Oxygen reduction disposable kit, device and method of use thereof

Abstract

Oxygen-Depleting Single-Use Kits, Devices, and Methods of Using Them. This disclosure relates to oxygen-depleting single-use kits (ORDKits), devices, and methods for improved whole blood and blood component preservation. The improved devices and methods for collecting blood and blood components provide whole blood and blood components with reduced oxygen levels. The devices and methods provide rapid preparation of deoxygenated blood and blood components for storage, which improves the overall quality of transfusion blood and improves patient health outcomes.

Description

[0001] This application is a divisional application of Chinese patent application No. 201680023315.5, entitled “Oxygen Reduction Disposable Kit, Device and Method of Use Thereof”, which is a PCT international patent application PCT / US2016 / 021794 filed on March 10, 2016, which entered the Chinese national phase.

[0002] Cross-references to related applications

[0003] This application claims the benefit of U.S. Provisional Application No. 62 / 131,130, filed March 10, 2015, which is incorporated herein by reference. Technical Field

[0004] This disclosure relates to oxygen reduction disposable kits (ORDKits), devices, and methods for improved whole blood and blood component preservation. More specifically, this disclosure relates to improved devices and methods for collecting blood and blood components to provide whole blood and blood components with reduced oxygen levels. The methods, devices, and kits of this disclosure provide improved quality of blood and blood components for transfusion, as well as improved patient safety and outcomes. Background Technology

[0005] The supply of liquid blood and blood components is currently limited by the storage systems used in routine blood storage practices. Using current systems, stored blood, as a compressed blood cell product, expires after approximately 42 days of refrigeration at temperatures above freezing (i.e., 4°C). For example, the World Health Organization (WHO) estimates that more than 100 million units of blood are collected and stored globally each year. According to the American Association of Blood Banks, 13.6 million units of red blood cells (RBCs) were collected in the United States alone in 2013. During refrigerated storage, RBCs gradually deteriorate due to storage lesions. When transfused within the current 6-week limit, stored RBCs exhibit lower quality and potential toxicity, which can manifest as side effects of transfusion therapy. Among the observed storage lesions are altered biochemical and physical parameters associated with stored red blood cells. Examples of these alterations include parameters measured in vitro, such as decreased levels of metabolites (ATP and 2,3-diphosphoglycerate (2,3-DPG)), increased levels of free cellular iron, hemolysis, increased microparticle levels, decreased surface area, increased acanthocytosis, phosphatidylserine exposure, and decreased deformability. Expired blood cannot be used and must be discarded because it may harm the final recipient. These and other reasons limit the amount of readily available, high-quality blood required for transfusion.

[0006] When routinely stored, stored blood undergoes a continuous deterioration associated with hemolysis, hemoglobin degradation, and decreased ATP and 2,3-DPG concentrations. The effects of this continuous deterioration during storage manifest as, for example, reduced recovery within 24 hours when transfused to a patient. Prolonged storage of red blood cells under routine conditions leads to deterioration, with up to 25% being removed from the recipient's body shortly after transfusion. Non-viable RBCs cause iron overload in patients receiving long-term transfusions. Due to 2,3-DPG depletion, hemoglobin in RBCs does not efficiently release oxygen into tissues. Due to loss of deformability, RBCs cannot enter and perfuse the capillary bed. Storage complications in transfused blood can lead to failure of major organs such as the lungs, heart, kidneys, liver, and central nervous system. Storage complications in transfused blood are associated with increased morbidity.

[0007] Transfusing red blood cells stored for a longer period under routine conditions, compared to transfusing “fresher” red blood cells, can lead to higher morbidity and longer hospital stays. Specifically, red blood cells stored for more than 3 weeks result in higher morbidity and longer hospital stays compared to fresher red blood cells. For example, negative clinical outcomes have occurred during cardiac surgery when “older” blood is used; multi-organ failure in surgical patients is associated with the age of the transfused red blood cells; older units are associated with increased mortality from severe sepsis; failure to improve O2 utilization is attributed to reduced 2,3-DPG; and decreased cardiac index is associated with increased blood viscosity.

[0008] Besides the immediate removal of certain RBCs by the recipient, the consequences of RBC storage disorders include: (i) ATP depletion (loss of the ability of RBCs to dilate capillary arteries before dilation); (ii) 2,3-DPG depletion; (iii) accumulation of oxidative damage caused by reactive oxygen species (ROS) formed from the reaction of melanin with O2; and (iv) decreased RBC deformability and increased RBC viscosity, partly due to oxidative damage to the cell membrane and cytoskeleton. A small number of deformable RBCs are excluded from capillary channels, leading to decreased capillary occupancy and reduced tissue perfusion. Massive transfusions of cells with reduced deformability can also contribute to multiple organ failure by obstructing the capillary bed of organs. Following transfusion, 2,3-DPG is synthesized relatively rapidly in vivo, reaching approximately 50% of normal levels within 7 hours and approximately 95% within 2–3 days. However, because cells depleted of 2,3-DPG cannot immediately recover their levels, impaired O2 carrying capacity is detrimental to critically ill patients requiring immediate O2 delivery and tissue perfusion. Many reports emphasize the importance of RBCs with high oxygen-carrying capacity in such clinical situations.

[0009] Red blood cell (RBC) transfusion is a life-saving therapy designed to improve oxygenation of tissues and vital peripheral organs in patients with severe anemia. Most RBC units used for transfusion are stored for up to 42 days in oxygen-permeable PVC blood bags containing additive / preservative solutions at 1–6°C.

[0010] The storage of frozen blood is known in the art, but such frozen blood has limitations. For many years, frozen blood has been used by blood banks and the military for certain high-demand and rare blood types. However, frozen blood is difficult to handle. It must be thawed, and then the cryoprotectant must be gradually washed away, which is impractical for emergency situations. Once thawed, the blood must be used within 48 hours. Serebrennikov's U.S. Patent No. 6,413,713 relates to a method for storing blood at temperatures below 0°C.

[0011] U.S. Patent Nos. 4,769,318 to Hamasaki et al. and 4,880,786 to Sasakawa et al. relate to additive solutions for blood preservation and activation. U.S. Patent Nos. 5,624,794, 6,162,396, and 5,476,764 to Bitensky et al. relate to storing red blood cells under oxygen-consuming conditions. U.S. Patent No. 5,789,151 to Bitensky et al. relates to blood storage additive solutions. For example, Rejuvesol (available from CitraLab LLC, Braintree, MA) is added to the blood immediately after cold storage (i.e., 4°C) and just before transfusion, or before freezing (i.e., with glycerol at -80°C) for long-term storage. U.S. Patent No. 6,447,987 to Hess et al. relates to additive solutions for the cryopreservation of human red blood cells.

[0012] U.S. Patent No. 4,837,047 to Sato et al. relates to containers for long-term storage of blood to maintain good blood quality.

[0013] Traditional manual blood collection is performed by a trained phlebotomist using a blood collection kit, which includes at least a blood collection bag, a puncture needle, and tubing sufficient to connect the needle to the blood collection bag containing an anticoagulant. Typically, the blood collection bag also includes an anticoagulant solution, but the anticoagulant solution may optionally be supplied in a separate bag or container connected to the blood collection bag with suitable tubing. No component of current commercial systems provides or includes oxygen reduction.

[0014] Oxygen reduction from the blood needs to begin at collection time, prior to storage. To complete blood regeneration within existing infrastructure and the timeframes limited by current regulations, oxygen reduction needs to begin as early as possible, preferably at collection time before the temperature of the collected blood drops significantly. Summary of the Invention

[0015] This disclosure provides and includes an oxygen consumption device for consuming oxygen from blood prior to anaerobic storage, the oxygen consumption device comprising a substantially oxygen-impermeable external receptor, an internal collapsible blood container comprising one or more oxygen-impermeable chambers, and an oxygen adsorbent located within the external receptor.

[0016] This disclosure provides and includes an oxygen consumption device for consuming oxygen from whole blood prior to anaerobic storage, the oxygen consumption device comprising a substantially oxygen-impermeable external receiver, an internal collapsible blood container comprising one or more oxygen-impermeable chambers, and an oxygen adsorbent located within the external receiver.

[0017] This disclosure provides and includes an oxygen consumption device for consuming oxygen from compressed red blood cells prior to anaerobic storage, the oxygen consumption device comprising a substantially oxygen-impermeable external receiver, an internal collapsible blood container comprising one or more oxygen-impermeable chambers, and an oxygen adsorbent located within the external receiver.

[0018] This disclosure provides and includes a method for preparing blood for storage, the method comprising providing an oxygen-consuming device including a substantially oxygen-impermeable external receiver, an internal collapsible blood container enclosed within the external receiver, and an oxygen adsorbent located between the external receiver and the internal blood-compatible blood container; allowing blood to flow into the internal collapsible blood container of the oxygen-consuming device; and producing oxygen-depleted blood having an oxygen saturation of less than 20%.

[0019] This disclosure provides and includes a method for preparing blood for storage, the method comprising providing an oxygen-consuming device including a substantially oxygen-impermeable external receiver, an internal collapsible blood container enclosed within the external receiver, and an oxygen adsorbent located between the external receiver and the internal blood-compatible blood container; allowing blood to flow into the internal collapsible blood container of the oxygen-consuming device; and producing oxygen-depleted blood having an oxygen saturation of less than 10%.

[0020] This disclosure provides and includes a blood storage device for storing oxygen-depleted blood, the blood storage device comprising a substantially oxygen-impermeable external receiver; an internal collapsible blood container including positioning features adapted to align the collapsible blood container within the geometry of the external receiver; at least one inlet including a tube connected to the collapsible blood container and an adhesive to the external receiver, wherein the adhesive to the external receiver is substantially oxygen-impermeable; and an oxygen adsorbent located within the external receiver.

[0021] This disclosure provides and includes an oxygen consumption device 10 for consuming oxygen from blood prior to anaerobic storage, comprising a substantially oxygen-impermeable external receiver 101; an oxygen indicator 206; a spacer material 110; and approximately 80 grams of oxygen adsorbent 103 located between the external receiver 101 and a 15 μm to 200 μm thick siloxane collapsible blood container 102.

[0022] This disclosure provides and includes an oxygen-consuming device 10 for consuming oxygen from blood prior to anaerobic storage, comprising a substantially oxygen-impermeable external receiver 101; an oxygen indicator 206; a spacer material 110; and approximately 80 grams of oxygen adsorbent 103 located between the external receiver 101 and a collapsible blood container 102 made of PVDF having a pore size of 0.2 μm. This disclosure provides a method for preparing blood for storage, the method comprising: providing the oxygen-consuming device 10 and allowing blood to flow into an internal collapsible blood container 102; agitating the oxygen-consuming device 10 for up to 3 hours to produce oxygen-depleted blood with an oxygen saturation of less than 20%; and transferring the oxygen-depleted blood to a blood storage device 20. The method also provides the production of oxygen-depleted blood with an oxygen saturation of less than 20% within 8 hours of collection from a donor. In another embodiment, agitation is nutation.

[0023] This disclosure provides and includes a method for reducing oxygen from whole blood or its components, the method comprising placing whole blood or its components in a device 20 comprising an adsorbent 207 having an absorption rate of at least 1.86 cubic centimeters / gram of adsorbent / hour (vv·g). -1 ·Hour -1 The blood-filled device 20 is incubated at ambient temperature for up to four hours while being agitated at least once per second by translating at least 3 cm; the blood-filled device 20 is then transferred to a storage temperature of 4°C to 6°C. Alternatively, the blood-filled device 20 is stored at a temperature of 4°C to 6°C for up to 42 days. Attached Figure Description

[0024] Some aspects of this disclosure are described herein by way of example only and with reference to the accompanying drawings. Referring now specifically to the drawings, it should be emphasized that the details shown are by way of example and are for the purpose of illustrative discussion of embodiments of this disclosure. In this respect, the description using the drawings will make it apparent to those skilled in the art how aspects of this disclosure can be implemented.

[0025] Figure 1A -C illustrates an exemplary embodiment of an oxygen consumption device having two compartments arranged side by side, according to the present disclosure.

[0026] Figure 2A and 2B An exemplary embodiment of an oxygen consumption device having three compartments arranged side by side, according to the present disclosure, is shown.

[0027] Figure 3A and 3B An exemplary embodiment of an anaerobic storage bag according to this disclosure is shown.

[0028] Figure 4A and 4B An exemplary embodiment of a disposable oxygen reduction storage system according to the present disclosure is shown, which has a blood consumption device and an anaerobic storage bag, each having two or three compartments.

[0029] Figure 5 This is a graph showing the reduction of SO2 in an exemplary oxygen-consuming device according to the method of this disclosure.

[0030] Figure 6A and 6B An exemplary embodiment of an anaerobic storage bag according to this disclosure is shown.

[0031] Figure 7 An exemplary embodiment of the bonding layer 105 connecting membranes 113 and 114 in a two-step process according to the present disclosure is shown.

[0032] Figure 8A and 8B An exemplary embodiment of spacer 110 according to the present disclosure is shown, the spacer 110 including an inner mesh 117 co-extruded with an adhesive mesh 118 and attached to a membrane 113 (114).

[0033] Figure 9A and 9B An exemplary embodiment of an anaerobic storage bag according to the present disclosure is shown, the anaerobic storage bag having a bonding layer 105 (9A) connecting membranes 113 and 114 and a bonding layer 105 applied to membranes 113 and 114 to provide a seal 108, wherein the bonding layer 105 extends beyond the seal 108 by a distance 109 (9B).

[0034] Figures 10A to 10D An exemplary embodiment of the bonding layer 105 is shown, which has a geometric feature 121 according to the present disclosure and also includes a hybrid structure 109 as shown in 10C and 10D.

[0035] Figure 11 An exemplary embodiment of a collapsible blood container according to the present disclosure is shown, having a spacer 110, a bonding layer 105, and a geometric feature 121.

[0036] Figure 12 This is a graph showing the reduction of SO2 in an exemplary oxygen-consuming device according to the method of this disclosure.

[0037] Figure 13 This is a graph showing the reduction of SO2 in an exemplary internal collapsible blood container 102 with various blood volumes according to the method of this disclosure.

[0038] Figure 14 This is a graph showing the reduction of SO2 in an exemplary oxygen-consuming device according to the method of this disclosure.

[0039] Figure 15 This is a graph showing the reduction of SO2 in exemplary oxygen-consuming devices with different surface areas according to the method of this disclosure.

[0040] Figure 16 This is a diagram illustrating the effect of spacer 110 on reducing SO2 in an exemplary oxygen-consuming device according to the present disclosure.

[0041] The corresponding reference characters consistently indicate the corresponding components in several views. The examples described herein illustrate several embodiments of the invention but should not be construed as limiting the scope of the invention in any way.

[0042] Given current technology, there is a need to improve the quality of blood and blood components (such as red blood cells to be stored) and extend the storage period of such blood and blood components before transfusion to help minimize transfusion-related morbidity. To comply with regulatory requirements and ensure reliability, the preparation and processing of red blood cells must be completed within a limited timeframe. Furthermore, methods for preparing oxygen-depleted blood and blood components must not introduce pathological changes, including but not limited to hemolysis. Finally, methods and apparatus compatible with existing anticoagulant and additive solutions are needed to produce blood and blood components of improved quality. Detailed Implementation

[0043] To meet such and other needs, this disclosure includes and provides apparatus and methods for preserving blood and blood components, wherein the preparation of oxygen-depleted blood and blood components is initiated during a donor collection phase.

[0044] Before explaining at least one aspect of this disclosure in detail, it should be understood that this disclosure is not necessarily limited to the application of the details set forth in the following description or illustrated by examples. This disclosure can have other aspects or can be practiced or carried out in various ways.

[0045] As used herein, the term "bag" refers to a collapsible container made of flexible material and includes pouches, tubes, and gusseted bags. As used herein and included in this disclosure, the term includes a folded bag having one, two, three, or more folds, and said folded bag being sealed or glued on one, two, three, or more sides. Bags can be prepared using a variety of techniques known in the art, including bonding sheets of one or more materials. Methods of bonding materials to form bags are known in the art. This disclosure also includes and provides containers prepared by injection molding and blow molding. Methods of preparing blow-molded containers and injection-molded containers are known in the art. A preferred type of blow-molded or injection-molded container is a flexible container that can be reduced in size for efficient packaging and transport while being able to expand to accommodate blood or blood components for deoxygenation. They can also be designed to conform to the volume of blood until they are fully expanded. As used throughout this disclosure, a bag is a form of collapsible container, and the two terms are used interchangeably throughout this disclosure.

[0046] As used herein, the term "foldable container" includes bags, containers, shells, tubes, pouches, pockets, receivers, and other devices capable of containing and retaining liquids or fluids. In some aspects, foldable containers can be manufactured by conventional means, such as injection molding or insert molding. In other aspects, foldable containers can be prepared from sheets of polymeric material bonded together using methods known in the art to prepare a container capable of accommodating a volume. Such foldable containers are well known in the art. See, for example, U.S. Patent 3,942,529 to Waage; U.S. Patent 4,131,200 to Rinfret; and U.S. Patent 5,382,526 to Gajewski et al. Suitable methods for bonding polymeric materials to prepare foldable containers according to this disclosure include thermal welding, ultrasonic welding, radio frequency (RF) welding, and solvent welding. In some aspects, a variety of bonding methods can be used to prepare foldable containers according to this disclosure. Foldable containers according to this disclosure include shells having one or more pleats, folds, diaphragms, bubbles, and gussets. Methods for fabricating foldable containers are known in the art. See, for example, U.S. Patent 3,361,041 to Grob; U.S. Patent 4,731,978 to Martensson; U.S. Patent 4,998,990 to Richter et al.; and U.S. Patent 4,262,581 to Ferrell. This disclosure also includes and provides containers having a combination of flexible and non-flexible components, wherein the flexible components allow volume to expand by means of, for example, pleats, folds, or gussets, and other similar geometric features in the packaging shape, while the non-flexible components provide rigidity and geometric definition for the container. Methods and designs for fabricating foldable containers with flexible and non-flexible components are known in the art, such as those described by Randall in U.S. Patent 6,164,821 and by LaFleur in U.S. Patent 5,328,268.

[0047] As used in this article, the term "about" means ±10%.

[0048] The terms “comprises,” “comprising,” “includes,” “including,” “having,” and their cognates mean “including but not limited to.”

[0049] The term “composed of” means “including and limited to”.

[0050] The term "consistently made of" means that a composition, method, or structure may include additional ingredients, steps, and / or components, but only if the additional ingredients, steps, and / or components do not substantially alter the essential and novel characteristics of the claimed composition, method, or structure.

[0051] Unless the context clearly indicates otherwise, as used herein, the singular forms “a / an” and “the” include plural objects. For example, the terms “a compound” or “at least one compound” can include multiple compounds, including mixtures thereof.

[0052] Throughout this application, various embodiments of this disclosure may be presented in a scope format. It should be understood that the scope format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of this disclosure. Therefore, a scope description should be considered to have all possible sub-scopes exactly disclosed, as well as individual numerical values ​​within those scopes. For example, a scope description such as “1 to 6” should be considered to have exactly disclosed sub-scopes such as “1 to 3”, “1 to 4”, “1 to 5”, “2 to 4”, “2 to 6”, “3 to 6”, etc., and individual numbers within those scopes, such as 1, 2, 3, 4, 5, and 6. This applies regardless of how wide the scope may be.

[0053] Whenever a range of values ​​is indicated in this document, it means that any referenced numerical value (fraction or integer) within the indicated range is included. The phrases “ranging / ranges between the first and second indicated numbers” and “ranging / ranges from the first indicated number to the second indicated number” are used interchangeably in this document and mean including the first and second indicated numbers and all fractions and integers between them.

[0054] As used herein, the term "method" refers to the manner, means, techniques, and procedures used to accomplish a given task, including but not limited to known manner, means, techniques, and procedures or manner, means, techniques, and procedures that practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine can readily develop from known manner, means, techniques, and procedures.

[0055] This disclosure provides and includes an oxygen consumption device 10 for consuming oxygen from blood, comprising a substantially oxygen-impermeable external receiver 101, an oxygen-impermeable internal collapsible blood container 102, and an oxygen adsorbent 103 located within the external receiver 101.

[0056] This disclosure also provides and includes an oxygen-consuming device 10 configured as a blood collection and oxygen-consuming device 10. The oxygen-consuming device configured to collect and reduce blood oxygen differs from the oxygen-consuming device 10 described throughout this specification in that the blood collection and oxygen-consuming device 10 also includes an anticoagulant to prevent coagulation of whole blood during the collection process. In some aspects, an anticoagulant solution is provided in the blood collection and oxygen-consuming device 10. Therefore, the included anticoagulant solution is also an anticoagulant solution for oxygen consumption. In alternative embodiments, an anticoagulant solution may be included separately as an oxygen-consuming solution or as a solution containing oxygen. The blood collection and oxygen-consuming device 10 is intended for use with whole blood collected from a donor. As used throughout this disclosure, the oxygen-consuming device 10 includes and provides the blood collection and oxygen-consuming device 10. These two terms are used interchangeably.

