodiment, the blood bags 10, 30 shown in
In another embodiment, as illustrated in
The flow circulation circuit 42 comprises tubing 52 or other flow conduit and at least one pump 54 to continuously or periodically circulate the blood during storage. In an embodiment, the pump 54 comprises a magnetically shielded flow path in order to avoid or minimize exposure of the RBC to magnetic fields employed in the pump 54, especially static magnetic fields. Magnetically shielded pumps are disclosed in my copending applications U.S. Ser. No. 12/433,566 filed Apr. 30, 2009, U.S. 61/409,838 filed Nov. 3, 2010, and U.S. 61/415,561 filed Nov. 19, 2010, which are hereby fully incorporated herein by reference. The pump 54 preferably provides pressures similar to those in the cardiovascular system of the animal from which the blood is taken, e.g., 8 to 21.3 or 32 kPa (60 to 160 or 240 mm Hg) in the case of human blood, to simulate biological conditions and avoid damaging the RBC by excessive fluid pressure.
The flow circuit 42 may include one or more of an electromagnetic stimulation unit 56, respiration unit 58, dialysis unit 60, or any combination thereof. The magnetic stimulation unit can include electrodes to apply a current to blood flowing through the unit 56, an electromagnetic field generator to apply a magnetic field to the blood flowing through the unit 56, or both. In an embodiment, the electromagnetic stimulation unit 56 is integrated with the pump 54 to electromagnetically stimulate the blood in the blood flow path through the pump 54/unit 56, for example, wherein the magnetic field(s) in the stator and/or rotor of the pump 54 also function to provide the appropriate electromagnetic stimulation of the RBC.
In one embodiment, the electromagnetic stimulation unit 56 can provide small parallel flow channels with a diameter on the same order of magnitude as that of an RBC or capillary in the animal from which the blood was obtained, e.g. within 100 to 200%, preferably from 105 to 150% of the mean RBC diameter, or from 50 to 200% of the mean capillary diameter. For example, the simulated capillaries can have a cross sectional diameter of 5 to 20 microns or 8 to 15 microns. If desired, unit 56 can include appropriate supply and return manifolds to distribute the RBC flow through a plurality of the microchannels. The channels can be formed, for example, by placing grooves in a face of an inert plastic plate, sheet, film or block or other suitable material, and then securing the face to another face which can also be grooved. Where the grooves are semicircular in cross section and match with a similar groove in the opposite face, a circular channel will be formed; or where the opposite face is flat or planar the channel will be semicircular. Other shapes may be used, but circular cross sections matching the animal's capillary size and configuration are preferred. The number of channels should be sufficient to provide the total desired flow area, e.g., within 50 to 200% of the total cross sectional flow area in the tubing 52, 64. The length of the channels is not critical, although in general they are as short as possible to minimize pressure drop and hydraulic damage of the RBC as they “squeeze” through the capillary-mimicking channels, e.g., 0.5 to 5 cm.
In one embodiment the electromagnetic stimulation unit 56 also includes at least one electromagnetic field generator, which can be a degaussing (alternating) magnetic field, a static or step-pulsed deoxygenating field (magnetic north oriented toward the RBC or a cathodic electrical field), or an oxygenating field (magnetic south oriented toward the RBC or an anodic electrical field), or any combination thereof.
In one embodiment, a first generator is provided to simulate electrobiological intracapillary deoxygenation in tissue and a second generator is provided downstream in series to simulate electrobiological intracapillary oxygenation in the lungs. In one embodiment, oxygen can be supplied and/or taken off via a gas permeable membrane in contact with the RBC in the microchannels just described, in the downstream respiration unit 58, or in the storage bag 40. Additionally or alternatively, if desired, carbon dioxide can be supplied and/or taken off via the same or different gas permeable membranes.
In another embodiment, an electrical current similar in voltage and current to that normally supplied at the atrioventricular node can be applied through the blood to and away from the oxygenator. In one embodiment the mild current is applied from an upstream electrode, to an electrode adjacent the oxygenator; in another embodiment from a downstream electrode, to the oxygenator electrode; and in another embodiment, the current is applied from both of the upstream and downstream electrodes to the common oxygenator electrode. In one embodiment, the current from the upstream and/or downstream electrodes is pulsed in a pattern similar to that of the atrioventricular node, and in another embodiment, the downstream electrode is pulsed approximately 0.02 seconds after the upstream electrode, corresponding to the current flow and pattern of the in vivo current from the atrioventricular node to the blood flowing between the heart and to/from the pulmonary capillaries.
In one embodiment, the current, electromagnetic field or combination thereof generated in the unit 56 is effective to inhibit rouleaux aggregation and/or induce rouleaux disaggregation in the RBC.