[0057] As used herein, the external receiver is made of a material that is substantially impermeable to oxygen and optionally impermeable to carbon dioxide. In some respects, the external receiver 101 is made of a flexible membrane material. In other respects, the external receiver 101 is made of a rigid or non-flexible membrane material.

[0058] This disclosure provides and includes a substantially oxygen-impermeable external receiver 101. As used herein, the substantially oxygen-impermeable external receiver 101 is sufficiently impermeable to oxygen to allow the oxygen inside the receiver to not exceed 10 cc after a 3-month period, and more preferably not exceed 5 cc after 6 months. As used herein, the term substantially oxygen-impermeable (SIO) means that the materials and compositions provide a barrier layer to prevent oxygen from passing through from one side of the barrier layer to the other, which is sufficient to prevent a significant increase in oxygen partial pressure.

[0059] It is worth noting that few materials provide complete impermeability, and even highly impermeable materials can be compromised when the external receiver 101 is joined, welded, folded, or otherwise assembled. As will be discussed below, the oxygen consumption device 10 may also incorporate one or more inlets / outlets 30, which include a tube 301 and an adhesive 302 to the external receiver 101 (or external receiver 201 hereinafter). The external receiver 101 must also be designed to accommodate volume changes in the internal collapsible blood container 102. Therefore, special attention must be paid to incorporating specific design elements and manufacturing methods to ensure the integrity of the impermeable barrier layer.

[0060] This disclosure also provides and includes an external receiver 101 that is substantially impermeable to oxygen, having an oxygen permeability of less than about 1.0 cc oxygen / m² / day. In some respects, membranes suitable for preparing the external receivers and other elements of this disclosure are characterized by a Barrer value of less than about 0.140.

[0061] Materials and methods for preparing the external receiver 101 are known in the art. See, for example, U.S. Patent 7,041,800 to Gawryl et al., U.S. Patent 6,007,529 to Gustafsson et al., and U.S. Patent Application Publication No. 2013 / 0327677 to McDorman, each of which is incorporated herein by reference in its entirety. Impermeable materials are conventionally used in the art, and any suitable material may be used. In the case of molded polymers, additives are conventionally added to enhance oxygen (and CO2) barrier properties. See, for example, U.S. Patent 4,837,047 to Sato et al. For example, U.S. Patent 7,431,995 to Smith et al. describes an oxygen- and carbon dioxide-impermeable receiver composed of layers of an ethylene vinyl alcohol copolymer and a modified ethylene vinyl acetate copolymer that impermeable to oxygen and carbon dioxide. In another respect, the external receiver 101 is impermeable to oxygen and carbon dioxide.

[0062] In some respects, a substantially oxygen-impermeable membrane can be a laminated membrane. In one respect, a substantially oxygen-impermeable laminated membrane is a laminated foil. The membrane material can be a polymer or a foil material or a combination of foil and polymer in a multilayer construction. In another respect, the laminated membrane can be a polyester film laminated with aluminum. Examples of suitable substantially oxygen-impermeable aluminum laminated membranes (also known as laminated foils) are known in the art. For example, U.S. Patent 4,798,728 to Sugisawa discloses aluminum laminated foils of nylon, polyethylene, polyester, polypropylene, and vinylidene chloride. Other laminated membranes are known in the art. For example, U.S. Patent 7,713,614 to Chow et al. discloses a substantially oxygen-impermeable multilayer container comprising an ethylene-vinyl alcohol copolymer (EVOH) resin. In one respect, the external receiver 101 can be a barrier bag constructed by heat-sealing three or four sides. The bag is constructed of multiple layers and includes materials that provide enhanced O2 and CO2 barrier properties. These materials include those with an oxygen permeability of 0.01 cc / 100 inches. 2 / 24-hour Rollprint V2 membrane, oxygen permeability 0.004cc / 100 inches 2 / 24-hour Rollprint The X-ray membrane has an oxygen permeability of 0.0008 cc / 100 inches. 2 24 hours Z-film (Rollprint Packaging Products, Addison, IL). Other manufacturers produce products with similar oxygen permeability, such as Renolit Solmed. Membrane (American Renolit Corp., City of Commerce, CA). Examples of suitable aluminum laminated films (also known as laminated foils) that are essentially impermeable to oxygen are available from Protective Packaging Corp. (Carrollton, TX).

[0063] Another suitable approach for preparing SIO materials includes multilayer graphene films produced by the mild chemical reduction of graphene oxide laminates with hydroiodic acid and ascorbic acid. See Su et al., “Impermeable barrier films and protective coatings based on reduced graphene oxide,” Nature Communications 5, article number: 4843 (2014), which is incorporated herein by reference in its entirety. Nanoparticles that enhance oxygen barrier properties are also known in the art, such as multilayer barrier laminates provided by Tera-Barrier (Tera-Barrier Films Pte, Ltd, The Aries, Singapore) and described by Rick Lingle in Packaging Digest Magazine, August 12, 2014.

[0064] In aspects according to this disclosure, the external receiver 101 may be made of a gas-impermeable plastic. In one embodiment, the gas-impermeable plastic may be a laminate. In some embodiments, the laminate may be a transparent barrier film, such as a nylon polymer. In embodiments, the laminate may be a polyester film. In one embodiment, the laminate may be... In some embodiments, the laminate may be a metallized film. In one embodiment, the metallized film may be coated with aluminum. In another embodiment, the coating may be aluminum oxide. In yet another embodiment, the coating may be an ethylene vinyl alcohol copolymer (EVOH) laminated between layers of low-density polyethylene (LDPE).

[0065] The external receiver 101 of this disclosure may be formed from one or more components made of a gas-impermeable material comprising plastic or other durable, lightweight materials. In some embodiments, the housing may be formed from more than one material. In one embodiment, the external receiver 101 may be formed from one material and coated with a gas-impermeable material to prepare a gas-impermeable housing. In one embodiment, the rigid or flexible external receiver 101 may be made from an injection-molded plastic. In embodiments according to this disclosure, the plastic may be selected from polystyrene, polyvinyl chloride, or nylon. In one embodiment, the material of the external receiver 101 may be selected from the group consisting of: polyester (PES), polyethylene terephthalate (PET), polyethylene (PE), high-density polyethylene (HDPE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), low-density polyethylene (LDPE), polypropylene (PP), polystyrene (PS), high-impact polystyrene (HIPS), polyamide (PA) (e.g., nylon), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polycarbonate / acrylonitrile butadiene styrene (PC / ABS), polyurethane (PU), melamine formaldehyde (MF), plastic starch material, phenolic resin (PF), polyetheretherketone (PEEK), polyetherimide (PEI) (Ultem), polylactic acid (PLA), polymethyl methacrylate (PMMA), polytetrafluoroethylene (PTFE), urea-formaldehyde, and ethylene vinyl alcohol copolymer (EVOH). In some embodiments, the external receiver 101 may be polyethylene. In some embodiments, the polyethylene external receiver 101 may include one or more polyethylene components welded together. In some respects, the external receiver is composed of a multilayer film having a polyethylene outer layer, a polyester inner layer, and an alumina barrier layer dispersed between the inner and outer layers, for example, with an oxygen permeability of 0.0008 cc / 100 inches. 2 24 hours Z film (Rollprint Packaging Products, Addison, IL).

[0066] This disclosure provides and includes an external receiver 101 made of a membrane and an internal collapsible blood container 102 made of a membrane. As used herein, membrane generally refers to the material used to make the internal collapsible blood container 102, while membrane conventionally refers to the material used to make the external receiver 101. Although it should be understood that for clarity, certain materials may be referred to as “membrane” by the manufacturer or generally as “membrane,” membranes are considered substantially impermeable unless otherwise specified. Membranes comprise one or more layers of material in the form of a sheet, which allows one or more substances to pass from one side of the sheet to the other. As used herein, membranes may also be made into tubes adapted to connect components of the oxygen consumption device 10 to a blood collection kit or to connect elements of the blood collection device, additive solution bags, leukopenia filters, and anaerobic storage bags. As used throughout, it should be understood that, depending on the application, the membranes of this disclosure may be formed as sheets or tubes. Also as previously provided, the membrane used to make the external receiver 101 is substantially oxygen-impermeable, while the internal collapsible blood container 102 is oxygen-impermeable. As used herein, the membrane can also be prepared as a tube adapted to connect components of the oxygen-consuming device 10 to a blood collection kit or to connect elements of the blood collection device, additive solution bag, leukopenia filter, and anaerobic storage bag. As used herein, the external receiver 101 includes all embodiments of 102 as further described in paragraphs

[00172] and

[00175] .

[0067] As used herein, the internal collapsible blood container 102 is permeable to oxygen. In some respects, the internal collapsible blood container 102 is permeable to both oxygen and carbon dioxide. In other respects, the internal collapsible blood container 102 is impermeable to oxygen but permeable to carbon dioxide.

[0068] This disclosure provides and includes the fabrication of an external receiver 101 using heat-sealing, blow molding, and injection molding techniques. Suitable materials for fabricating the external receiver 101 using heat-sealing, blow molding, and injection molding include PET, standard and multilayer polypropylene, polyethylene, polycarbonate, ABS, and other polymers known to those skilled in the art. Methods for fabricating blow-molded and injection-molded external receivers 101 are known in the art, for example, multilayer structures consisting of a barrier layer of ethylene vinyl alcohol (EVOH) or ethylene vinyl acetate (EVA) between two layers of polypropylene (PP), and said multilayer structures are provided by Kortec (Kortec, Inc., Rowley, MA) and are also described as in U.S. Patent 5,906,285 to Slat. Additives that enhance the oxygen and CO2 barrier properties of the polymer before molding or during its formulation or during assembly are known in the art. One example is multilayer polymer co-injection molding to obtain multilayer PET. This barrier resin is typically incorporated into both sides of the PET as an inner layer during the preform stage, thus making the PET both the liquid contact layer and the outer layer. As provided below, a suitable blow-molded or injection-molded outer receiver 101 is oxygen-impermeable. In some respects, a suitable heat-sealed, blow-molded, or injection-molded outer receiver 101 is substantially oxygen- and carbon dioxide-impermeable.

[0069] This disclosure provides and includes two types of materials for preparing permeable or substantially impermeable membranes. In one aspect, a permeable membrane according to this disclosure allows substances to pass through the material, specifically but not necessarily only oxygen. In some aspects, the membrane is selected to allow oxygen and carbon dioxide to pass through while preventing the passage of water, proteins, salts (e.g., plasma components), and cells (e.g., red blood cells, white blood cells, and platelets). The rate of passage through the material depends on one or more properties, including particle size, material phase (liquid or gas), hydrophilicity, hydrophobicity, or solubility. The rate or flux through the material also depends on the presence or absence of driving forces, such as differences in pressure (or partial pressure), temperature differences, or concentration differences between one side of the membrane and the other. The flux through the membrane is referred to as the membrane permeation flux. The membrane permeation flux of a substance through the membrane is inversely proportional to the membrane thickness.

[0070] The membrane permeation flux of a gas is defined as the volume of gas flowing through a unit area of ​​the membrane per unit time. The SI unit used is m³. 3 / m 2For gases and vapors, the volume depends largely on pressure and temperature. Therefore, the permeation flux of gases is often given according to standard temperature and pressure (STP), defined as 0°C and 1 atmosphere (1.0013 bar) (e.g., 273°K and 760 Torr). As mentioned above, the permeation rate depends on the driving force or difference between the two sides of the membrane, and this dependence is incorporated into the permeability coefficient P or simply the permeability.

[0071] Permeability (P) is defined as the permeable flux per unit membrane thickness per unit driving force. SI units for the permeability coefficient P are provided in Table 1. As in this disclosure, the common unit for gas separation is the barley, and it is also presented in Table 1. Term cm 3 Gas (STP) / cm 2 s refers to the volumetric transmembrane flux of the diffusing substance under standard conditions of 0°C and 1 atmosphere. The term cm refers to the membrane thickness, and cm-Hg refers to the driving force of the transmembrane partial pressure of the diffusing substance. Permeability must be determined experimentally.

[0072] Table 1: Permeability Units

[0073]

[0074] Membranes suitable for use in the methods and apparatus according to this disclosure include dense membranes, porous membranes, asymmetric membranes, and composite membranes. In some aspects, suitable membranes may be multilayer membranes. In other aspects, suitable membranes are prepared from inorganic materials. Dense membranes are membranes prepared from solid materials that do not have pores or voids. The material permeates the dense membrane through a process of dissolution and diffusion. Examples of dense membranes include siloxane membranes (polydimethylsiloxane or PDMS). This disclosure also includes and provides porous membranes having pores within a specific size range based on size exclusion separation. Examples of porous membranes suitable for use according to this disclosure include PVDF and polysulfone membranes.

[0075] This disclosure includes and provides composite membranes made of more than one material, often as a laminate, wherein a dense material is applied to a porous support layer. An example of a composite membrane suitable for use according to this disclosure is a GVHP hydrophobic PVDF with an EMD Millipore having a pore size of 1.0 μm or 0.22 μm.

[0076] Table 2: Permeability of fluoropolymers (100 μm thickness; 23°C)

[0077]

[0078]

[0079] This disclosure provides and includes an internally collapsible blood container 102 made of membrane 113, characterized primarily by its oxygen permeability. Unless otherwise specified, "substantially impermeable membrane" means a membrane that is substantially impermeable to oxygen. However, in some devices and methods, the membrane may also be characterized as permeable to or impermeable to carbon dioxide. For some applications, the membrane material is substantially impermeable to oxygen and provides a barrier layer against the introduction of oxygen into blood, blood components, or a blood collection kit consisting of multiple components. Such substantially impermeable membranes are generally used to prepare the external receivers of this disclosure. Suitable substantially impermeable membranes can also be used to prepare tubing for connection assemblies in devices and kits. A substantially impermeable membrane may comprise a single layer or may be a laminate or tube having two or more layers.

[0080] This disclosure also provides and includes a substantially oxygen-permeable membrane 113. The substantially oxygen-permeable membrane 113 is used in this disclosure for the fabrication of an internally collapsible blood container 102. In some aspects, the oxygen-permeable membrane 113 is also a biocompatible membrane that is approved and suitable for prolonged contact with blood to be transfused into a patient. Like substantially impermeable membranes, the substantially permeable membrane 113 may comprise a single layer or may comprise a laminated structure having two or more layers.

[0081] On the one hand, the oxygen permeability is greater than approximately 2.5 x 10⁻⁶. -9 cm 3 O2(STP) / (cm 2 s)*(cm Hg cm -1 An oxygen-permeable membrane 113 is used to prepare a collapsible blood container 102. On the other hand, the oxygen permeability is greater than about 5.0 x 10⁻⁶. -9 cm 3 O2(STP) / (cm 2 s)*(cm Hg cm -1 The oxygen-permeable membrane 113 is used to prepare the collapsible blood container 102. On another note, the oxygen permeability of the oxygen-permeable membrane 113 is greater than about 1.0 x 10⁻⁶. -8 cm 3 O2(STP) / (cm 2 s)*(cm Hg cm -1 In some aspects, the oxygen-permeable membrane 113 suitable for preparing the collapsible blood container 102 is characterized by a Barre value greater than about 25. In other aspects, the oxygen-permeable membrane 113 suitable for preparing the collapsible blood container 102 is characterized by a Barre value greater than about 50. In some other aspects, the oxygen-permeable membrane 113 suitable for preparing the collapsible blood container 102 is characterized by a Barre value greater than about 100.

[0082] On the one hand, the substantially oxygen-permeable membrane 113 can be a dense membrane made of a non-porous material. Examples of suitable materials with high oxygen permeability include siloxanes, polyolefins, epoxy resins, and polyesters. On the other hand, the substantially oxygen-permeable membrane can be a porous membrane made of an organic polymer. The substantially oxygen-permeable membrane 113 can be made of materials selected from the group consisting of: hydrophobic PVDF, nylon, cellulose esters, polysulfone, polyethersulfone, hydrophobic polypropylene, and polyacrylonitrile.

[0083] This disclosure provides and includes the preparation of a substantially oxygen-permeable membrane 113 not only by selecting materials but also by selecting and controlling the thickness. As provided above, permeability is proportional to the membrane thickness. Therefore, improved permeability can be achieved by reducing the membrane thickness. In some respects, the minimum thickness is determined by its strength, as well as its puncture resistance and tear resistance.

[0084] This disclosure also provides and includes a substantially oxygen-permeable membrane 113 prepared using blow molding and injection molding techniques. Suitable materials for preparing the internal collapsible blood container 102 using blow molding and injection molding include siloxane materials, such as Bluestar 4350 with a hardness of 50, Silbione-grade liquid siloxane rubber, and Shin-Etsu KEG-2000-40A / B liquid siloxane. Careful selection of siloxane hardness is taken into account for collapsibility and permeability, followed by well-controlled wall thickness. Thinner materials will have higher permeability. Methods for preparing the blow-molded and injection-molded collapsible blood container 102 are known in the art, for example, U.S. Patent 4,398,642 to Okudaira et al.; U.S. Patent 7,666,486 to Sato et al.; U.S. Patent 8,864,735 to Sano et al.; and U.S. Patent Application Publication No. 2012 / 0146266 to Oda et al. On one hand, LDPE, used for manufacturing collapsible water containers, can be used to prepare blow-molded collapsible blood containers 102. As provided below, suitable blow-molded or injection-molded collapsible blood containers 102 have an oxygen permeability of at least about 25 lbs.

[0085] According to one aspect of this disclosure, the collapsible blood container 102 can be manufactured from a microporous membrane 113 by various sealing methods, such as heat sealing, heat riveting, and adhesive bonding. According to one aspect of this disclosure, a pair of PVDF microporous membranes are bonded together around a periphery, wherein a portion of the PVC inlet fitting is secured in place at the joint using an adhesive (such as Loctite 4011) along with an adhesive primer (such as Loctite 770). According to another aspect of this disclosure, the collapsible blood container can be manufactured from a pair of microporous membranes by heat-sealing the four edges of the membrane pair together, wherein a portion of the multilayer fitting is sealed in the joint to provide fluid connectivity.

[0086] This disclosure provides and includes a collapsible blood container 102 made of more than one type of membrane 113. In one aspect, the collapsible blood container 102 includes a first membrane 113 and a second membrane 114 suitably bonded together to form the container. As used herein, membrane 114 generally refers to a membrane identical to membrane 113. That is, the collapsible blood container 102 is generally made of two connected membranes 113. This disclosure provides and includes a collapsible blood container 102 made of membranes 113 and 114 comprising different materials. Figure 1C As shown, the collapsible blood container 102 is illustrated as being made of membranes 113 and 114. Unless otherwise specified, it should be understood that membranes 113 and 114 are interchangeable. In another aspect, the collapsible blood container 102 includes a membrane 113 combined with a second membrane 114, the permeability of which is less than about 30% of the permeability of the first membrane 113. In some aspects, the second membrane 114 includes a relatively impermeable or insufficiently permeable membrane capable of providing sufficient deoxygenation on its own, but may be combined with a suitable membrane 113. In some aspects, the second membrane 114 is relatively impermeable. In another aspect, the second membrane 114 includes a molded membrane incorporated with ridges, baffles, or other structures to facilitate mixing. In one aspect, the second membrane 114 may include a rigid structure connected to the oxygen-permeable membrane 113. In aspects according to this disclosure, the second membrane 114 is heat-sealed to the membrane 113.

[0087] In some respects, the internal collapsible blood container 102 includes flow baffles located inside or outside the blood contact area, which provide an increase in turbulence within the collapsible blood container 102 when agitated. In one respect, the baffles are located between 1 and 2 inches apart and occupy 10% to 45% of the area of ​​the internal collapsible blood container 102.

[0088] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a microporous membrane made of polyvinylidene fluoride (PVDF). In some respects, the PVDF membrane is a substantially oxygen-permeable hydrophobic microporous membrane.

[0089] According to aspects of this disclosure, the microporous PVDF membrane includes pores ranging from 0.01 μm to 2.0 μm. In other aspects, the microporous PVDF membrane 113 includes pores ranging from 0.01 μm to 1.0 μm. In some aspects, the microporous PVDF membrane 113 has a pore size with a diameter between 0.03 μm and 1.0 μm. In other aspects, the microporous PVDF membrane 113 has a pore size with a diameter between 0.03 μm and 0.45 μm.

[0090] According to one aspect of this disclosure, the porosity of the PVDF membrane 113 used to prepare the collapsible blood container 102 is between 20% and 80%. In another aspect, the porosity of the PVDF membrane 113 used to prepare the collapsible blood container 102 is between 35% and 50%.

[0091] In some respects, the permeability of PVDF membranes with micropores larger than about 1.0 μm allows fluids to permeate through the membrane, thereby impairing fluid closure as well as oxygen and carbon dioxide permeability. To overcome this permeability at high pore sizes, so-called “superhydrophobic” membranes can be employed, where the contact angle is greater than 150°. As used herein and known in the art, the contact angle quantifies the wettability of a solid surface and is theoretically described by Young's equation. In some aspects of this disclosure, the use of non-hydrophobic PVDF materials is not recommended because the surface tension of such materials is low and allows fluids to leak through pores even within the aforementioned range.

[0092] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a PVDF permeable membrane 113 having a pore size with a diameter between 0.1 μm and 0.8 μm. In other aspects, the diameter of the micropores in the porous PVDF membrane can be from 0.22 μm to 0.8 μm. In one aspect, the micropores of the porous PVDF membrane are from 0.2 μm to 1.0 μm. In another aspect, the micropores of the porous PVDF membrane can be greater than 0.1 μm and less than 1.0 μm. In yet another aspect, the micropores of the porous PVDF membrane range from about 0.05 μm to about 1.0 μm. In some aspects, the micropores of the porous PVDF membrane can be greater than 0.3 μm or 0.4 μm. In other aspects, the micropores of the porous PVDF membrane can be greater than 0.5 μm or 0.6 μm.

[0093] According to one aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PVDF membrane 113 with a micropore size of less than 1.0 μm. According to another aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PVDF membrane 113 with a micropore size of less than 0.8 μm. According to certain aspects of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PVDF membrane 113 with a micropore size of less than 0.65 μm. According to another aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PVDF membrane 113 with a micropore size of less than 0.45 μm.

[0094] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.1 μm. In another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.22 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.20 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.45 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.65 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PVDF membrane 113 with a micropore size of 0.8 μm.

[0095] According to aspects of this disclosure, the PVDF membrane thickness may be less than 250 μm. In some aspects, the membrane thickness is greater than 10 μm. In some aspects, the PVDF membrane thickness may be between 10 μm and 250 μm. In other aspects, the PVDF membrane thickness may be between 10 μm and 125 μm or between 25 μm and 150 μm. In one aspect, the PVDF membrane thickness may be between 50 μm and 125 μm, between 75 μm and 125 μm, between 50 μm and 150 μm, between 75 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm. In one aspect, the membrane 113 of the internally foldable blood container 102 has a thickness of approximately 20 μm. In another aspect, the membrane 113 of the internally foldable blood container 102 has a thickness of approximately 30 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 50 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 76 μm. On yet another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 120 μm.

[0096] According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PVDF permeable membrane 113 with a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PVDF permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PVDF permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 50 μm and 150 μm.

[0097] Examples of suitable PVDF membranes for preparing oxygen-permeable internal collapsible blood containers according to this disclosure include VVSP with a thickness of 115 μm and pore size of 0.1 μm; GVSP with a thickness of 115 μm and pore size of 0.22 μm; HVSP with a thickness of 115 μm and pore size of 0.45 μm; DVSP with a thickness of 115 μm and pore size of 0.65 μm; BVSP with a thickness of 115 μm and pore size of 1.0 μm; VVHP with a thickness of 107 μm and pore size of 0.1 μm; GVHP with a thickness of 125 μm and pore size of 0.22 μm; HVHP with a thickness of 115 μm and pore size of 0.45 μm; or DVHP with a thickness of 115 μm and pore size of 0.65 μm.

[0098] Suitable PVDF membranes include commercially available membranes. Non-limiting examples of PVDF membranes are available from Millipore Corporation, Bedford, MA. In one aspect, PVDF membranes are available from Millipore Corporation, Bedford, MA. Examples of such PVDF membranes are VVSP, GVSP, HVSP, DVSP, BVSP, VVHP, GVHP, HVHP, or DVHP.

[0099] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a microporous membrane made of polysulfone. In some respects, the polysulfone membrane is a substantially oxygen-permeable hydrophobic microporous membrane.

[0100] According to aspects of this disclosure, the microporous polysulfone membrane includes pores ranging from 0.01 μm to 2.0 μm. In other aspects, the microporous polysulfone membrane 113 includes pores ranging from 0.01 μm to 1.0 μm. In some aspects, the microporous polysulfone membrane 113 has a pore size with a diameter between 0.03 μm and 1.0 μm. In other aspects, the microporous polysulfone membrane 113 has a pore size with a diameter between 0.03 μm and 0.45 μm.

[0101] According to one aspect of this disclosure, the porosity of the polysulfone membrane 113 used to prepare the foldable blood container 102 is between 20% and 80%. In another aspect, the porosity of the polysulfone membrane 113 used to prepare the foldable blood container 102 is between 35% and 50%.

[0102] In some respects, permeable polysulfone membranes with micropores larger than about 0.2 μm can allow fluids to permeate through the membrane, thereby compromising fluid closure as well as oxygen and carbon dioxide permeability. To overcome this permeability at high pore sizes, so-called “superhydrophobic” membranes can be employed, where the contact angle is greater than 150°. As used herein and known in the art, the contact angle quantifies the wettability of a solid surface and is theoretically described by Young’s equation. In some aspects of this disclosure, the use of non-hydrophobic polysulfone materials is not recommended because these materials have low surface tension and allow fluids to leak through pores even in the aforementioned range.

[0103] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a polysulfone permeable membrane 113 having a pore size with a diameter between 0.3 μm and 0.8 μm. In other aspects, the diameter of the micropores in the porous polysulfone membrane can be from 0.22 μm to 0.8 μm. In one aspect, the micropores in the porous polysulfone membrane are from 0.2 μm to 1.0 μm. In another aspect, the micropores in the porous polysulfone membrane can be greater than 0.1 μm and less than 1.0 μm. In yet another aspect, the micropores in the porous polysulfone membrane range from about 0.05 μm to about 1.0 μm. In some aspects, the micropores in the porous polysulfone membrane can be greater than 0.3 μm or 0.4 μm. In other aspects, the micropores in the porous polysulfone membrane can be greater than 0.5 μm or 0.6 μm.

[0104] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polysulfone membrane 113 with a micropore size of less than 1.0 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polysulfone membrane 113 with a micropore size of less than 0.8 μm. According to certain aspects of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polysulfone membrane 113 with a micropore size of less than 0.65 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polysulfone membrane 113 with a micropore size of less than 0.45 μm.

[0105] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.1 μm. In another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.22 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.20 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.45 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.65 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.8 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.03 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 0.05 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a polysulfone membrane 113 with a micropore size of 1.2 μm.

[0106] According to aspects of this disclosure, the polysulfone film thickness may be less than 250 μm. In some aspects, the film thickness is greater than 10 μm. In some aspects, the polysulfone film thickness may be between 10 μm and 250 μm. In other aspects, the polysulfone film thickness may be between 10 μm and 125 μm or between 25 μm and 150 μm. In one aspect, the polysulfone film thickness may be between 50 μm and 125 μm, between 75 μm and 125 μm, between 50 μm and 150 μm, between 75 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm. In one aspect, the membrane 113 of the internally foldable blood container 102 has a thickness of about 20 μm. In another aspect, the membrane 113 of the internally foldable blood container 102 has a thickness of about 30 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 50 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 76 μm. On yet another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 120 μm.

[0107] According to certain aspects of this disclosure, the foldable blood container 102 is prepared from a polysulfone permeable membrane 113 with a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the foldable blood container 102 is prepared from a polysulfone permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the foldable blood container 102 is prepared from a polysulfone permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 50 μm and 150 μm.

[0108] Examples of suitable polysulfone membranes for preparing oxygen-permeable internal foldable blood containers according to this disclosure include SS003AH with a thickness of 10-250 μm and pore size of 0.03 μm; SS005AH with a thickness of 10-250 μm and pore size of 0.05 μm; SS010AH with a thickness of 10-250 μm and pore size of 0.1 μm; SS020AH with a thickness of 10-250 μm and pore size of 0.2 μm; SS045AH with a thickness of 10-250 μm and pore size of 0.45 μm; SS065AH with a thickness of 10-250 μm and pore size of 0.65 μm; SS080AH with a thickness of 10-250 μm and pore size of 0.8 μm; or SS120AH with a thickness of 10-250 μm and pore size of 1.2 μm.

[0109] Suitable polysulfone membranes include commercially available membranes. Non-limiting examples of polysulfone membranes are available from PacificMembranes. In one aspect, the polysulfone membrane may be SS120AH, SS080AH, SS065AH, SS045AH, SS020AH, SS010AH, SS005AH, or SS003AH.

[0110] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a microporous membrane made of polyolefin. In some respects, the polyolefin membrane is a substantially oxygen-permeable hydrophobic microporous membrane.

[0111] According to aspects of this disclosure, the microporous polyolefin membrane includes pores ranging from 0.01 μm to 2.0 μm. In other aspects, the microporous polyolefin membrane 113 includes pores ranging from 0.01 μm to 1.0 μm. In some aspects, the microporous polyolefin membrane 113 has a pore size with a diameter between 0.03 μm and 1.0 μm. In other aspects, the microporous polyolefin membrane 113 has a pore size with a diameter between 0.03 μm and 0.45 μm.

[0112] According to one aspect of this disclosure, the porosity of the polyolefin membrane 113 used to prepare the collapsible blood container 102 is between 20% and 80%. In another aspect, the porosity of the polyolefin membrane 113 used to prepare the collapsible blood container 102 is between 35% and 50%.

[0113] In some respects, permeable polyolefin membranes with micropores larger than about 1.0 μm can allow fluids to permeate through the membrane, thereby compromising fluid closure and oxygen and carbon dioxide permeability. To overcome this permeability at high pore sizes, so-called “superhydrophobic” membranes can be employed, wherein the contact angle is greater than 150°. As used herein and known in the art, the contact angle quantifies the wettability of a solid surface and is theoretically described by Young's equation. In some aspects of this disclosure, the use of non-hydrophobic polyolefin materials is not recommended because these materials have low surface tension and allow fluids to leak through pores even within the aforementioned range.

[0114] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a polyolefin permeable membrane 113 having a pore size with a diameter between 0.1 μm and 0.8 μm. In other aspects, the diameter of the micropores in the porous polyolefin membrane can be from 0.22 μm to 0.8 μm. In one aspect, the micropores of the porous polyolefin membrane are from 0.2 μm to 1.0 μm. In another aspect, the micropores of the porous polyolefin membrane can be greater than 0.1 μm and less than 1.0 μm. In yet another aspect, the micropores of the porous polyolefin membrane range from about 0.05 μm to about 1.0 μm. In some aspects, the micropores of the porous polyolefin membrane can be greater than 0.3 μm or 0.4 μm. In other aspects, the micropores of the porous polyolefin membrane can be greater than 0.5 μm or 0.6 μm.

[0115] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of less than 1.0 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of less than 0.8 μm. According to certain aspects of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of less than 0.65 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of less than 0.45 μm.

[0116] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.1 μm. In another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.22 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.20 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.45 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.65 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a polyolefin membrane 113 with a micropore size of 0.8 μm.

[0117] According to aspects of this disclosure, the polyolefin membrane thickness may be less than 250 μm. In some aspects, the membrane thickness is greater than 10 μm. In some aspects, the polyolefin membrane thickness may be between 10 μm and 250 μm. In other aspects, the polyolefin membrane thickness may be between 10 μm and 125 μm or between 25 μm and 150 μm. In one aspect, the polyolefin membrane thickness may be between 50 μm and 125 μm, between 75 μm and 125 μm, between 50 μm and 150 μm, between 75 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm. In one aspect, the membrane 113 of the internally collapsible blood container 102 has a thickness of about 20 μm. In another aspect, the membrane 113 of the internally collapsible blood container 102 has a thickness of about 30 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 50 μm. On another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 76 μm. On yet another front, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 120 μm.

[0118] According to certain aspects of this disclosure, the collapsible blood container 102 is made of a polyolefin permeable membrane 113 with a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a polyolefin permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a polyolefin permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 50 μm and 150 μm.

[0119] Examples of suitable polyolefin membranes for preparing oxygen-permeable internal collapsible blood containers according to this disclosure include the polyolefin membranes described in U.S. Patent 4,440,815 to Zomorodi et al.

[0120] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a microporous membrane made of polytetrafluoroethylene (PTFE). In some respects, the PTFE membrane is a substantially oxygen-permeable hydrophobic microporous membrane.

[0121] According to aspects of this disclosure, the microporous PTFE membrane includes pores ranging from 0.01 μm to 2.0 μm. In other aspects, the microporous PTFE membrane 113 includes pores ranging from 0.01 μm to 1.0 μm. In some aspects, the microporous PTFE membrane 113 has a pore size with a diameter between 0.03 μm and 1.0 μm. In other aspects, the microporous PTFE membrane 113 has a pore size with a diameter between 0.03 μm and 0.45 μm.

[0122] According to one aspect of this disclosure, the porosity of the PTFE membrane 113 used to prepare the collapsible blood container 102 is between 20% and 80%. In another aspect, the porosity of the PTFE membrane 113 used to prepare the collapsible blood container 102 is between 35% and 50%.

[0123] In some respects, the permeability of PTFE membranes with micropores larger than about 1.0 μm allows fluids to permeate through the membrane, thereby impairing fluid closure as well as oxygen and carbon dioxide permeability. To overcome this permeability at high pore sizes, so-called “superhydrophobic” membranes can be employed, where the contact angle is greater than 150°. As used herein and known in the art, the contact angle quantifies the wettability of a solid surface and is theoretically described by Young's equation. In some aspects of this disclosure, the use of non-hydrophobic PTFE materials is not recommended because these materials have low surface tension and allow fluids to leak through pores even within the aforementioned range.

[0124] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a PTFE permeable membrane 113 having a pore size with a diameter between 0.1 μm and 0.8 μm. In other aspects, the diameter of the micropores in the porous PTFE membrane can be from 0.22 μm to 0.8 μm. In one aspect, the micropores of the porous PTFE membrane are from 0.2 μm to 1.0 μm. In another aspect, the micropores of the porous PTFE membrane can be greater than 0.1 μm and less than 1.0 μm. In yet another aspect, the micropores of the porous PTFE membrane range from about 0.05 μm to about 1.0 μm. In some aspects, the micropores of the porous PTFE membrane can be greater than 0.3 μm or 0.4 μm. In other aspects, the micropores of the porous PTFE membrane can be greater than 0.5 μm or 0.6 μm.

[0125] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PTFE membrane 113 with a micropore size of less than 1.0 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PTFE membrane 113 with a micropore size of less than 0.8 μm. According to certain aspects of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PTFE membrane 1113 with a micropore size of less than 0.65 μm. According to another aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a PTFE membrane 113 with a micropore size of less than 0.45 μm.

[0126] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.1 μm. In another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.22 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.20 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.45 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.65 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102, which includes a PTFE membrane 113 with a micropore size of 0.8 μm.

[0127] According to aspects of this disclosure, the thickness of the PTFE membrane 113 may be less than 250 μm. In some aspects, the membrane thickness is greater than 10 μm. In some aspects, the thickness of the PTFE membrane 113 may be between 10 μm and 250 μm. In other aspects, the thickness of the PTFE membrane 113 may be between 10 μm and 125 μm or between 25 μm and 150 μm. In one aspect, the thickness of the PTFE membrane 113 may be between 50 μm and 125 μm, between 75 μm and 125 μm, between 50 μm and 150 μm, between 75 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm. In another aspect, the membrane 113 of the internally foldable blood container 102 is about 30 μm. In yet another aspect, the membrane 113 of the internally foldable blood container 102 is about 50 μm. On the other hand, the membrane 113 of the internal collapsible blood container 102 is about 76 μm. On the other hand, the thickness of the membrane 113 of the internal collapsible blood container 102 is about 120 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm.

[0128] According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PTFE permeable membrane 113 with a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PTFE permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is made of a PTFE permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 50 μm and 150 μm.

[0129] Examples of suitable PTFE membranes for preparing oxygen-permeable internally collapsible blood containers according to this disclosure include those from Sumitomo Electric Interconnect Products, San Marcos, CA. FP, WP, and HP series PTFE membranes, as well as those from Donaldson Membranes, Ivyland, and PA. 2.

[0130] Suitable PTFE membranes include those that are commercially available. Non-limiting examples of PTFE membranes are available from Sumitomo Electric Interconnect Products, San Marcos, CA, and Donaldson Membranes, Ivyland, PA. In one aspect, the PTFE membrane may be FP-010 from Sumitomo Electric Interconnect Products, San Marcos, CA.

[0131] In some respects, a suitable membrane that is substantially permeable to oxygen can be a multilayer membrane. In some respects, a multilayer membrane is a hydrophobic microporous membrane that is substantially permeable to oxygen. Suitable multilayer membranes include those consisting of two or more materials selected from the group consisting of: hydrophobic PVDF, nylon, cellulose ester, polysulfone, polyethersulfone, hydrophobic polypropylene, and polyacrylonitrile.

[0132] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a microporous membrane prepared from an extruded, woven, or non-woven single-layer or multi-layer membrane. In some respects, the multilayer membrane is a substantially oxygen-permeable hydrophobic microporous membrane.

[0133] According to aspects of this disclosure, the microporous multilayer membrane includes pores ranging from 0.01 micrometers (μm) to 2.0 μm. In other aspects, the microporous multilayer membrane 113 includes pores ranging from 0.01 μm to 1.0 μm. In some aspects, the microporous multilayer membrane 113 has a pore diameter between 0.03 μm and 1.0 μm. In other aspects, the microporous multilayer membrane 113 has a pore diameter between 0.03 μm and 0.45 μm.

[0134] According to one aspect of this disclosure, the porosity of the multilayer membrane 113 used to prepare the collapsible blood container 102 is between 20% and 80%. In another aspect, the porosity of the multilayer membrane 113 used to prepare the collapsible blood container 102 is between 35% and 50%.

[0135] In some respects, the permeability of multilayer membranes with micropores larger than about 1.0 μm allows fluids to permeate through the membrane, thereby impairing fluid closure as well as oxygen and carbon dioxide permeability. To overcome this permeability at high pore sizes, so-called “superhydrophobic” membranes can be employed, where the contact angle is greater than 150°. As used herein and known in the art, the contact angle quantifies the wettability of a solid surface and is theoretically described by Young's equation. In some aspects of this disclosure, the use of non-hydrophobic multilayer materials is not recommended because these materials have low surface tension and allow fluids to leak through pores even within the aforementioned range.

[0136] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a multilayer permeable membrane 113 having a pore size with a diameter between 0.1 μm and 0.8 μm. In other aspects, the diameter of the micropores in the porous multilayer membrane can be from 0.22 μm to 0.8 μm. In one aspect, the micropores of the porous multilayer membrane are from 0.2 μm to 1.0 μm. In another aspect, the micropores of the porous multilayer membrane can be greater than 0.1 μm and less than 1.0 μm. In yet another aspect, the micropores of the porous multilayer membrane range from about 0.05 μm to about 1.0 μm. In some aspects, the micropores of the porous multilayer membrane can be greater than 0.3 μm or 0.4 μm. In other aspects, the micropores of the porous multilayer membrane can be greater than 0.5 μm or 0.6 μm.

[0137] According to one aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of less than 1.0 μm. According to another aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of less than 0.8 μm. According to certain aspects of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of less than 0.65 μm. According to another aspect of the present disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of less than 0.45 μm.

[0138] According to one aspect of this disclosure, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.1 μm. In another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.22 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.20 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.45 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.65 μm. In yet another aspect, the oxygen consumption device 10 includes an internal collapsible blood container 102 comprising a multilayer membrane 113 with a micropore size of 0.8 μm.

[0139] According to aspects of this disclosure, the thickness of the multilayer film 113 may be less than 250 μm. In some aspects, the film thickness is greater than 10 μm. In some aspects, the thickness of the multilayer film 113 may be between 10 μm and 250 μm. In other aspects, the thickness of the multilayer film may be between 10 μm and 125 μm or between 25 μm and 150 μm. In one aspect, the thickness of the multilayer film 113 may be between 50 μm and 125 μm, between 75 μm and 125 μm, between 50 μm and 150 μm, between 75 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm, between 100 μm and 125 μm, between 150 μm and 250 μm, or between 25 μm and 150 μm. On the other hand, the membrane 113 of the internal collapsible blood container 102 is approximately 30 μm. On yet another side, the membrane 113 of the internal collapsible blood container 102 is approximately 50 μm. On yet another side, the membrane 113 of the internal collapsible blood container 102 is approximately 76 μm. On yet another side, the membrane 113 of the internal collapsible blood container 102 has a thickness of approximately 120 μm.

[0140] According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a multilayer permeable membrane 113 with a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a multilayer permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 100 μm and 125 μm. According to certain aspects of this disclosure, the collapsible blood container 102 is prepared from a multilayer permeable membrane 113 having a pore size between 0.1 μm and 0.8 μm and a thickness between 50 μm and 150 μm.

[0141] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a membrane made of polyvinyl chloride (PVC). According to aspects of this disclosure, the collapsible blood container 102 may be made of a PVC membrane with a thickness between 5 μm and 250 μm, and more preferably between about 10 μm and about 100 μm.