The respiration unit 58 can be or include, for example, a gas exchange unit to maintain desired levels of respiration gases, e.g., a membrane oxygenator to add and/or remove carbon dioxide and/or oxygen, to maintain oxygenation and carbon dioxide levels. Membrane oxygenators are well known for use in extracorporeal membrane oxygenation (ECMO) devices. In one embodiment the respiration unit 58 can be integrated with the electromagnetic stimulation unit 56, e.g., to provide electromagnetic stimulation during or in conjunction with gas exchange. For example, the electromagnetic stimulation (type, magnitude, frequency, polarity) associated with oxygen uptake and/or carbon dioxide release can mimic that which is biologically present in the air sac capillaries in the lungs, or the electromagnetic stimulation (type, magnitude, frequency, polarity) associated with oxygen release and/or carbon dioxide uptake can mimic that found in the tissues or organs other than the lungs. In one embodiment, the respiration unit 58 can include subunits in series to release oxygen/absorb carbon dioxide in a first subunit and to absorb oxygen/release carbon dioxide in the second subunit, as described above. In an embodiment, the RBC in return line 64 and blood bag 40 are more or less fully oxygenated, e.g. an oximetry of 98-100%.
Dialysis unit 60 is optional and can be applied continuously to remove waste components formed by the biological activity of the RBC, especially at normal biological temperatures. Dialysis is a well known procedure for patient's with no or impaired renal function. If desired, the blood can be supplemented with nutrients such as glucose or a slow release source of glucose can be added at the initial collection or processing of the blood or RBC in preparation for storage.
If desired, a side stream processing unit 62 can be provided in the return tubing 64. The unit 62 can include any type of hematological processing or testing equipment, or provide a sampling port for withdrawing specimens for testing or analysis. In one embodiment, the unit 62 includes an organ perfusion unit for maintaining the viability of the organ for transplant.
In an embodiment, the storage device can comprise two of the storage bags 40 to store oxygenated-state RBC and deoxygenated-state RBC, respectively. The blood under storage can be alternatingly pumped between the two bags in a first cycle to deoxygenate the RBC and in a second cycle to oxygenate the blood. The oxygenation and deoxygenation cycles can be provided in separate lines which are continuously operated in opposite directions more or less maintaining a constant blood volume in each storage container, or alternatively, the blood flow can be reversed in batch operations wherein the processing is alternated between batches between oxygenation and deoxygenation cycles. In one embodiment, the blood within the storage system can be pumped at a space velocity from 50% to 200% of the biological space velocity, e.g., from about 1 volume per 30 seconds to 1 volume per 2 minutes.
By repeatedly cycling the RBC through oxygenating and deoxygenating steps with similar biological hydrodynamic conditions, the electromagnetic health of the RBC can be viably maintained in storage up to about the same period of time as the RBC survives in vivo, or longer. To the extent the viability of RBC in vivo is a function of hydrodynamic conditions (where bumping and friction slowly degrade the RBC), the viability in storage can theoretically be further improved relative to biological conditions by providing comparatively improved hydrodynamic conditions, i.e., less bumping or friction by providing smooth walls, large radii turns, gradual diameter changes, elimination of obstructions and tortuous flow paths, maintaining laminar flow conditions, etc.
In one embodiment, the tubing in the flow circuit 102 of
The magnets 84, 84′ in one embodiment exert a magnetic field onto the red blood cells 80, 80′, preferably of a like polarity with respect to the surface polarity of the erythrocytes 80, 80′. In one embodiment, the dipole orientation of the magnets 84, 84′ is the same as that of the surface of the red blood cell 80, 80′ so that there is a repulsion of the red blood cell 80, 80′ away from the inner surface of the tubing wall 82, 82′. For example, in
In one embodiment, especially at surfaces in contact with oxygenated blood, the magnets 84 can have a “mild” magnetic field strength which is similar to that at the surface of normal erythrocytes. In this embodiment, the idea is to control the red blood cells 80 from sticking together or to the exposed surfaces of the machine, but the field strength should not be so great as to induce oxygen release from the erythrocytes. A mild magnetic field can be attenuated in one embodiment by providing a relatively large flow cross section, e.g., 1-25 mm inside diameter, so that the magnets 80 exert only an extremely minor field at the centerline or axis of the flow passage 102. In one embodiment, the magnets 84 are provided at the oxygenator membranes in unit 106, which may also optionally be heparinized as is known in the art.
In another embodiment with reference to
Accordingly, the invention provides the following embodiments:
All numbers expressing quantities of ingredients, reaction conditions, and so forth in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches. Also, where a range is given, even if the term “between” is used, the ranges defined include the stated endpoints.
For all patents, applications, or other reference cited herein, it should be understood that such documents are incorporated by reference in their entirety for all purposes, as well as for any specifically recited proposition. Where any conflict exists between a document incorporated by reference and the present application, this application will dominate.
While various embodiments have been illustrated and described above, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the present disclosure. It is, therefore, intended that the scope of the present disclosure be determined from the following claims and equivalents thereof.
This application is a nonprovisional of U.S. 61/263,450 filed Nov. 23, 2009, a nonprovisional of U.S. 61/409,838 filed Nov. 3, 2010, and related to U.S. Ser. No. 12/433,566 filed Apr. 30, 2009.
| Number | Date | Country | |
|---|---|---|---|
| 61263450 | Nov 2009 | US | |
| 61409838 | Nov 2010 | US |