[0142] The use of PVC in the manufacture of collapsible blood containers is well known in the art. The use of various plasticizers in various PVC formulations is also well known in the art, including the use of diethylhexyl phthalate (DEHP) for long-term storage of red blood cells. Typical collapsible blood containers made of PVC-DEHP utilize radio frequency (RF) welding of a pair of membranes to facilitate the fabrication of the bag structure, wherein such individual membranes have a thickness of approximately 350 μm to approximately 400 μm. An exemplary PVC-DEHP membrane is the Renolit ES-3000 membrane (American Renolit Corp., City of Commerce, CA).

[0143] Because such membranes have relatively low oxygen permeability and higher oxygen permeability is required for platelet storage, other plasticizers for PVC have been found to be useful in the manufacture of collapsible blood containers, including the use of citrates (see, for example, Colin R. Blass, “The Role of Poly(Vinyl Chloride) in Healthcare,” copyright 2001 Rapra Technology, Ltd., ISBN: 1-85957-258-8). A suitable example of a PVC-citrate membrane is the Renolit ES-4000 membrane (American Renolit Corp., City of Commerce, CA).

[0144] This disclosure provides suitable PVC materials for use in a substantially oxygen-permeable collapsible blood container 102. The use of PVC-citrate membranes (such as Renolit ES-4000) with a thickness of about 5 μm to about 250 μm, and more preferably about 10 μm to about 100 μm, is suitable for providing collapsible blood containers with the desired characteristics of high oxygen permeability, RF welding and bonding, and high tensile strength.

[0145] This disclosure provides and includes a collapsible blood container 102, which is substantially oxygen-permeable and is a membrane made of siloxane. According to one aspect of this disclosure, the collapsible blood container 102 can be made of a siloxane membrane with a thickness between 15 μm and 100 μm. According to another aspect of this disclosure, the collapsible blood container 102 can be made of a siloxane membrane with a thickness between 5 μm and 500 μm. In other aspects, the thickness of the collapsible blood container 102 can be between 5 μm and 200 μm. In other aspects, the thickness of the collapsible blood container 102 can be between 20 μm and 120 μm. In another aspect, the thickness of the collapsible blood container 102 is between 30 μm and 120 μm. In yet another aspect, the thickness of the collapsible blood container 102 is between 50 μm and 120 μm. In another aspect, the thickness of the collapsible blood container 102 can be between 76 μm and 120 μm. In another aspect, the thickness of the collapsible blood container 102 is between 20 μm and 50 μm. This disclosure provides and includes a collapsible blood container 102 with a thickness of 20 μm. In another aspect, the collapsible blood container 102 has a thickness of 15 μm. In yet another aspect, the collapsible blood container 102 has a thickness of 30 μm. In yet another aspect, the collapsible blood container 102 has a thickness of 50 μm. In yet another aspect, the collapsible blood container 102 has a thickness of 120 μm.

[0146] According to one aspect of this disclosure, the foldable blood container 102 can be fabricated from a siloxane film with a thickness between 20 μm and 400 μm. In other aspects, the thickness of the foldable blood container 102 can be between 20 μm and 200 μm. In other aspects, the thickness of the foldable blood container 102 can be between 40 μm and 300 μm. In another aspect, the thickness of the foldable blood container 102 is between 40 μm and 400 μm. In yet another aspect, the thickness of the foldable blood container 102 is between 300 μm and 450 μm. In yet another aspect, the thickness of the foldable blood container 102 can be between 350 μm and 450 μm. This disclosure provides and includes a foldable blood container 102 with a thickness of about 450 μm. In another aspect, the thickness of the foldable blood container 102 is 425 μm. In yet another aspect, the thickness of the foldable blood container 102 is 400 μm. In yet another aspect, the thickness of the foldable blood container 102 is 350 μm.

[0147] Suitable siloxane membranes include commercially available membranes. Non-limiting examples of siloxane membranes are available from WackerSilicones, such as... The brand's medical-grade silicone sheet film (Wacker Silicones, Adrian, MI) and Polymer Sciences PS-1033 Siloxane elastomer membrane (Polymer Sciences, Inc., Monticello, IN). On one hand, the siloxane membrane can be Polymer Sciences PS-1033 or Wacker. 6000 siloxane. Siloxane films can be prepared from various liquid siloxane rubber (LSR) materials, which are available from many siloxane suppliers, such as Wacker Silicones (Adrian, MI), Shin-EtsuSilicones (Akron, OH), NuSil Technology (Carpenteria, CA), and Blue Star Silicones (East Brunswick, NJ).

[0148] According to one aspect of this disclosure, the collapsible blood container 102 can be manufactured from siloxane by various molding methods (such as compression molding, injection molding, and insert molding), and can also be manufactured by bonding siloxane sheets using a siloxane adhesive. According to one aspect of this disclosure, a pair of siloxane sheets are bonded together around a perimeter, wherein a portion of the siloxane inlet tube is secured in place at the joint using a siloxane adhesive. According to another aspect of this disclosure, siloxane liquid rubber is injection molded onto a template to form a three-sided shape, and then the three-sided shape is further bonded using a siloxane adhesive to close the remaining fourth facet surrounding the siloxane inlet tube. According to another aspect of this disclosure, siloxane liquid rubber is injection molded onto a template to form a three-sided shape, and then the three-sided shape is inserted into a closed shape molded onto the remaining fourth facet, which incorporates the inlet tube into the closed shape.

[0149] This disclosure provides and includes a collapsible blood container 102 with tear resistance. As used herein, “tear resistance” or “tear strength” is measured in kN / m. In aspects according to this disclosure, the collapsible blood container 102 should be made of an oxygen-permeable material that also resists tearing. Measurements of tear resistance are known in the art, for example, ASTM D-412, and can also be used to measure tensile strength, modulus, and elongation. In some aspects, the collapsible blood container 102 should be made of an oxygen-permeable material that resists tear formation (e.g., tear initiation). Methods for measuring tear initiation and tear propagation are known in the art, for example, ASTM D-624. Other methods include measuring tensile strength and elongation at break according to DIN 53504-S1.

[0150] According to one aspect of this disclosure, the collapsible blood container 102 shall be made of material with a tensile strength of at least 2.4 N / mm². 2 Preparation of oxygen-permeable materials.

[0151] This disclosure provides and includes adsorbents capable of binding to and removing oxygen from the environment. Unless otherwise provided, the term "adsorbent" refers to both oxygen adsorbents and oxygen scavengers. As used herein, "oxygen scavenger" or "oxygen adsorbent" is a material that irreversibly binds to or combines with O2 under conditions of use. The term "oxygen adsorbent" may be used interchangeably with "oxygen scavenger" herein. In some aspects according to this disclosure, the material may irreversibly bind to or combine with oxygen. In other aspects, oxygen may bind to the adsorbent material and have a very slow release rate k. off On the one hand, oxygen can react chemically with some components of a material and transform into another compound. Any material in which the dissociation rate of bound oxygen is much lower than the blood residence time can be used as an oxygen scavenger.

[0152] As used herein, the amount of adsorbent is provided to have the following properties as described above: [The text abruptly ends here, so the translation stops as well.] 5 The oxygen-binding capacity is a measure of the volume (e.g., cubic centimeters (cc) or milliliters (ml)) under a pressure of 100 kPa (1 bar, 0.986 atm, 760 mmHg). In other respects, oxygen adsorbents and oxygen scavengers are also capable of binding with and removing carbon dioxide from the environment. In some respects, adsorbent 103 may be a mixture of non-toxic inorganic salts and / or organic salts with ferrous iron or other materials highly reactive to oxygen, carbon dioxide, or both. In some respects, oxygen adsorbents or oxygen scavengers are combined with carbon dioxide adsorbents. In other respects, the presence or absence of the carbon dioxide-binding capacity of the oxygen adsorbent is not essential.

[0153] Suitable oxygen adsorbents or oxygen scavengers are known in the art. The minimum oxygen adsorbent rate according to this disclosure is 0.44 ml / min. Adsorbents with suitable adsorption profiles bind at least 45 ml of O2 within 60 minutes, 70 ml of O2 within 120 minutes, and 80 ml of O2 within 180 minutes. Suitable adsorbents may have high capacity and binding rate.

[0154] Non-limiting examples of oxygen scavengers or oxygen adsorbents include iron powder and organic compounds. Examples of O2 adsorbents include chelates of cobalt, iron, and Schiff bases. Further non-limiting examples of O2 adsorbents can be found in U.S. Patent 7,347,887 to Bulow et al., U.S. Patent 5,208,335 to Ramprasad et al., and U.S. Patent 4,654,053 to Sievers et al., each of which is incorporated herein by reference in its entirety. Oxygen adsorbent materials can be formed as or incorporated into fibers, microfibers, microspheres, microparticles, and foams.

[0155] In some respects, suitable adsorbents include those available from Multisorb Technologies (Buffalo, NY), Sorbent Systems / Impak Corporation (Los Angeles, CA), or Mitsubishi Gas Chemical America (MGC) (New York, NY). Exemplary oxygen adsorbents include those from Multisorb Technologies. Package, adsorbent system P / N SF100PK100 100cc oxygen absorbent and Mitsubishi Gas Chemical America SS-200 oxygen absorbent. MGC also provides adsorbents suitable for the methods and apparatus of this disclosure. Such suitable oxygen adsorbents include MGC. And SS-200 oxygen absorbent.

[0156] According to aspects of this disclosure, the adsorbent can be an oxidizable organic polymer having a polymer backbone and multiple side groups. Examples of adsorbents having a polymer backbone include saturated hydrocarbons (<0.01% carbon-carbon double bonds). In some aspects, the backbone can contain monomers of ethylene or styrene. In one aspect, the polymer backbone can be ethylene. In another aspect, the oxidizable organic compound can be an ethylene / vinylcyclohexene copolymer (EVCH). Further examples of substituted moieties and catalysts are provided in U.S. Patent Publication No. 2003 / 0183801 by Yang et al., which is incorporated herein by reference in its entirety. In another aspect, the oxidizable organic polymer may also contain substituted hydrocarbon moieties. Examples of oxygen-scavenging polymers include those described in International Patent Publication WO99 / 48963 by Ching et al., which is incorporated herein by reference in its entirety. Oxygen scavenging materials may include those provided in U.S. Patent 7,754,798, U.S. Patent 7,452,601, or U.S. Patent 6,387,461 to Ebner et al., each of which is incorporated herein by reference in its entirety.

[0157] As used herein, the adsorbent of this disclosure may be free or contained in a permeable shell, container, tube, etc. In some aspects, the adsorbent is provided in one or more pouches made of a material having high porosity and being substantially resistant to gas transport. Examples of such materials include spun polyester films, perforated metal foils, and combinations thereof.

[0158] This disclosure also includes and provides an adsorbent incorporated into one or more laminated layers of a substantially oxygen-impermeable external article. Polymer adsorbents (such as those described above) can be laminated onto sheets used to prepare external receivers using methods known in the art, including soft-contact lamination, thermal lamination, or solvent lamination.

[0159] This disclosure also includes and provides adsorbents formed within the pores of porous microglass fibers or encapsulated in other inert materials. Encapsulation of transition metal complexes within the pores of porous materials can be achieved using ship-in-a-bottle synthesis, where the final molecule is prepared within the pores by reacting a small precursor. Examples of such encapsulated adsorbents are known in the art, for example, as described in Kuraoka et al., “Ship-in-a-bottle synthesis of a cobalt phthalocyanine / porous glass composite membrane for oxygen separation,” Journal of Membrane Science, 286(1-2): 12-14 (2006), which is incorporated herein by reference in its entirety. In some aspects, porous glass fibers can be manufactured as provided in U.S. Patent 4,748,121 to Beaver et al., which is incorporated herein by reference in its entirety. On the other hand, adsorbents can be formed into porous sheet products using paper / nonwoven wet web forming equipment. Sheets having an O2 scavenging agent can be formed and then encapsulated with a siloxane film, as described in U.S. Patent 4,769,175 to Inoue (which is incorporated herein by reference in its entirety).

[0160] As used herein, a “carbon dioxide scavenger” is a material that binds to or combines with carbon dioxide under conditions of use. The term “carbon dioxide adsorbent” may be used interchangeably with “carbon dioxide scavenger”. In some aspects, a carbon dioxide adsorbent may be non-reactive or minimally reactive with oxygen. In other embodiments, an oxygen adsorbent may exhibit a secondary function of carbon dioxide scavenging. Carbon dioxide scavengers include metal oxides and metal hydroxides. Metal oxides react with water to produce metal hydroxides. Metal hydroxides react with carbon dioxide to form water and metal carbonates. In some aspects according to this disclosure, the material may irreversibly bind to or combine with CO2. In aspects according to this disclosure, the material may bind CO2 with a higher affinity than hemoglobin. In other aspects, the adsorbent material may bind CO2 with a high affinity, causing carbonic acid present in the blood or RBC cytoplasm to be released and absorbed by the adsorbent. In other aspects, CO2 binds to the adsorbent material and has a very slow release rate k.off On the one hand, carbon dioxide can react chemically with some components of the material and be transformed into another compound.

[0161] Carbon dioxide scavengers are known in the art. According to certain aspects of this disclosure, the carbon dioxide scavenger may be calcium oxide. Calcium oxide reacts with water to produce calcium hydroxide, which can react with carbon dioxide to form calcium carbonate and water. According to certain aspects of this disclosure, the water used to produce calcium hydroxide is obtained by diffusion of blood-derived water vapor through an internal oxygen-permeable container. In another aspect, water may be supplied from the environment through a substantially oxygen-impermeable external receiver. In yet another aspect, water may be included in an external receiver of the oxygen-consuming device.

[0162] Non-limiting examples of CO2 scavengers include oxygen scavengers and carbon dioxide scavengers supplied by Multisorb Technologies (Buffalo, NY). Oxygen scavengers may exhibit secondary functionality in carbon dioxide removal.

[0163] According to aspects of this disclosure, the O2 consuming medium and the CO2 consuming medium can be blended to a desired ratio to achieve the desired result.

[0164] This disclosure also includes and provides an adsorbent contained in a pouch. As used herein, a "pouch" is any enclosed shell containing an oxygen adsorbent, a carbon dioxide adsorbent, or a combination of both. Pouches according to this disclosure are contained within an oxygen and carbon dioxide permeable outer packaging material. In some embodiments, the outer packaging material may be a combination of two or more materials, at least one of which is oxygen and carbon dioxide permeable. Suitable outer packaging materials have known biocompatibility characteristics or conform to ISO 10993.

[0165] The pouches are sealed so that the adsorbent contents are completely contained within the outer packaging material, and the adsorbent is not allowed to leak or otherwise leave its outer packaging. The pouches can take any shape, although they are typically rectangular or square. In one aspect, the pouch is approximately 50 x 60 mm. In one aspect, each pouch of oxygen adsorbent 103 binds 30 cc of oxygen under STP. In one aspect, each pouch of oxygen adsorbent 103 binds 60 cc of oxygen under STP. In one aspect, each pouch of oxygen adsorbent 103 binds 120 cc of oxygen under STP. In one aspect, each pouch of oxygen adsorbent 103 binds from 30 cc to 120 cc of oxygen under STP. In one aspect, each pouch of oxygen adsorbent 103 binds from 30 cc to 120 cc of oxygen under STP. In one aspect, each pouch of oxygen adsorbent 103 binds from 50 cc to 200 cc of oxygen under STP. According to certain aspects of this disclosure, the pouch has a total oxygen adsorption capacity of 100 cc O2 under STP. In some other aspects of this disclosure, the pouch has a total oxygen absorption capacity of at least 200 cc O2 under STP.

[0166] According to one aspect of this disclosure, the oxygen adsorbent 103 may be provided in one or more pouches. In another aspect, the oxygen adsorbent 103 may be provided in a single, larger pouch. In yet another aspect, the oxygen adsorbent 103 may be provided in two pouches distributed within the top space between the inner collapsible container 102 and the outer receiver 101. In yet another aspect, the oxygen adsorbent 103 may be provided in four pouches distributed within the top space between the inner collapsible container 102 and the outer receiver 101. According to one aspect of this disclosure, the oxygen consumption device 10 may include 2 to 20 adsorbent packages.

[0167] According to one aspect of this disclosure, the oxygen consumption device 10 includes 1 to 50 grams of adsorbent 103 contained in one or more small bags. In one aspect, the oxygen consumption device 10 includes 1 to 100 grams of adsorbent 103 contained in one or more small bags. In another aspect, the oxygen consumption device 10 includes 25 to 75 grams of adsorbent 103 contained in one or more small bags. In yet another aspect, the oxygen consumption device 10 includes about 25 grams of adsorbent 103. In still another aspect, the oxygen consumption device 10 includes about 50 grams of adsorbent 103. In one aspect, the oxygen consumption device 10 includes about 35 or 45 grams of adsorbent 103 contained in one or more small bags. In yet another aspect, the oxygen consumption device 10 includes about 10 or 15 grams of adsorbent 103 contained in one or more small bags. The small bags may be square, rectangular, circular, or elliptical and have a perimeter of 40 to 150 mm.

[0168] The pouch according to this disclosure may also include a carbon dioxide adsorbent. In one aspect, an oxygen adsorbent 103 also provides carbon dioxide adsorption. In one aspect, the oxygen adsorbent 103 binds 30 cc of carbon dioxide under STP. In another aspect, the oxygen adsorbent 103 binds at least 170 cc of oxygen and at least 30 cc of carbon dioxide, wherein both gases are measured under STP.

[0169] This disclosure provides and includes an external receiver 101 that is substantially impermeable to oxygen. As stated above, the integrity of the oxygen barrier layer should be maintained when the external receiver 101 is joined, welded, folded, or otherwise assembled. Failure to assemble the external receiver 101 impairs the lifespan of the oxygen consumption device 10 or prevents it from performing its intended purpose of consuming oxygen from the blood. Importantly, blood that does not fully consume oxygen does not achieve the benefit of consumption during storage and may have significant negative consequences when transfused into a patient. In addition to meeting the requirements for blood collection and consumption, this is routine for the blood to be sampled through the standardized port 303 and for the various additives to be introduced into the collected blood. More specifically, almost all collected blood is provided with an anticoagulant at or during collection.

[0170] To address the need to introduce material into the collected blood and to transfer oxygen-depleted blood to a suitable anaerobic storage bag, the oxygen consumption device 10 may also include one or more inlets / outlets 30. As provided herein, particular attention is paid to the assembly of the external receivers 101 (and 201) to ensure that the inlets / outlets 30 do not become an undesirable source of oxygen ingress as the oxygen-impermeable external receivers 101 (and 201) move back and forth.

[0171] In aspects according to this disclosure, the external receiver 101 includes one or more inlets / outlets 30. In some aspects, the one or more inlets / outlets 30 also include a tip port 303.

[0172] It is worth noting that few materials offer complete impermeability, and even highly impermeable materials can be compromised when the external receiver 101 is joined, welded, folded, or otherwise assembled. As will be discussed below, the oxygen consumption device 10 may also incorporate optional pointed ports 303 and inlet / outlet 30, and must also be designed to accommodate volume changes in the internal collapsible blood container 102. Therefore, special attention must be paid to incorporating specific design elements and manufacturing methods to ensure the integrity of the impermeable barrier layer.

[0173] Tip ports 303 used in blood collection kits and systems are generally known in the art and include products such as Vitalmed #20391 (Vitalmed, Inc., Lakeville, MA) and Qosina 65842 (Qosina Corp., Edgewood, NY). These ports are typically molded from PVC and have a removable cap that provides a sterile barrier layer before use and also provides a degree of oxygen impermeability to the contents. In some aspects, tip ports 303 are covered by a sealed, fragile portion of an external receiver membrane, thereby providing a sterile barrier layer and also providing an additional degree of oxygen impermeability. Improved oxygen impermeability is needed because it increases the lifespan of kits and systems with oxygen-consuming devices 10.

[0174] As will be understood, conventional ports, inlets, and outlets are potential sources of unwanted oxygen ingress, which depends on the choice of materials and the method used to bond the ports, inlets, or outlets to the external receiver 101. Methods of bonding materials are well known in the art. As provided herein, the inlet / outlet 30 comprises a tube 301 connected to the external receiver 101 (or external receiver 201) using an adhesive 302 that creates an oxygen-impermeable seal against the external receiver 101 (or external receiver 201). In one aspect, the adhesive 302 is achieved by using a heat-sealing mold heated to and maintained at a constant temperature of approximately 210°F. In another aspect, a membrane is placed between the heated molds and clamped together to achieve a heat-welded joint. In some aspects, a heat seal is created within approximately 5 seconds. In some aspects, the sealing mold has a grooved cross-section machined therefrom to accommodate an intermediate assembly. In some aspects, the tube 301 includes an intermediate assembly, which may be a section of multi-layered tubing or a small piece of machined polymer or molding device, as discussed below. In some respects, the molding device is made of polyolefins (such as polyethylene). In aspects according to this disclosure, the size of the groove is set to be about 10% smaller than the feature of the component, thereby providing compression during sealing.

[0175] In some aspects, the oxygen-impermeable adhesive is formed by a portion of the multilayer tube in the heat-sealed joint to the outer receiver 101. In some aspects, the multilayer tube is formed by an outer polyethylene layer, an inner PVC (polyvinyl chloride) layer, and an intermediate EVA (ethylene-vinyl alcohol) layer (Pexco, Inc. Athol, MA). In some aspects, an additional portion of the PVC fitting is solvent-bonded to the multilayer tube using, for example, cyclohexanone.

[0176] In some aspects, the inlet / outlet 30 comprises a tube 301 made of polyethylene consisting of small diamond-shaped blocks with a central through-hole, such that the diamond blocks are heat-sealed into the seam of the outer receiver to provide an oxygen-impermeable adhesive 302, while the central through-hole provides fluid communication with the contents. In one aspect, a portion of the PVC fitting is bonded to the central hole of the diamond block using an oxygen-impermeable adhesive (such as Loctite 4310, Masterbond X17, or 3M Scothweld 4693) capable of bonding to polyethylene, thereby providing fluid communication through the oxygen-impermeable outer receiver to the contents therein. In other aspects, multi-layer fittings can be bonded to the central hole of the diamond block using methods known in the art. In still other aspects, multi-layer fittings can be used instead of standard PVC venous fittings to provide enhanced oxygen barrier properties.

[0177] Users of collapsible containers require convenient filling and emptying of contents, and according to the ISO 3826 standard for blood containers, the contents must be emptied within 2 minutes. An external receiver can reduce filling time by restraining the collapsible container and preventing it from expanding. Therefore, in some embodiments, the blood storage device also comprises an expansion feature to allow unrestricted filling of the collapsible container. In some embodiments, the expansion feature is formed by folding a gusset plate along one or more edges of the external receiver. Typically, a fold of about 1 / 4 inch is sufficient to provide expansion of the inner container, and the folded pleats are sealed in seams at the ends. In some embodiments, the expansion feature comprises a third panel of a barrier membrane sealed along the bottom of the external receiver, thereby providing a three-dimensional bag.

[0178] During the development of the oxygen consumption device 10, it was found that the size, shape, and number of chambers in the internal collapsible blood container 102 needed to be controlled to obtain suitable consumption kinetics. More specifically, even with highly permeable materials, the use of standard blood bag configurations has been found to be insufficient and have significantly slower reaction kinetics. Without being bound by theory, it is assumed that deoxygenation is a multi-step process involving the release of dissolved oxygen from hemoglobin, diffusion of dissolved oxygen within the cytoplasm of erythrocytes, and diffusion of dissolved oxygen across the erythrocyte cell membrane. Also without being bound by theory, it is assumed that high concentrations of hemoglobin with a very high affinity for oxygen significantly reduce the diffusion rate of dissolved oxygen within the cytoplasm. Similarly, once dissolved oxygen has crossed the plasma membrane into the plasma, its diffusion is also limited by absorption and binding with other erythrocytes. Again, without being bound by theory, it is assumed that an additional diffusion barrier layer for dissolved oxygen appears at the gas-permeable membrane, where dissolved oxygen not only needs to cross the membrane but also changes its state from dissolved to gaseous. Subsequent diffusion and adsorption by the adsorbent occur in the gaseous state and are maximized by incorporating and maintaining headspace within the external receiver 101. Therefore, it is believed that the diffusion of gaseous oxygen is maximized by maintaining a concentration gradient in the space from the surface of the internal collapsible blood container 102 to the top of the oxygen absorber 103. Furthermore, without being limited by theory, it is thought that by selecting an adsorbent with high absorption kinetics, high binding capacity, and a combination of both, a suitable diffusion gradient of gaseous oxygen can be maintained to drive the rapid kinetics of oxygen consumption in the oxygen consumption device 10.

[0179] This disclosure provides and includes an oxygen consumption device 10 for consuming oxygen from blood, comprising a surface-to-volume ratio of 4.75 cm² enclosed within an external receiver 101. 2 / ml (cm) 2 / ml) and 6.9cm 2 An internal collapsible blood container 102 with a volume ratio between [value] ml and [value]. In some aspects, the oxygen consumption device 10 for consuming oxygen from blood includes an internal collapsible blood container 102, which, when filled with blood for oxygen consumption, has a surface-to-volume ratio of 4.84 cm² within an external receiver 101. 2 / ml and 6.9cm 2 Between / ml. In some aspects, the oxygen consumption device 10 for consuming oxygen from blood includes an internal collapsible blood container 102, which, when filled with blood for oxygen consumption, has a surface-to-volume ratio of 5.0 cm² within an external receiver 101. 2 / ml and 6.9cm 2Between / ml. In some aspects, the oxygen consumption device 10 for consuming oxygen from blood includes an internal collapsible blood container 102, which, when filled with blood for oxygen consumption, has a surface-to-volume ratio of 5.0 cm² within an external receiver 101. 2 / ml and 6.5cm 2 Between / ml. In some aspects, the oxygen consumption device 10 for consuming oxygen from blood includes an internal collapsible blood container 102, which, when filled with blood for oxygen consumption, has a surface-to-volume ratio of 5.5 cm² within an external receiver 101. 2 / ml and 6.5cm 2 Between / ml.

[0180] As used herein, surface-to-volume and surface area-to-volume are used interchangeably throughout this disclosure. As used herein, the surface-to-volume ratio is defined relative to a standard unit of whole blood, approximately 1 pint or 450-500 ml. As will be apparent to those skilled in the art, collecting less than one unit of blood results in even higher surface-to-volume ratios, and the oxygen consumption device 10 is adapted to collect a portion of one unit of blood without modification. To collect more than one unit of blood, the dimensions of the collapsible blood container 102 need to be adjusted to provide the desired rapid kinetics of blood consumption. The type of modification necessary for collecting more than one unit of blood in the oxygen consumption device 10 is within the level of a person skilled in the art.

[0181] This disclosure also includes and provides an oxygen-consuming device 10 for collecting and consuming compressed red blood cells. A complete unit of compressed red blood cells in the additive solution contains approximately 280 ± 60 ml.

[0182] According to one aspect of this disclosure, when filled with blood for oxygen consumption, the surface-to-volume ratio of the collapsible blood container 102 is at least 4.84 cm. 2 / ml (cm) 2 / m1). Without being limited by theory, it is believed that by increasing the surface-to-volume ratio, the diffusion limitation imposed by the blood itself (especially red blood cells and hemoglobin) can be overcome by reducing the diffusion distance of dissolved oxygen within the internal collapsible blood container 102. In one aspect, when filled with blood for oxygen consumption, the surface-to-volume ratio of the blood container 102 is at least 5.0 cm². 2 / ml. On the other hand, when filled with blood for oxygen consumption, the surface-to-volume ratio of the collapsible blood container 102 is at least 5.5 cm². 2 / ml. On the other hand, when filled with blood for oxygen consumption, the surface-to-volume ratio of the collapsible blood container 102 is at least 6.0 cm². 2 / ml. In some respects, when filled with blood for oxygen consumption, the surface-to-volume ratio of the collapsible blood container 102 is at least 6.5 cm². 2 / ml.

[0183] This disclosure also includes and provides methods to increase the kinetics of blood deoxygenation by modifying the size of the internal collapsible blood container 102. Without being theoretically limited, the average diffusion distance of red blood cells in the blood is minimized with decreasing height, resulting in increased deoxygenation kinetics. According to some aspects of this disclosure, the collapsible blood container 102 has dimensions of 25.4 cm × 30.5 cm × 0.02 cm before being filled with blood, and a height of approximately 1.5 cm after being filled with blood. According to other aspects of this disclosure, the collapsible blood container 102 has dimensions of 17.5 cm × 28.0 cm (7 x 11 inches) × 0.04 cm before being filled with blood, and a height of approximately 2.0 cm after being filled with blood. According to other aspects of this disclosure, the collapsible blood container 102 has dimensions of 25.0 cm × 60.0 cm (10 x 23 inches) × 0.04 cm before being filled with blood, and a height of approximately 0.3 cm after being filled with blood.

[0184] In some aspects, the height of the collapsible blood container 102 when empty is no greater than 0.005 cm. In other aspects, the height of the collapsible blood container 102 is no greater than 0.1 cm. In some aspects, the height of the collapsible blood container 102 is between 0.002 cm and 0.1 cm. When filled with blood, the height of the collapsible blood container 102 is no greater than 0.3 cm. In other aspects, when filled with blood, the height of the collapsible blood container 102 is no greater than 1.5 cm. In some aspects, when filled with blood, the height of the collapsible blood container 102 is between 0.2 cm and 2.5 cm.

[0185] This disclosure also includes and provides an oxygen consumption device 10 having a size suitable for integration into existing blood collection schemes using existing equipment. Designing an oxygen consumption device 10 with prior art characteristics can reduce capital costs for centralized processing centers and also provide increased consistency and reliability. As used herein, the size of the oxygen consumption device 10 is primarily limited by the length and width of the external receiver 101, where the height of the bag is determined by the requirement that the collapsible blood container 102 contains approximately one pint or 450 ml to 500 ml of whole blood (which corresponds to one "unit of blood"). On the other hand, the collapsible blood container 102 is provided to contain 220 ml to 380 ml of compressed red blood cells, which corresponds to one unit of compressed red blood cells. The height of the oxygen consumption device 10 is also constrained by the presence of one or more included adsorbent packs and devices to maintain adequate headroom. In view of these considerations, it is apparent that the constraints on the size of the external receiver 101 of the oxygen consumption device 10 necessarily limit the size of the collapsible blood container 102. Therefore, the collapsible blood container 102 can be divided into one or more chambers in fluid communication with each other.

[0186] According to aspects of this disclosure, the oxygen consumption device 10 is designed to be integrated into existing blood agitation equipment. In some aspects, the size of the oxygen consumption device 10 is configured to efficiently utilize the space available in the agitator and mixing station. In another aspect, the size of the oxygen consumption device 10 is configured to maximize the use of the available area in a platelet agitator (e.g., the Helmer Labs Platelet Agitator PF96). Suitable sizes for the oxygen consumption device 10 include those that allow 1, 2, 4, 6, 8, 10, or more bags to be placed on a flat agitator or mixing surface.

[0187] The area of ​​the collapsible blood container 102 within the oxygen consumption device 10 has a depth of approximately 900 cm. 2 Up to 1800cm 2 The area between them. Therefore, the oxygen consumption device 10, which also includes spacer 110, effectively doubles the surface area available for gas exchange. In the absence of spacer 110, the exchange rate of the membrane 113 of the collapsible blood container 102 on the lower surface is significantly reduced, and the permeable membrane comes into contact with the impermeable membrane.

[0188] This disclosure provides and includes a collapsible blood container 102, which also includes a bonding layer 105, such as... Figure 1A , 1CAs shown in 6, 7, 9A, 9B, 10, and 11. As used herein, bonding layer 105 comprises an intermediate material that bonds (joins) membranes 113 (114) together. In some aspects, bonding layer 105 comprises a solid material having a defined shape. As discussed below, bonding layers having defined shapes provide the incorporation of geometric features 121 including rounded corners and other hybrid reinforcing shapes. In some aspects, bonding layer 105 comprises a liquid or gel that can be dried or cured to provide a bonding adhesion between membranes 113. Thus, a collapsible blood container 102 including a siloxane membrane 113 can be joined by a liquid siloxane bonding layer 105. In some aspects, siloxane bonding layer 116 may be a liquid siloxane rubber (LSR).

[0189] This disclosure provides and includes a collapsible blood container 102, which further includes a bonding layer 105 made of a solid material having a lower melting point than the membrane 113. By providing a bonding layer 105 with a lower melting temperature, the membrane 113 can be thermally bonded through the bonding layer 105 without compromising the structure of the microporous membrane, including melting and / or crystallization. In one aspect, the bonding layer 105 is selected to have a melting temperature at least 3°C ​​lower than the melting temperature of the microporous membrane 113. In other aspects, the bonding layer 105 has a melting temperature at least 10°C lower than the melting temperature of the microporous membrane 113. In still other aspects, a suitable bonding layer 105 is selected to maximize the temperature difference between the bonding layer and the microporous membrane 113 (114) to be bonded.

[0190] In one aspect of this disclosure, the bonding layer 105 is selected from LDPE, and the microporous membrane 113 is selected from the group consisting of polysulfone, hydrophobic polyvinylidene fluoride (PVDF), cellulose esters, mixed esters of cellulose (MCE), polyethersulfone (PES), hydrophobic polypropylene, and polyacrylonitrile. In one aspect, the bonding layer 105 is LDPE, and the microporous membrane 113 is polysulfone or hydrophobic polyvinylidene fluoride (PVDF). This disclosure provides and includes suitable microporous membrane selections as detailed in paragraphs

[0081] to

[00123] , and also includes multilayer membranes 113 as provided in paragraphs [001241] to [001331].

[0191] This disclosure provides and includes a construction of a collapsible blood container 102 having a bonding layer, wherein the bonding layer extends beyond the seal and is indicated as a gap 109, for example as... Figure 9B As shown.

[0192] This disclosure provides and includes a gap 109 in the space between the seal termination and the joint termination. In some aspects, the gap 109 is between 0.05 cm and 2.5 cm. In other aspects, the gap 109 has a width of at least 0.1 cm. In other aspects, the gap 109 has a width of at least 0.5 cm. In other aspects, the gap 109 has a width of at least 1 cm. In other aspects, the gap 109 has a width of at least 1.5 cm. In some aspects, the gap 109 has a width between 0.5 cm and 1.5 cm. In other aspects, the gap 109 has a width of at least 2 cm. In other aspects, the gap 109 has a width between 2 cm and 2.5 cm. In other aspects, the gap 109 has a width of at least 2.5 cm.

[0193] like Figure 9B As shown, seal 107 is laminated onto membrane 113, and further laminated onto each other as seal 108. Figure 7 As shown, the lamination of the bonding layer 105 can be completed in two steps: first, lamination is applied to individual films 113, and then a second step joins the pre-laminated films 113 together. Alternatively, the lamination steps can be combined into a single step, where a single bonding layer 105 is used to join the films together.

[0194] like Figure 9B As shown, seal 107 can extend beyond the width of seal 108. By extending seal 107 beyond the width of seal 108, seal 107 provides reinforcement at flexural point 115, as... Figure 9A As shown. Not limited to a specific mechanism, it is believed that the bonding layer 105 serves as a reinforcing strain relief device inside the seal and allows the bag to flex at the seal as it is filled and discharged with blood products.

[0195] This disclosure provides and includes a collapsible blood container 102 having geometric features that improve blood mixing during the deoxygenation process. The improved geometry of this disclosure also includes geometry that enhances the filling and discharging of the collapsible blood container 102. The improved geometry can reduce or eliminate 'dead corners' in the bag. Without being theoretically limited, dead corners occur at the corners of a bag with a square geometry. Prior to this disclosure, methods and blood consumption devices were not time-limited, and the commonly used gas exchange methods resulted in adequate mixing. Therefore, the shortcomings of earlier designs were not disclosed.

[0196] According to aspects of this disclosure, the collapsible blood container 102 includes one or more geometric features 121. In one aspect, the geometric features include rounded corners in the collapsible blood container 102 and provide "dead corner" elimination during integration. This disclosure provides geometric features 121 to be directly incorporated into the bonding layer 105. In other aspects, the geometric features 121 can be incorporated into the collapsible blood container 102 using an external mold or plate. In still other aspects, the geometric features of the collapsible blood container 102 can be provided by a suitable mold having the shape of the geometric features 121. In some aspects, the geometric features 121 are provided to the collapsible blood container 102 in a circular or elliptical shape, as shown, for example, in FIG. 10.

[0197] In some aspects, the geometric feature 121 may be an ellipse having a first radius of about 0.1 cm to about 7.6 cm and a second radius of about 1 cm to about 7.6 cm. In one aspect, the geometric feature 121 may be an ellipse having a first radius of about 2.5 cm and a second radius of about 5 cm. In another aspect, the geometric feature 121 may be an ellipse having a first radius of about 5 cm and a second radius of about 7.6 cm. In another aspect, the geometric feature 121 may be a circle having a diameter of about 5 cm. In another aspect, the geometric feature 121 may be a circle having a diameter of about 7.6 cm.

[0198] It is evident that the oxygen consumption device 10, with its defined dimensions, necessarily constrains the size of the collapsible blood container 102 according to this disclosure. In some respects, the collapsible blood container 102 is also limited by a specified surface-to-volume ratio. Based on these limitations, this disclosure provides and includes a collapsible blood container 102 having two or more chambers in fluid communication with each other.

[0199] Oxygen-consuming container devices can be constructed in such a way that the blood volume to bag area ratio is optimized relative to the overall size of the oxygen-consuming container device, while exposing more blood volume to an oxygen-permeable material within the utilized space. The blood volume can be contained in a collapsible blood container 102 having two or more chambers, which allow for specific arrangement within an external receiver 101. In some respects, the height of the oxygen-consuming device 10 does not occupy impractical space in the intended mixing apparatus when placed on a surface. These chambers can be arranged from side to side, stacked vertically on top of each other, partially stacked on top of each other, staggered in a row, or mounted vertically on top of each other at one or more stack heights. Adsorbent 103 can be positioned as needed above or between the chambers. When such chambers are connected via fittings or fluid conduits that allow for easy filling and discharging, the chambers can be filled and discharged individually or concurrently. It should be understood that the arrangement and interconnection of the collapsible blood containers 102 having two or more chambers can be performed by those skilled in the art.

[0200] In some respects, the collapsible blood container 102 includes two or more chambers. On one hand, the collapsible blood container 102 may have two chambers arranged side-by-side or end-to-end, depending on size. On another hand, the collapsible blood container 102 may have three chambers arranged side-by-side or end-to-end, depending on size. And yet another hand, the collapsible blood container 102 may have three chambers arranged side-by-side or end-to-end, depending on size. Those skilled in the art can prepare other configurations of the collapsible blood container 102 having multiple chambers placed in adjacent positions and orientations to maximize space utilization.

[0201] In other aspects provided and included in this disclosure, the collapsible blood container 102 may include two or more stacked chambers. When in a stacked configuration, spacers 110 or mesh 110 are included to ensure separation of adjacent chambers in order to maintain optimal gas diffusion rates. In some aspects, the space between the stacked chambers may also include one or more adsorbent pouches to maintain optimal gas diffusion rates. In some aspects, two chambers may be stacked. In another aspect, three chambers may be stacked. In yet another aspect, four chambers may be stacked.

[0202] This disclosure provides and includes a collapsible blood container 102 comprising a combination of stacked and adjacent chambers. As provided herein, the number and stacking of the chambers in the collapsible blood container 102 also include at least 0.4 cm. 2 / ml surface area to volume ratio of the combined chamber. Further variations consistent with this disclosure can be prepared by those skilled in the art.

[0203] This disclosure provides and includes an oxygen-consuming device 10 for consuming oxygen from blood, comprising a substantially oxygen-impermeable external receiver 101, an oxygen-impermeable internal collapsible blood container 102, and an oxygen adsorbent located within the external receiver, wherein the collapsible blood container 102 further includes one or more mixing structures 119 that increase blood mixing during oxygen consumption. In some aspects, the mixing structure 119 is incorporated into the structure of the collapsible blood container 102. In other aspects, the mixing structure 119 is incorporated into the interior of the collapsible blood container 102 rather than being physically attached to it. In still other aspects, the mixing structure 119 is an external structure of the collapsible blood container 102 that restricts or modifies the shape of the container 102 to reduce or disrupt laminar flow. The mixing structure 119 according to this disclosure is designed to increase blood movement within the collapsible blood container 102, increase turbulence within the collapsible blood container 102, or a combination of both. Importantly, the mixing structure and mixing should not significantly increase the lysis or damage of red blood cells.

[0204] According to aspects of this disclosure, a hybrid structure 119 is included in the structure of membrane 113. In some aspects, the hybrid structure 119 in membrane 113 includes ridges, protrusions, or projections on the interior of the collapsible blood container 102 and is in contact with blood. In one aspect, the hybrid structure 119 in membrane 113 includes one or more ridges. In another aspect, the hybrid structure 119 includes connecting the upper membrane 113 and the lower membrane 114 together, for example as... Figure 10C and 10D As shown. In one aspect, one or more ridges extend across the entire width or length of the inner surface of the collapsible blood container 102. In other aspects, the ridges alternate and may intersect. In some aspects, the mixing structure 119 in membrane 113 includes protrusions or other protrusions designed to disrupt laminar flow and induce turbulence. Similarly, in some aspects, the mixing structure 119 in membrane 113 includes recesses designed to disrupt laminar flow and induce turbulence. In some aspects, the mixing structure 119 is a baffle incorporated into membrane 113. The baffle is a guide vane or panel. In some aspects, the mixing structure 119 including one or more baffles may be incorporated into a second membrane 114.

[0205] In some respects, a mixing structure 119 is included within the collapsible blood container 102. In one aspect, the mixing structure 119 within the collapsible blood container 102 includes one or more small beads or spheres that facilitate mixing when the collapsible blood container 102 is agitated. In another aspect, the mixing structure 119 within the collapsible blood container 102 includes one or more thin strings or elongated structures that facilitate mixing when the collapsible blood container 102 is agitated. In yet another aspect, the mixing structure 119 within the collapsible blood container 102 includes a mesh that facilitates mixing when the collapsible blood container 102 is agitated.

[0206] This disclosure provides and includes an oxygen-consuming device 10 having an external receiver 101 that is substantially oxygen-impermeable, thereby sealing an internal collapsible blood container 102 and providing a top space. In one aspect, an oxygen adsorbent 103 is disposed within the top space, thereby creating an oxygen-consuming state within the top space. In another aspect, the oxygen adsorbent 103 disposed in the top space further maintains the top space in an oxygen-consuming state by removing oxygen that may enter through the external receiver 101 or through one or more inlets / outlets 30.

[0207] Maintaining the headspace in an oxygen-consuming state provides an improved lifespan for the oxygen-consuming device 10. In one aspect, the assembled oxygen-consuming device 10 has a lifespan of at least 24 months. In another aspect, the oxygen-consuming device 10 has a lifespan of at least 12 months after component assembly. According to one aspect of this disclosure, the assembled oxygen-consuming device 10 conforms to the 1STA-2A standard.

[0208] In some aspects of this disclosure, the headspace provides improved processing time. For the oxygen consumption device 10, removing ambient air or inert purging gas from the assembly before sealing the external receiver 101 reduces the headspace volume. Applying a vacuum to the external receiver 101 before sealing reduces the headspace volume and decreases the overall volume of the assembled oxygen consumption device. While the reduced overall headspace volume provides a reduced transport volume, constraining the collapsible blood container 102 can result in an increased filling time. In some aspects, the headspace can be purged with nitrogen and then sealed at slightly below ambient pressure to provide a reduced headspace volume in the oxygen consumption device 10 without significantly increasing filling and processing time.

[0209] In some respects, the headspace can initially be used to consume oxygen by purging it with nitrogen. In one respect, the headspace of the oxygen consumption device 10 is purged with nitrogen before sealing the external receiver 101. In another respect, the purging gas is nitrogen with a purity of ≥99.9%.

[0210] This disclosure includes and provides an oxygen consumption device 10 having an internal collapsible blood container 102 divided into two or more compartments. In some aspects, the headspace of the oxygen consumption device 10 having the collapsible blood container 102 divided into multiple compartments is between 10 ml and 500 ml per compartment. In one aspect, the headspace is between 20 ml and 400 ml per compartment. In another aspect, the headspace volume is between 60 ml and 300 ml per compartment. In another aspect, the headspace volume is between 100 ml and 200 ml per compartment of the collapsible blood container. In one aspect, the headspace of the oxygen consumption device 10 having the internal collapsible blood container 102 divided into compartments is approximately 10 ml per compartment. In another aspect, the headspace is approximately 100 ml to approximately 200 ml per compartment. In another aspect, the headspace is approximately 300 ml to approximately 500 ml per compartment.

[0211] This disclosure includes and provides an oxygen consumption device 10 having an internal collapsible blood container 102 divided into two or more compartments. In some aspects, the headspace of the oxygen consumption device 10 having the collapsible blood container 102 divided into two compartments is between 20 ml and 1000 ml. In another aspect, the headspace is between 100 ml and 800 ml. In another aspect, the headspace volume is between 200 ml and 700 ml. In another aspect, for a two-compartment collapsible blood container, the headspace volume is between 300 ml and 500 ml. In one aspect, the headspace of the oxygen consumption device 10 having the internal collapsible blood container 102 divided into two compartments is about 700 ml. In another aspect, the headspace is about 200 ml to about 700 ml. In another aspect, the headspace is about 300 ml to about 500 ml.

[0212] This disclosure includes and provides an oxygen consumption device 10 having an internal collapsible blood container 102 divided into two or more compartments. In some aspects, the headspace of the oxygen consumption device 10 having a collapsible blood container 102 divided into three compartments is between 20 ml and 1000 ml. In one aspect, the headspace is between 100 ml and 800 ml. In another aspect, the headspace volume is between 200 ml and 700 ml. In another aspect, for a three-compartment collapsible blood container, the headspace volume is between 400 ml and 600 ml. In one aspect, the headspace of the oxygen consumption device 10 having an internal collapsible blood container 102 divided into three compartments is approximately 800 ml. In another aspect, the headspace is approximately 200 ml to approximately 700 ml. In another aspect, the headspace is approximately 400 ml to approximately 600 ml. In one aspect, due to sufficient expansion of the headspace region, the headspace is approximately 7000 ml. In another aspect, the headspace is between 700 ml and 7000 ml. On the other hand, the headroom is between 800ml and 6000ml. On another hand, the headroom is between 1000ml and 5000ml. On yet another hand, the headroom is between 2000ml and 4000ml.

[0213] This disclosure includes and provides an oxygen consumption device 10 having an internal collapsible blood container 102 and further including one or more spacers 110, said one or more spacers 110 ensuring separation between an external receiver 101 and the internal collapsible blood container 102. The spacers 110 provide headspace within the oxygen consumption device to ensure efficient diffusion of oxygen from the surface of the membrane 113 to the adsorbent 103. The spacers 110 may be made of one or more materials selected from the group consisting of: mesh, molded pad, woven pad, nonwoven pad, stranded yarn, and stranded pad. In some aspects, the spacers 110 may be directly integrated into the collapsible blood container 102 as a rib, recess, or other protruding feature capable of maintaining separation between the external receiver 101 and the internal collapsible blood container 102. This specification also includes and provides spacers 110 integrated into the external receiver 101 as a rib, recess, or other suitable protruding feature capable of maintaining separation between the external receiver 101 and the internal collapsible blood container 102. Hybridization is an important aspect of this disclosure. In one aspect of this disclosure, the spacer 110 is selected to be flexible so as not to interfere with the flow of blood products.

[0214] This disclosure includes and provides a spacer 110 having open areas for free diffusion of gas from the surfaces of permeable membranes 113 and 114. In one aspect, the spacer 110 is provided as a mesh 110 having open spaces 111. As used herein, the open spaces 111 are also referred to as slits 111. As provided herein, slits 111 can be provided by a regular weave of the mesh 110, such that slits 111 are regular and repeat within the spacer 110. In other aspects, slits 111 can include irregular open areas, such as those provided by a spacer 110 constructed of a nonwoven mesh. In one aspect, the area of ​​slits 111 is approximately 0.5 mm. 2 (mm 2 ) and approximately 100mm 2 Between. On the other hand, the area of ​​gap 111 is 1 mm. 2 With 10mm 2 Between. In other respects, slit 111 has each opening greater than 0.75 mm. 2 The openings. In one aspect, the open areas or gaps of the mesh occupy between 30% and 90% of the total area of ​​the spacer 110. In another aspect, the open areas or gaps of the mesh occupy between 50% and 80% of the total area of ​​the spacer 110. In yet another aspect, the open areas occupy approximately 60%. In still other aspects, the open areas occupy up to 75% of the total area.

[0215] This disclosure provides and includes an internal collapsible blood container 102 having a spacer 110 incorporated into a membrane 113, membrane 114, or both. According to an aspect of this disclosure, the spacer 110 provides separation of the external receiver 101 from the internal collapsible blood container 102 and also provides reinforcement of the permeable membrane. According to an aspect of this disclosure, the spacer 110 prevents tearing, puncture, and rupture of the internal collapsible blood container 102 when filled with blood and used in the consumption method of this disclosure. In some aspects, the spacer 110 is provided as a mesh 110 integrated into a siloxane membrane during the manufacturing process. In other aspects, the spacer 110 is applied to and attached to a finished siloxane membrane. In still other aspects, the spacer 110 is provided as an integrated porous membrane mesh.

[0216] In one aspect, a membrane 113 or 114 having integrated spacers 110 is prepared from a suspension of liquid siloxane rubber (LSR). In another aspect, the LSR is suspended in xylene, hexane, tert-butyl acetate, heptane, acetone, or naphtha. In accordance with an aspect of this disclosure, the suspension contains 10% to 30% LSR. As provided herein, the membrane 113 or 114 having integrated spacers 110 is prepared by providing an LSR suspension layer of 20 μm to 750 μm, partially curing the LSR layer and applying spacers 110 as provided in this disclosure, and performing a second curing step to provide a cured siloxane membrane 113 of 10 μm to 100 μm thickness having integrated spacers 110.

[0217] This disclosure also includes and provides a mesh 110 comprising co-extruded fibers having an inner material 117 and a bonding material 118. According to an aspect of this disclosure, during the application of the mesh 110 to a membrane, the bonding material 118 is integrated into the pores of the membrane 113 (114). In one aspect, the bonding material 118 is integrated into the pores of the porous membrane 113 by heating. According to an aspect of this disclosure, the bonding material 118 may be selected from the group consisting of ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), or acrylate. According to an aspect of this disclosure, the co-extruded fibers having the inner material 117 and the bonding material 118 are DuPont fibers comprising modified ethylene vinyl acetate and modified ethylene ethyl acrylate. The series of meshes 110.

[0218] This disclosure also includes and provides an internal collapsible blood container 102 that includes a window 112. As used herein, the window 112 is made of a transparent material and is glued or otherwise incorporated into the internal collapsible blood container 102. According to this disclosure, a suitable material for the window 112 is blood-compatible. In some respects, the material suitable for the window 112 is oxygen-impermeable. In other respects, the material suitable for the window 112 is oxygen-impermeable. The size of the window 112 only needs to be large enough to provide observation of the blood.

[0219] This disclosure also includes and provides a collapsible blood container having di(2-ethylhexyl) phthalate (DEHP). DEHP is included as a plasticizer in most PVC-based blood storage bags, where it has been observed to provide protection for stored red blood cells. See U.S. Patent 4,386,069 to Estep. In some aspects, the oxygen consumption device 10 may also include DEHP incorporated into the internal collapsible blood container 102. In other aspects, DEHP may be provided separately within the internal collapsible blood container 102.

[0220] This disclosure provides and includes an oxygen-consuming device 10 excluding DEHP. It is assumed that DEHP can be used as an endocrine disruptor, and some regulatory agencies are considering ordering the removal of DEHP from blood bags. It has been observed that DEHP may not be necessary when storing red blood cells anaerobically. See International Patent Publication No. WO 2014 / 134503, which is incorporated herein by reference in its entirety. Thus, in some aspects, the oxygen-consuming device 10 completely excludes DEHP from all blood-contact surfaces. In other aspects, the oxygen-consuming device 10 limits DEHP-containing surfaces to fittings, ports, and inlets, such as those shown in the figures, for example, 106 and 205. In one aspect, the oxygen-consuming device 10 excludes the collapsible blood container 102 containing DEHP.

[0221] This disclosure provides and includes an oxygen consumption device 10 having an oxygen indicator 104. Similarly, this disclosure provides and includes a blood storage device 20 having an oxygen indicator 206. In one aspect, the oxygen indicator 206 detects oxygen and indicates that the oxygen consumption device 10 has been damaged and is no longer suitable for its intended purpose. In another aspect, the oxygen indicator 206 provides a visual indication of the presence of oxygen. In some aspects, the oxygen indicator 206 provides an indication of the amount of oxygen.

[0222] According to one aspect of this disclosure, the external receiver may contain an oxygen indicator to notify the user whether the oxygen adsorbent is no longer effective for any reason (such as lifespan) or whether the external receiver has been damaged, allowing excessive oxygen to enter from the ambient air. Such oxygen indicators are readily available and are based on a methylene blue indicator dye, which turns blue in the presence of about 0.5% or higher oxygen and pink when the oxygen level is below about 0.1%. Examples of these oxygen indicators are Tell-Tab oxygen indicator tablets from Sorbent Systems, Inc. (Impak Corp., Los Angeles, CA) and oxygen indicator tablets from Mitsubishi Gas Chemical America (MGCA, NY, NY).

[0223] This disclosure provides and includes a method for preparing blood for storage under oxygen-depleting conditions, the method comprising supplying blood containing red blood cells to an oxygen-depleting device 10, the blood having oxygen to be removed, incubating the blood for a certain period of time, and transferring the deoxygenated blood to an anaerobic storage bag. According to an aspect of this disclosure, the method further includes agitating the oxygen-depleting device 10 to provide mixing of the deoxygenated blood. In other aspects, agitation is not necessary due to the configuration of the oxygen-depleting device 10.

[0224] For safety reasons, the collection and processing of blood are regulated by national or regional government agencies. In the United States, the Food and Drug Administration (FDA) has developed guidelines for the proper handling of blood and blood products. Similarly, in Europe, the European Union has regulatory bodies that are binding on member states and generally follow guidelines provided by the European Commission. For example, key requirements for blood companies and hospital blood banks in the United Kingdom (UK) are defined in Blood Safety and Quality Management (Statute No. 50 2005), and are enforced by the Medicines and Healthcare products Regulatory Agency (MHRA), which derives its power from UK legislation, to maintain the safety and quality of blood and blood product transfusions in the UK.

[0225] Generally, guidelines developed by various institutions fall into two main groups. In the first group, exemplified by the United States, the permissible timeframe from donor collection to platelet processing, thereby driving RBC storage at 2°C to 6°C, is 8 hours. That is, the various processing steps currently involved, including plasma separation and collection, leukopenia, platelet separation and collection, and compressed red blood cell preparation, must be completed within 8 hours, and the various components must be stored to preserve platelet viability (see Moroff & Holme, “Concepts about current conditions for the preparation and storage of platelets” in Transfus Med Rev 1991; 5: 48-59). In Europe, the available timeframe for processing is 24 hours. Therefore, the methods and processes provided in this disclosure are designed to achieve beneficial and stored blood with reduced deoxygenation levels within approximately 8 hours of venipuncture.

[0226] According to the method of this disclosure, blood can be obtained from a donor and processed to an oxygen saturation of less than 20% within 12 hours of collection. Consumption processing begins at or shortly after collection, improving processing efficiency by utilizing the increased reaction rate due to higher temperatures. In one aspect, blood is collected from the donor at approximately 37°C and collected in an oxygen consumption device 10 containing a suitable amount of anticoagulant. In addition to the elevated temperature, whole blood typically has an oxygen saturation of approximately 35%-65% when collected from a patient via venipuncture. In one aspect of this disclosure, whole blood has an oxygen saturation of 35%-65% when collected from a patient via venipuncture. In another aspect, whole blood has an oxygen saturation of 40%-60% when collected from a patient via venipuncture. In another aspect, whole blood has an oxygen saturation of 45%-55% when collected from a patient via venipuncture. In another aspect, whole blood has an oxygen saturation of 50%-65% when collected from a patient via venipuncture. Conventional methods do not provide collection kits and bags to prevent oxygen from entering. Therefore, delays in initiating the oxygen reduction process can significantly increase the time required to prepare oxygen-reduced blood with less than 20% oxygen saturation.

[0227] The methods and apparatus disclosed herein also provide for the preparation of oxygen-depleted blood with an oxygen saturation of less than 10%. In one aspect, the 10% level is achieved within 8 hours or less of collection from a donor. In another aspect, the blood is reduced to an oxygen saturation of less than 10% within 6 hours or less. In yet another aspect, the blood is reduced to an oxygen saturation of less than 10% within 4 hours or less.

[0228] As used herein, the term "blood" refers to whole blood, leukopenic RBCs, thrombocytopenic RBCs, and RBCs with both leukopenia and thrombocytopenia. The term blood also includes compressed red blood cells, thrombocytopenic compressed red blood cells, leukopenic compressed red blood cells (LRpRBCs), and compressed red blood cells with both leukopenia and thrombocytopenia. The temperature of blood can vary depending on the stage of the collection process, starting at a normal body temperature of 37°C at the time and place of collection, but rapidly decreasing to approximately 30°C once the blood leaves the patient's body, and further decreasing to room temperature over approximately 6 hours without processing, and finally being refrigerated between approximately 2°C and 6°C.

[0229] As used in this article, the term "whole blood" refers to a suspension of blood cells containing red blood cells (RBCs), white blood cells (WBCs), and platelets suspended in plasma, and also includes electrolytes, hormones, vitamins, antibodies, etc. In whole blood, the normal number of white blood cells is 4.5 x 10⁻⁶. 9 With 11.0x10 9 The normal RBC range at sea level is 4.6–6.2 x 10^9 cells / L for males. 12 / L, and for women it is 4.2-5.4x10 12 / L. Normal hematocrit percentage is approximately 40%-54% in men and 38%-47% in women. Platelet counts are typically 150-450 x 10^6 / L in both men and women. 9 / L. Whole blood is collected from a blood donor and is typically in combination with an anticoagulant. Whole blood is initially collected at about 37°C and rapidly cooled to about 30°C during and shortly after collection, but slowly cooled to ambient temperature over about 6 hours. According to the methods of this disclosure, whole blood collection can be initiated at 30-37°C or room temperature (typically about 25°C). As used herein, one “unit” of blood is about 450-500 ml, including the anticoagulant.

[0230] As used herein, a “blood donor” is a healthy individual from whom whole blood is typically collected via venipuncture or intravenous puncture, wherein the donated blood is processed and stored in a blood bank for later use by a recipient different from the donor. A blood donor may be a subject scheduled for surgery or other treatment, who may donate blood to themselves in a process known as autologous blood donation. Alternatively and most commonly, blood is donated for use by another person in a process known as heterologous transfusion. The collection of whole blood samples from a donor, or in the case of autologous transfusion, can be accomplished using techniques known in the art, such as by blood donation or apheresis. Whole blood obtained from a donor using venipuncture has an oxygen saturation (sO2) in the range of approximately 30% to approximately 70%.

[0231] As used herein, “red blood cells” (RBCs) include RBCs present in whole blood, RBCs with leukopenia, RBCs with thrombocytopenia, and RBCs with both leukopenia and thrombocytopenia. Human red blood cells are in a dynamic state within the body. Red blood cells contain hemoglobin, an iron-containing protein that carries oxygen throughout the body and gives blood its color. The percentage of blood volume composed of red blood cells is called hematocrit. As used herein, unless otherwise specified, RBCs also include compressed red blood cells (pRBCs). Compressed red blood cells are prepared from whole blood using centrifugation techniques commonly known in the art. As used herein, unless otherwise specified, pRBCs have a hematocrit of approximately 50%.

[0232] Platelets are small cellular components of blood that facilitate the clotting process by adhering to the lining of blood vessels and also promote healing by releasing growth factors upon activation. Like red blood cells, platelets are produced in the bone marrow and survive in the circulatory system for 9-10 days before being removed by the spleen. Platelets are typically prepared using a centrifuge to separate them from the erythrocyte sedimentation rate (ESR) layer sandwiched between the plasma layer and red blood cell granules.

[0233] Plasma is a protein salt solution and the liquid portion of blood in which red blood cells, white blood cells, and platelets are suspended. Plasma is 90% water and makes up about 55% of blood volume. One of the main functions of plasma is to assist in blood clotting and immunity. Plasma is obtained by separating the liquid portion of blood from the cells. Typically, plasma is separated from cells by centrifugation. Centrifugation is a process used to separate the components of whole blood into plasma, white blood cells, platelets, and compressed red blood cells. During centrifugation, the plasma initially migrates to the top of the vessel during a gentle spin. The plasma is then removed from the vessel. White blood cells and platelets are removed during a second centrifugation cycle to produce compressed red blood cells.

[0234] This disclosure includes and provides a method for preparing oxygen-depleted blood for storage. The oxygen-depleted blood or blood component suitable for storage and benefiting from reduced storage lesion damage, reduced toxicity, and significantly reduced morbidity is blood or blood component with an oxygen saturation of less than about 20%. In some aspects, the oxygen level in the blood or blood component is reduced to less than 15%. In other aspects, the oxygen saturation of the blood is reduced to 10% or less prior to storage. In yet another aspect, the oxygen saturation of the blood is reduced to less than 5% or less than 3% prior to storage.

[0235] According to the method of this disclosure, blood or blood components are oxygenated and placed in a storage container within 4 to 24 hours after collection. In another aspect, the method provides oxygenation within 8 hours after collection and placement in a storage container. In yet another aspect, blood or blood components are oxygenated and placed in a storage container within less than 6 hours of collection. And still another aspect, blood is oxygenated and placed in a storage container within less than 4 hours of collection.

[0236] This disclosure provides and includes a method for preparing blood for storage under oxygen-depleting conditions, the method comprising supplying blood containing red blood cells to an oxygen-depleting device 10, the blood having oxygen to be removed, and incubating the blood for a certain period of time. In some aspects, the blood is mixed by agitation. In other aspects, the oxygen-depleting device provides sufficient deoxygenation, and mixing is minimal or nonexistent.

[0237] As will be understood, the blood used for consumption can begin at varying levels of oxygen saturation. In some respects, the blood is whole blood collected with a saturation of about 70% and a hematocrit between about 40% and 45%. The method disclosed herein also provides rapid deoxygenation of LRpRBCs typically having a hematocrit of about 50% and a saturation level of up to 90% or higher.

[0238] The apparatus and methods of this disclosure are intended to provide oxygen-consuming blood for storage for 24 hours or less. In some aspects, oxygen is removed using the oxygen-consuming device 10 by incubation under agitation for a certain period of time. In other aspects, oxygen is removed using the oxygen-consuming device 10 by means of methods in which the consuming device is not agitated or otherwise mixed during incubation. As those skilled in the art will understand, including an agitation or mixing step in the process allows the oxygen-consuming device 10 to have a low surface-to-volume ratio. Agitation can also reduce the permeability necessary to achieve the desired level of deoxygenation. To achieve the fastest consumption kinetics, a combination of the oxygen-consuming device 10 with high permeability and a high surface-to-volume ratio is combined with agitation during consumption. Depending on the application and processing scheme employed, the time required to complete the processing can vary between 4 and 24 hours. Therefore, the apparatus and methods of this disclosure can be incorporated into existing blood processing center schemes and comply with applicable regional regulations by adapting the apparatus and methods provided as disclosed herein.

[0239] In accordance with this disclosure, to reduce the processing time to achieve a blood saturation of less than 20%, the blood may be agitated or mixed during consumption. In most cases, the blood is agitated or mixed for less than 24 hours. Since mixing and agitation of the blood during processing can lead to lysis and degradation, the consumption time under agitation conditions should be minimized.

[0240] In some aspects, the blood is incubated under agitation for less than 12 hours. In other aspects, the incubation and agitation time is less than 8 hours. A method is also provided for reducing oxygen to less than 20% using the oxygen-consuming device 10 and incubating under agitation for less than 6 hours or less than 4 hours. In yet another aspect, the incubation time under agitation is 3.5 hours or 3.0 hours. In some aspects, blood can be restored to 20% or less by incubating under agitation in the oxygen-consuming device 10 for 4 hours. In yet another aspect, the method provides an incubation time of 0.5 or 1.0 hours. In other aspects, the blood is incubated in the oxygen-consuming device 10 for 1.5 hours or 2.0 hours.

[0241] It is fully understood that the reaction rate is temperature-dependent, with higher temperatures increasing the reaction rate. The rate constant k changes exponentially with temperature, where k = Ae^(-π / 2). Ea / RT (Arrhenius equation). It is noteworthy that the temperature dependence is independent of the reactant concentration and whether the rate order is constant (e.g., first-order versus second-order). Typically, an increase in temperature of 10°C can result in a doubling of the reaction rate. Therefore, those skilled in the art will recognize that the release of oxygen from hemoglobin and other steps in the deoxygenation process are temperature-dependent. Importantly, the deoxygenation rate decreases significantly once the blood temperature drops to a standard storage temperature between 2°C and 6°C. Furthermore, under the conditions of currently approved protocols for the collection, processing, and storage of blood for transfusion purposes, the stored blood is not mixed, which further reduces the rate at which oxygen can be removed. Therefore, the methods and apparatus of this disclosure are designed to remove the majority of oxygen prior to storage and within a time period established by appropriate regulatory authorities. As provided herein, oxygen consumption is intended to begin as soon as possible after donor collection and is intended to be largely completed before the blood intended for storage cools.

[0242] As provided herein, the method can be performed using recently collected blood at approximately 37°C at the time of collection from the donor. In other respects, the blood may be processed prior to consumption, including the removal of leukocytes, plasma, and platelets. Alternatively, the blood may be further processed after oxygen depletion.

[0243] This disclosure provides and includes the treatment of blood that has been cooled from body temperature to ambient temperature (typically about 25°C). Using the methods and apparatus disclosed herein, oxygen-reduced blood with an oxygen saturation of less than 20% can be prepared at ambient temperature (e.g., about 25°C). The ability to reduce oxygen to a desired and beneficial level at ambient temperature allows the systems and methods to be incorporated into existing blood collection protocols and blood collection centers.

[0244] This disclosure provides and includes a method for preparing blood for storage under oxygen-consuming conditions, the method comprising supplying blood containing red blood cells to an oxygen-consuming device 10, the blood having oxygen to be removed, incubating the blood for a certain period of time, and further comprising agitating or mixing during the incubation period. As used herein, the terms “agitation” and “mixing” are used interchangeably and include a variety of mixing methods, including but not limited to shaking, nutation, rotation, stirring, kneading, oscillation, linear oscillation, and compression of the oxygen-consuming device.

[0245] In the method according to this disclosure, the incubation period under agitation can be as short as 30 minutes and as long as 24 hours. In some aspects, the method includes an incubation period of 1 to 3 hours under agitation in the oxygen-consuming device 10. In other aspects, the incubation period is between 1 and 4 hours or between 1 and 6 hours. In still other aspects, the incubation period is about 2 hours or about 4 hours.

[0246] According to one aspect of this disclosure, a method for reducing oxygen from red blood cells includes placing the red blood cells in an apparatus according to this disclosure and placing the apparatus on an agitator to enhance the removal of oxygen from the red blood cells through mixing. The use of agitators in transfusion practice is well known in relation to preventing clot formation, such as the use of shakers and donation scale mixers, which provide a gentle shaking motion with an inclination of about 7 degrees and an oscillation rate of about 1 to 15 times per minute. Similar devices already available in oxygen consumption centers and familiar to staff can be used to ensure proper mixing.

[0247] To maximize the kinetics of oxygen depletion, physical and methodological approaches can be applied. As discussed above, physical approaches to reducing diffusion resistance in the internal blood-compatible bag include selecting highly permeable materials and decreasing the material thickness to lower the Barre value. For microporous materials, the apparent Barre value can be reduced by decreasing the size of the micropores and by increasing the number of micropores. It should be understood that the size of the micropores must be adequately limited to prevent water percolation through the barrier layer, which is present in some microporous materials of approximately 1 μm. Similarly, as provided above, the surface-to-volume ratio is selected to reduce the diffusion lag of dissolved oxygen as it enters the permeable surface. The limitations and requirements of these materials and designs for achieving efficient and rapid reduction of oxygen in the blood have been discussed above.

[0248] In addition to minimizing the diffusion barrier layer and diffusion distance through design and appropriate material selection, the effective diffusion distance can be further reduced through proper mixing. As will be understood, complete and efficient mixing effectively eliminates the effect of diffusion distance on the blood reduction process as oxygenated red blood cells enter the anaerobic environment near the permeable membrane. Similarly, diffusion distance will also be eliminated by spreading the blood into an impractical thin volume. This disclosure provides methods and apparatus for optimizing the aforementioned apparatus and methods to achieve high consumption rates.

[0249] This disclosure provides and includes a method for mixing blood in an oxygen-consuming device 10, the method achieving a rapid deoxygenation rate and within approximately 0.5 x 10⁻⁶. -2 minute -1 With approximately 5.0 x 10 -2 minute -1 The rate constant is between [a certain value]. According to an aspect of this disclosure, the rate constant is at least 1.28 x 10⁻⁶. -2 minute -1 In other respects, deoxygenation occurs at a rate constant of at least -0.5 x 10⁻⁶. -2 The rate of deoxygenation occurs. On the other hand, deoxygenation occurs at a rate constant of at least -0.9 x 10⁻⁶. -2 The rate of deoxygenation occurs. On the other hand, deoxygenation occurs at a rate constant of at least -1.0 x 10⁻⁶. -2The rate of deoxygenation occurs. On the other hand, deoxygenation occurs at a rate constant of at least -1.5 x 10⁻⁶. -2 The rate of deoxygenation occurs. In another respect, deoxygenation occurs at a rate constant of -1.0 x 10⁻⁶. -2 minute -1 With -3.0x10 -2 minute -1 The rate between these two points occurs. In another aspect, deoxygenation occurs at a rate constant of -1.0 x 10⁻⁶. -2 minute -1 With -2.0x10 -2 minute -1 The rate between these two points occurs. In another aspect, deoxygenation occurs at a rate constant of -1.0 x 10⁻⁶. -2 minute -1 With -4.0x10 -2 minute -1 The rates between them occur.

[0250] According to one aspect of this disclosure, the surface-to-volume ratio is at least 5.0 cm². 2 Proper mixing is achieved in the oxygen-consuming device 10 with a volumetric oxygen consumption of / ml. Without being bound by theory, it is assumed that at a low surface-to-volume ratio, the collapsible blood container does not have sufficient capacity to allow blood movement and mixing does not occur. It should be understood that a bag filled to a volume similar to that of a blood-sucking tick will be substantially difficult to mix and will not readily induce convection or other flows. In other words, an internal collapsible container 102 filled to a volume where the flexibility of the bag material decreases beyond its capacity to generate during agitation results in substantially no mixing. Therefore, by selecting a minimum of 4.85 cm... 2 A surface-to-volume ratio of / ml allows for mixing when blood is 'swirled' from side to side. It should be understood that inappropriate mixing leads to undesirable hemolysis of red blood cells. Therefore, there are practical limits to mixing. This disclosure provides apparatus and methods for achieving significant mixing while reducing potential hemolysis.

[0251] According to one aspect of this disclosure, a method for reducing oxygen from red blood cells includes placing the red blood cells in an apparatus according to this disclosure and placing the apparatus on an agitator to enhance the removal of oxygen from the red blood cells. The use of agitators in transfusion practice is well known in relation to preventing clot formation, such as shakers and donation-type mixers used when used with whole blood and red blood cell suspensions, and also when used for platelet storage, where platelets require oxygen for survival, and agitation to prevent platelet aggregation and activation.

[0252] Regarding currently available devices for agitating red blood cells (whether whole blood or other red blood cell suspensions), the platform typically rotates a few degrees around a central axis to provide a slight agitation, and many commercially available options exist. For example, the Bellco Glass model #7740-10000 (Bellco Glass, Inc., Vineland, NJ) offers a 7-degree tilt and 1 to approximately 12 oscillations per minute. The Medicus Health model 5277M5 nutation mixer (Medicus Health, Kentwood, MI) provides a 20-degree tilt for red blood cell suspension samples at 24 rpm. Another style of device used to prevent whole blood clotting during blood donation is the Genesis blood collection mixer model CM735A (GenesisBPS, Ramsey, NJ), which provides approximately 20 degrees of tilt and performs 3 cycles in approximately 3 seconds, then rests for approximately 2 seconds to weigh the sample and repeats until the desired weight is achieved. The Benchmark Scientific B3D2300 (BenchmarkScientific, Inc., Edison, NJ) offers a variable tilt angle of 0-30 degrees and 2-30 oscillations per minute.

[0253] This disclosure also includes and provides other available means of agitating blood samples, including orbital oscillators, such as the LOS-101 from Labocon (Labocon Systems, Ltd, Hampshire, UK) with a displacement of 20 mm and an oscillation rate of 20-240 rpm, or the EW-51820-40 from Cole-Parmer (Cole-Parmer, Inc., Vernon Hills, IL) with a displacement of 20 mm and an oscillation rate of 50-250 rpm.

[0254] Devices for agitating platelets are also well known in the art and include various models, such as the PF96h from Helmer Scientific (Helmer Scientific, Noblesville, IN), which provides approximately 70 cycles / min of linear oscillation and approximately 38 mm (1.5 inches) of displacement, and the PAI200 from Terumo Penpol (Terumo Penpol Ltd., Thiruvananthapuram, India), which has approximately 60 cycles / min of linear oscillation and approximately 36 mm (1.4 inches) of displacement.

[0255] While the device disclosed herein provides enhanced erythrocyte deoxygenation, the use of improved motion provides further removal of oxygen from erythrocytes. It is well known that platelets can be activated by mechanical agitation (such as shear forces) and are therefore limited by how much physical agitation they can tolerate before such activation occurs. Hemolysis of erythrocytes is estimated to occur above approximately 6000 dynes / cm³. 2 The shear stress level required for platelet activation is an order of magnitude higher than that required for platelet activation (Grigioni et al., J. Biomech., 32: 1107-1112 (1999); Sutera et al., Biophys. J., 15: 1-10 (1975)). In some respects, currently available platelet agitators operating at a displacement of about 36 mm and a rate of about 65 cycles per minute (cpm) provide erythrocyte deoxygenation as disclosed herein. In other respects, improved rates and degrees of deoxygenation without hemolysis are achieved using linear oscillatory motion with a displacement between 30 mm and about 125 mm. In the other respects, agitation is a linear oscillation of about 50 mm to about 90 mm.

[0256] This disclosure also provides and includes adjusting the frequency of the oscillation to ensure effective mixing. In addition to a platelet oscillator with a displacement of about 36 mm and a frequency of about 65 cpm, in some aspects, the frequency is about 60 to about 150 cycles per minute (cpm). In some aspects, the agitation frequency is between about 80 cpm and about 120 cpm.

[0257] According to certain aspects of this disclosure, when using an agitator or mixer, various configurations of chambers in the collecting device 10 having more than one chamber are provided. For an agitator moving in a horizontal motion, in one aspect, two to eight horizontal (laid flat on the surface) chambers are arranged as follows: side-by-side, end-to-end, above and below each other, and one or more chambers partially covering the chamber below. In another aspect, for an agitator moving in a vertical motion, two to eight vertical (perpendicular to the surface) chambers are arranged as follows: side-by-side, end-to-end, above and below each other, and one or more chambers partially covering the chamber below. In another aspect, for an agitator moving back and forth up and down at an angle greater than 0 and less than 90 degrees from the horizontal direction, two to eight upright (greater than 0 and less than 90 degrees from the horizontal direction) chambers are arranged as follows: side-by-side, end-to-end, above and below each other, and one or more chambers partially covering the chamber below.

[0258] Another advantage of the agitation and mixing in the oxygen-consuming device 10 is that the movement of blood or blood components caused by the agitator also causes the adsorbent pouches located at the top or bottom of the oxygen-consuming device 10 to move. Because the adsorbent pouches move up and down while at the top, the active components that absorb oxygen in the top space continuously settle. This continuous movement of the active components causes oxidized iron particles to move away from non-oxidized iron particles, thereby accelerating the oxygen absorption potential of the adsorbent.

[0259] This disclosure provides and includes a mixing oxygen consumption device 10 by compressing a collapsible blood container 102. Compression of the collapsible container 102 is achieved by applying pressure at 30 cm / s on one of the larger surfaces of the collapsible container for 1-3 seconds, thereby generating a hydrostatic pressure of 100-300 mmHg within the collapsible container, and then applying pressure at 10-30 cm / s on the opposite surface of the collapsible container for 1-3 seconds, without generating a hydrostatic pressure of 100-300 mmHg within the collapsible container. This operation is performed for 2 to 4 hours.

[0260] This disclosure provides and includes mixing of oxygen-consuming devices 10 by kneading a collapsible blood container 102. Kneading of the collapsible container 102 is achieved by moving a roller-like device along one surface of the collapsible container, thereby completing a full translation within 1-3 seconds, causing the collapsible container to fold and agitate its contents. This operation is performed for 1-2 hours. Alternatively, the roller travels along another surface of the collapsible container, thereby completing a full translation within 1-3 seconds, causing the collapsible container to fold and agitate its contents. This operation is performed for 1-2 hours.

[0261] This disclosure provides and includes a blood storage device 20 for storing oxygen-consuming blood and maintaining the blood in a deoxygenated state during storage. Certain anaerobic blood storage devices (ASBs) are known in the art, including, for example, U.S. Patent No. 6,162,396 to Bitensky et al. Prior art anaerobic blood storage devices do not include ports and inlets designed to be substantially oxygen-impermeable. Therefore, prior art anaerobic storage devices have poor lifespan before use and are susceptible to significant oxygen ingress. As provided in this disclosure, the improved blood storage device 20 includes features designed to maintain the integrity of the device while allowing blood sampling during storage and blood stockpiling. The improved ASB also provides improved oxygen diffusion from the blood, thereby providing additional consumption during storage.

[0262] The blood storage device 20 includes a substantially oxygen-impermeable external receiver 201, a collapsible blood container 202 including positioning features 203 adapted to align the collapsible blood container 202 within the geometry of the external receiver 201; at least one inlet / outlet 30 including a connection to the collapsible blood container 202 and an adhesive 302 to the external receiver 201, wherein the adhesive 302 to the external receiver 201 is substantially oxygen-impermeable, and an oxygen adsorbent 207 located within the external receiver 201.

[0263] As used herein, external receiver 201 is at least equivalent to external receiver 101. Also as used herein, internal collapsible blood container 202 includes the blood container of internal collapsible blood container 102 as described above, and is also provided as a collapsible blood container 202 containing a material with low oxygen permeability (such as PVC). Also as provided herein, oxygen adsorbent 207 is at least equivalent to adsorbent 103 and may be provided in pouch form as discussed above.

[0264] This disclosure also includes and provides blood collection kits. According to one aspect of this disclosure, an oxygen-consuming device for consuming oxygen from the blood is included in the blood collection kit, said oxygen-consuming device reducing or eliminating the introduction of oxygen during the blood collection process. Blood collection kits in the art do not include any features or elements that prevent the introduction of oxygen during the collection process. Thus, kits in the art with multiple containers provide approximately 3cc of residual oxygen / container plus additional intake through materials and fittings, thereby increasing the oxygen saturation (sO2) from approximately 40% to 60% of venous blood oxygen saturation (SvO2) to up to full saturation. According to one aspect of this disclosure, the entire blood collection kit is contained in an oxygen-free or oxygen-reduced environment. In one aspect, the blood collection kit is contained in a substantially oxygen-impermeable kit bag, and the bag includes a quantity of oxygen-absorbing adsorbent. The amount of adsorbent in the blood collection kit according to this disclosure is separate from the amount of adsorbent that may be included in the blood collection bag or anaerobic storage bag, and does not include the amount of adsorbent that may be included in the blood collection bag or anaerobic storage bag.

[0265] According to certain aspects of this disclosure, the amount of oxygen absorber included in the blood collection kit is sufficient to remove oxygen introduced into the blood collection kit during manufacturing. In one aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 10 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 60 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 100 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 200 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 500 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb 10 cc to 500 cc of oxygen. In another aspect, the blood collection kit includes an oxygen absorber sufficient to absorb up to 24,000 cc of oxygen to allow for the lifespan of the management device. According to certain aspects of this disclosure, the oxygen absorber is disposed in one or more pouches.

[0266] On one hand, the amount of oxygen adsorbent is sufficient to maintain an oxygen-consuming environment for the blood collection kit during storage. On the other hand, oxygen is flushed out of the blood collection kit during manufacturing. Therefore, the amount of oxygen adsorbent can be reduced to account for leakage and residual permeability of the essentially impermeable kit packaging.

[0267] This disclosure also includes and provides a substantially oxygen-impermeable additive solution bag. According to one aspect of this disclosure, the substantially oxygen-impermeable additive solution bag prevents the reintroduction of oxygen into the oxygen-depleted blood after oxygen depletion in the oxygen-depleted blood collection bag.

[0268] In some aspects of this disclosure, the method may further include adding an additive solution to the compressed RBC to form a suspension. In some aspects, the additive solution may be selected from the group consisting of: AS-1, AS-3, alone or in combination. AS-5, SAGM, PAGG-SM, PAGG-GM, MAP, SOLX, ESOL, EAS61, OFAS1, and OFAS3. Additive AS-1 is disclosed in Heaton et al., “Use of Adsol preservation solution for prolonged storage of low viscosity AS-1-red blood cells,” Br J Haematol., 57(3): 467-78 (1984). In another aspect, the pH of the additive solution may be from 5.0 to 9.0. In another aspect, the additive may include an antioxidant. In some aspects of this disclosure, the antioxidant may be quercetin, α-tocopherol, ascorbic acid, or an enzyme inhibitor of an oxidase.

[0269] Example:

[0270] Example 1: Manufacturing of External Receiver 101

[0271] The barrier bag is made by using a pair of RollPrints, each approximately 23 x 30.5 cm (9 x 12 inches). Z-film #37-1275 (Rollprint Packaging Products, Inc., Addison, IL) sheets are manufactured by heat-sealing along one edge in a heat-sealing machine along a shorter 23cm length. A multi-layer tube (Pexco, Inc., Athol, MA, or Extrusion Alternatives, Inc., Portsmouth, NH) with a polyethylene outer layer, PVC inner layer, and EVA intermediate adhesive layer (approximately 0.4cm inner diameter × 0.55cm outer diameter × approximately 2.6cm length) is placed on a solid brass mandrel approximately 0.4cm diameter × approximately 2.5cm length and then placed between the films and positioned in the transverse groove of a heat-sealing mold heated to approximately 130°C. The press is activated and 21x10 4 A Pascal (Pa) setting is applied for approximately 4 seconds to create a continuous weld seal along the length of the mold, in which short sections of multi-layered tubing are sealed in place. The short, multi-layered tubing provides an oxygen-impermeable seal around the outer diameter of the tubing while also providing fluid connectivity through the seal. A PVC tubing section (Pexco, Inc., Athol, MA, or Extrusion Alternatives, Inc., Portsmouth, NH) measuring 0.3 cm inner diameter x 0.41 cm outer diameter x approximately 30.5 cm in length is solvent-bonded to the multi-layered tubing on the outside of the bag using cyclohexanone.

[0272] A pulse heat sealer (McMaster Carr #2054T35, McMaster Carr, Inc., Robbinsville, NJ) was used to seal the two long edges of the barrier film, leaving the last remaining short edge of the barrier bag unsealed to place the blood container 102 inside.

[0273] Example 2: Preparation of siloxane sheets

[0274] Liquid silicone rubber (LSR)

[0275] A 25 μm thick siloxane sheet is manufactured by mixing equal parts of a siloxane elastomer dispersion in a suitable solvent (such as xylene, e.g., NuSil MED10-6640). MED 10-6640 is supplied as a two-part resin system. As a first step, parts A and B are mixed equally to produce a dispersion. Air is then removed under vacuum. The vacuum time is selected to ensure no air bubbles remain in the dispersion. The dispersion is then spread under a precise blade and transferred to a custom-made doctor blade coating disc. The sheet is partially cured by heating, and then a sheet of polyester mesh fabric (SurgicalMesh, Inc., Brookfield, CT#PETKM3002) is placed onto the partially cured siloxane sheet. The polyester mesh fabric is pressed into the partially cured sheet by applying a load to the laminate. The laminate was cured using a tilt-curing method with the following combination of times and temperatures: 30 minutes at ambient temperature and humidity, 45 minutes at 75°C (167°F), and 135 minutes at 150°C (302°F), to produce a siloxane film 113 approximately 25 μm thick with integrated spacers 110, the thickness of which does not include the resulting siloxane film. A polyester mesh-like fabric was attached to the cured siloxane film 113 but was not completely encapsulated by the siloxane film 113. One surface of the film 113 had a matte finish suitable for contact with blood or blood products.

[0276] Additional integrated siloxane membranes with thicknesses of approximately 13 μm and 50 μm were manufactured using the siloxane dispersion method.

[0277] Example 3: Manufacturing of the internally collapsible blood container 102

[0278] The siloxane blood bag is manufactured from a pair of siloxane sheets by bonding their edges together with Smooth-On Sil-Poxy RTV adhesive (Smooth-On, Inc., Easton, PA) and placing the bonded sheets between a pair of flat aluminum plates to create the siloxane blood bag. A siloxane inlet tube (McMaster Carr #5236K83, McMaster Carr, Inc., Robbinsville, NJ) is bonded within the seam to provide a fluid passage and nested within a groove in the aluminum plates. The plates are then clamped together with a large bonding clamp, allowing the adhesive to cure overnight. The next day, the siloxane blood bag is removed from the aluminum plates and a leak test is performed by blowing compressed air into it and immersing it in water to observe for bubbles before use. The siloxane blood bag is then placed in an external barrier bag manufactured as described in Example 1.

[0279] The siloxane blood bag was placed inside the barrier bag as disclosed in Example 1, and the siloxane inlet tube of the siloxane blood bag was connected to the multilayer tube using plastic barbed fittings (McMaster Carr #5116K18, McMaster Carr, Inc., Robbinsville, NJ), and an oxygen sensor piece (Mocon #050-979, Mocon, Inc., Minneapolis, MN) was secured inside the barrier bag. A pair of plastic mesh spacers (McMaster Carr #9314T29, NJ McMaster Carr, Inc., Robbinsville, NJ) were cut to approximately 12.7 x 17.8 cm (5 x 7 inches), and one or more oxygen adsorbent pouches (Mitsubishi Gas Chemical America, New York, NY) were secured near the center of each plastic mesh. After only a few seconds, the plastic mesh spacers were placed between the blood bag and the barrier bag, and the last edge of the barrier bag was sealed with a pulse sealing machine. The resulting oxygen consumption device 10 was used for subsequent testing.

[0280] Example 4: Blood Preparation

[0281] Whole blood and blood products, including leukopenic whole blood and leukopenic compressed red blood cells, are prepared using techniques known in the art. The sample is analyzed using a Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA) as instructed according to the manufacturer's instructions, including pH, blood gases, electrolytes, metabolites, quantitative blood oxygenation, and baseline SO2 and PO2 levels. The analysis is performed using the Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA) according to the manufacturer's instructions. The Plasma Low Hb spectrophotometer was used to measure free hemoglobin.

[0282] Blood SO2 levels are increased to typical levels (65% to 90%) for collected whole blood by passing blood or blood components through a Sorin D100 oxygenator (Arvada, CO) that uses oxygen as the exchange gas. All experiments begin with ≥50% SO2 before transferring blood to the oxygen-consuming device for testing.

[0283] Example 5: Deoxygenation Test

[0284] The oxygen consumption device of Example 2 was equipped with blood and tested as follows. Whole blood (124 g) was obtained and saturated with oxygen by injecting a few cc of pure oxygen. The whole blood was then placed in the siloxane blood bag of Example 2 using a Terumo aseptic connection device (SCD) with a weighing bag during the transfer. The oxygen level in the top space of the external receiver 101 was measured using a Mocon OpTech Platinum oxygen analyzer and was determined to be 1.60 Torr at the start of the experiment. An initial blood sample was taken and measured on a Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA), and the saturated oxygen content (sO2) was considered to be 98.7%. The barrier bag containing the blood was placed on a workbench at room temperature (21.0°C) and allowed to stand for 1 hour without stirring. After 1 hour, the sO2 was measured to be 93.5% sO2, and the oxygen in the top space of the barrier bag was measured to be 0.70 Torr oxygen. The blood-containing barrier bag was incubated at room temperature (21.0°C) for approximately 14 hours without agitation. After 14 hours of incubation, SO2 was measured to be 66.7%, while after further incubation at 21°C without agitation for another 7 hours, the final SO2 value was 51.2%. The deoxygenation rate followed first-order kinetics, and the rate constant was calculated to be approximately [value missing] minutes. -1 On the order of magnitude.

[0285] Example 6: Serpentine Carbamate Flow Oxygen Consumption Device

[0286] The collapsible blood bag reported a water vapor transfer rate of 1800 g / m³. 2 A 24-hour breathable polyurethane membrane (American Polyfilm, Branford, CT) is used to fabricate the serpentine flow path by welding a pair of membranes together to create the geometry using a custom heat-sealing mold. The collapsible bag with the serpentine path comprises a series of 12 channels approximately 5 mm wide and 220 mm long, providing a total flow path of approximately 2640 mm. The collapsible bag is sealed within an external barrier layer according to Embodiment 1. As previously described in this disclosure, the resulting consumable device also includes two multilayer tubes sealed at one end, such that the inlet and outlet of the serpentine path are in fluid communication with the multilayer tube segment.

[0287] Two plastic spacer mesh pieces (McMaster Carr #9314T29, McMaster Carr, Inc., Robbinsville, NJ) were cut to approximately 125 x 180 mm (5 x 7 inches) and placed on either side of the collapsible blood container inside the external barrier receiver. Small bags of oxygen adsorbent (SS-200, Mitsubishi Gas Chemical America, NY) were placed between each plastic mesh spacer and between the external barrier container (two bags in total) and the oxygen sensor piece (Mocon #050-979, Mocon, Inc., Minneapolis, MN), and then the final edge of the external barrier receiver was sealed. Standard IV tubing (Qosina T4306, Qosina, Corp., Edgewood, NY) of 914 mm (36 inches) length was solvent-bonded to each multilayer tube using cyclohexanone. Place the ratchet clamp (Qosina#140072, Qosina, Corp., Edgewood, NY) onto the outlet fitting to control the flow.

[0288] A standard 500 mL blood bag (model KS-500, KS Mfg., Avon, MA) was connected to an outlet fitting of the stated length using a Terumo aseptic fitting welder (model TSCD-II, Terumo BCT, Inc., Lakewood, CO). 325 g of blood was filled into a second standard 500 mL blood bag (model KS-500, KS Mfg., Avon, MA) at 20.8°C, and the sample was measured on a Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA) and considered to have 83.0% SO2 and 70.1 mmHg pO2. A ratchet clamp (Qosina #140072, Qosina, Corp., Edgewood, NY) was placed on the outlet fitting to control flow, and then the filled blood bag was connected to the inlet tube using a Terumo aseptic fitting welder (model TSCD-II, Terumo BCT, Inc., Lakewood, CO). The ratchet clamp was closed to prevent flow, and the filled blood bag was suspended from the IV bar so that the inlet fitting was fully extended and the collapsible blood bag was positioned on the lab bench. The outlet bag was weighed on a balance and then placed on the floor with the outlet fitting fully extended. The oxygen level in the headspace of the external receiver was measured using a Mocon Op-Techplatinum oxygen analyzer and was initially assumed to be 0.05 Torr. The clamp was opened and a stopwatch timer was started to measure the flow duration, and after 3 minutes and 25 seconds, the inlet blood bag was emptied and the ratchet clamp was closed. A blood sample was extracted and measured and was assumed to have 84.1% SO2 and 71.6 mmHg PO2, with the increase likely from residual oxygen in the empty loop. The headspace measured 0.00 tortoxygen, and the exit blood bag contained 277 grams of blood.

[0289] An empty inlet blood bag was removed from the IV bar and placed on the floor, while an outlet blood bag containing 277 grams of blood was suspended from the IV bar to repeat the flow. The IV bar was lowered to 457 mm (18 inches) to reduce the flow rate, and the clamps were opened to repeat the cycle. The process was repeated five times, and then a collapsible blood bag was filled with blood and allowed to stand still on the test bench for 80 minutes, during which a terminal blood sample was taken and measured on a hematology analyzer. The results are summarized in the table below, which shows a slight, gradual increase in blood oxygen levels during flow and a slight decrease after standing. The results indicate that the system does not provide significant blood deoxygenation during the study, but rather absorbs oxygen from a permeable standard PVC blood bag. This demonstrates the importance of taking additional measures to prevent oxygen from entering through the inlet, outlet, port, and fittings.

[0290] Table 3: Deoxygenation using urethane bags

[0291]

[0292]

[0293] * 914mm top height; all other flow paths are at a height of 457mm.

[0294] Example 7: Testing of the internal collapsible blood container 102 configuration

[0295] A series of internally collapsible blood containers 102 were prepared according to Table 4 below and sealed within an external receiver 101 as provided in Example 1. Leukopenic compressed red blood cells (LRpRBCs) were introduced into the containers 102. The resulting oxygen consumption device 10 also included a Mocon Optech-O2 sensor. The blood containers assembled according to Table 4 were placed on a Helmer Labs platelet oscillator (model PF96), and blood and headspace samples were acquired and analyzed at time points between 0 and 300 minutes.

[0296] Table 4: Test configuration of internally collapsible blood container 102

[0297]

[0298]

[0299] like Figure 5 As shown, oxygen consumption follows first-order kinetics. Rate constants are provided in Table 5.

[0300] Table 5: Rate Constants

[0301] sample <![CDATA[Rate constant (minutes -1 ) <!-- 41 -->]]> simulation <![CDATA[-1.20x10 -2 ]]> 1A <![CDATA[-1.00x10 -2 ]]> 2A <![CDATA[-0.41x10 -2 ]]> 3A <![CDATA[-0.62x10 -2 ]]> 4A <![CDATA[-0.82x10 -2 ]]> 5A <![CDATA[-0.93x10 -2 ]]> 1B <![CDATA[-1.12x10 -2 ]]> 2B n / a 3B <![CDATA[-1.40x10 -2 ]]> 4B <![CDATA[-1.03x10 -2 ]]> 5B <![CDATA[-1.34x10 -2 ]]> 6B <![CDATA[-0.95x10 -2 ]]>

[0302] Example 8: 30.5 x 30.5 cm (12 x 12 inches) thick siloxane bag

[0303] The collapsible blood container 102 is manufactured by bonding a pair of silicone sheets (McMaster Carr #87315K71, McMaster Carr, Inc., Robbinsville, NJ) with a periphery of Sil-Poxy silicone adhesive (Smooth-On, Inc., Easton, PA), with a thickness of 152 μm and 228 μm respectively, and bonding a silicone tubing (McMaster Carr #9628T42, McMaster Carr, Inc., Robbinsville, NJ) as an inlet tube for fluid communication. The bonded sheets are cured for two days between clamped aluminum plates.

[0304] The collapsible blood bag inlet tube was connected to the multi-layered tube of the external receiver barrier bag 101 according to Example 1 using a plastic barbed fitting (McMaster Carr #5116K18, McMaster Carr, Inc., Robbinsville, NJ). The resulting external receiver bag 101 was subjected to a leak test by blow-in immersion as described in Example 1.

[0305] Device 10 is assembled with two 330x330mm mesh spacers (McMaster Carr #9314T29, McMaster Carr, Inc., Robbinsville, NJ) and four oxygen adsorbent pouches (SS-200, Mitsubishi Gas Chemical America, NY, NY) are tapered to each mesh spacer, collapsible blood container, and oxygen sensor chip (Mocon #050-979, Mocon, Inc., Minneapolis, MN) inserted into and heat-sealed within barrier bag 101. An inlet tube containing a standard IV fitting (200mm Qosina T4306, Qosina, Corp., Edgewood, NY) is bonded to the multilayer tube of barrier bag 101 using cyclohexanone solvent. A ratchet clamp (Qosina #140072, Qosina, Corp., Edgewood, NY) provides flow control.

[0306] A pair of matched blood units for the study was prepared by adjusting the hematocrit to 50% after centrifugation and recombining red blood cells and the required amount of plasma to achieve the target hematocrit. Initial blood SO2 was measured on a Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA) and considered to have 39.0% SO2; prior to the start of the study, three injectable solutions containing 30 cc of 100% oxygen were added to the blood to obtain an SO2 level of 85.6%. A portion of the blood was transferred to a standard 500 mL blood bag (model KS-500, KS Mfg., Avon, MA) weighed by tare weight and filled with 532 grams of blood to represent a typical 500 mL blood unit with high hematocrit and saturated oxygen levels. Using a Terumo aseptic fitting welder (model TSCD-II, Terumo BCT, Inc., Lakewood, CO), a standard 500mL blood bag (model KS-500, KS Mfg., Avon, MA) was connected to an inlet fitting of the stated length, and the contents were transferred to the collapsible blood bag to be tested.

[0307] Collapsible blood bags were placed on a Helmer PF96 platelet agitator (Helmer Scientific, Nobelsville, IN), and blood samples were taken and measured on a Radiometer ABL-90 blood analyzer (Radiometer America, Brea, CA), while headspace oxygen levels were measured on a Mocon Op-Tech platinum oxygen analyzer (Mocon, Inc., Minneapolis, MN). Initially, the blood was assumed to have 84.5% SO2 and a headspace oxygen partial pressure of 2.48 Torr. Samples were agitated on the platelet agitator, and samples were taken and measured every 30 minutes for 150 minutes. The results are summarized in Table 6 below.

[0308] Table 6: Usage 30.5x30.5cm Deoxygenation of silicone bags

[0309] Time (minutes) <![CDATA[sO2%]]> <![CDATA[pO2mmHg]]> <![CDATA[pCO2 mmHg]]> <![CDATA[Top Space O2 Support]]> 0 84.5 63.9 88.9 2.48 30 70.3 40.0 50.7 4.63 60 64.9 34.9 43.6 5.24

[0310] The calculated deoxygenation rate constant is -0.34 x 10⁻⁶. -2 minute -1 .

[0311] Example 9: Effect of mixing on oxygen consumption

[0312] Four oxygen-reducing bags (ORBs) with siloxane-filled collapsible blood containers 102 were prepared according to Example 3. The collapsible blood containers 102 were filled with leukopenic compressed red blood cells (LRPRBCs) prepared according to Example 4 to obtain approximately 6 cm³ of [material / material]. 2 / ml surface area to volume (SAV) ratio. Three LRPRBC-filled ORBs were placed flat on a Helmer PF-96 platelet agitator (Noblesville, IN) or PF-8 agitator, with standard cycles per minute (72 cpm) or modified to linear oscillations at reduced standard cpm (42 cpm). A third set of filled ORBs was placed on a Benchmark 3D 5RVH6 agitator (Sayretville, NJ). Samples were collected at 0, 60, 120, and 180 minutes, and the various ABL-90 outputs listed in Example 4 were analyzed.

[0313] like Figure 12 As shown, compared with the mixing method of linear oscillation, 3D mixing leads to the highest oxygen consumption rate and T0. 180 The lowest SO2 percentage was achieved. Furthermore, the standard CPM linear oscillation (SLO) yielded a higher oxygen consumption rate compared to the linear oscillation of reduced standard CPM (R-SLO).

[0314] Example 10: Effect of surface area to volume ratio on oxygen consumption

[0315] In another example, six oxygen reduction bags (ORBs) with internal collapsible blood containers 102 were prepared using Bentec siloxane. LRPRBCs were collected and prepared according to Example 4. The siloxane-filled collapsible blood containers 102 were filled with 176, 220, 250, 270, 300, and 350 mL of LRPRBCs to provide 3.41–6.8 cm⁻¹ as shown in Table 7. 2 The surface to area ratio between / ml. As described in Example 4, the SO2 percentage was measured in ORB containing various LRPRBC volumes at 0, 30, 60, 120, and 180 minutes.

[0316] Table 7: Surface Area to Volume Ratio

[0317] Blood volume (ml) 176 220 250 270 300 350 <![CDATA[SAV ratio (cm 2 / ml)]]> 6.8 5.45 4.8 4.4 4 3.41

[0318] like Figure 13 As shown, once the SAV ratio is below 5.45cm 2 / ml, the surface area kinetic rate decreases.

[0319] In another example, five oxygen reduction bags (ORBs) with internal collapsible blood containers 102 were prepared using PVDF instead of siloxane. LRPRBCs were collected and prepared according to Example 4. The PVDF internal collapsible blood containers 102 were filled with blood volumes of 95, 110, 220, 300, or 360 ml to provide surface area to volume ratios as shown in Table 8. As described in Example 4, the SO2 percentage in ORBs containing various LRPRBC volumes was measured at 0, 30, 60, 120, and 180 minutes.

[0320] like Figure 14 As shown, when the SAV ratio is greater than 5, the lowest SO2 percentage is reached after 180 minutes.

[0321] Table 8: Surface Area to Volume Ratio

[0322] Blood volume (ml) 95 110 220 300 360 <![CDATA[SAV ratio (cm 2 / ml)]]> 6.8 5.9 2.9 2.2 1.8 Dynamic rate (x100) -1.39 -1.9 -0.82 -0.06 -0.32

[0323] In another example, four oxygen-reducing bags (ORBs) with single- or double-sided membranes (PSU or PVDF) were prepared. LRPRBCs were collected and prepared according to Example 4. An inner collapsible blood container 102 was filled with 112-118 ml of LRPRBCs to provide a 50% reduction in surface area volume in the double-sided membrane. The SO2 percentage was measured in the ORBs containing single- or double-sided membranes as described in Example 4. Figure 15 As shown, a 50% reduction in surface area results in a 50-60% reduction in total kinetic velocity.

[0324] Example 11: Fabrication of a foldable blood container from microporous polysulfone or PVDF

[0325] A heat-sealed, oxygen-permeable, collapsible blood container 102 of polysulfone and PVDF was prepared. The prepared seal resulted in disruption of the membrane's microporous structure, creating crystalline regions sensitive to bending stresses associated with fluid movement within the resulting container 102. The container 102 was susceptible to leakage and damage and was unsuitable for use with ORB intended outside of experimental environments.

[0326] To overcome the inability to heat-seal polysulfone or PVDF membranes in a manner suitable for transfusion medicine, a heat-laminated "bonding" layer 105 is included in the construction of a container 102 made of a porous membrane 113. Figure 9B As shown, the sealing area is enhanced by pre-laminating strips of low-density polyethylene (LDPE) onto the inner surfaces of the upper and lower films to align with the bag sealing area. Figure 9B As shown, pre-lamination results in pre-lamination of seal 107. (As indicated...) Figure 9B As shown, the two pre-laminated membranes 113 (114) are then heat-sealed to form a seal 108. Also as... Figure 9B As shown, the bonding layer extends beyond the width of the seal by a certain amount.

[0327] LDPE melts at approximately 105°C, significantly lower than the melting temperatures of polysulfone (187°C) or PVDF (177°C). The bag is formed by aligning the sealing areas and heat-sealing the upper and lower films together. Without being limited to a specific mechanism, it is believed that LDPE flows into the membrane pores, serving as a reinforcing strain relief device inside the seal and a low-temperature "bonding" layer for the seal.

[0328] In addition to enhancing the seal between the microporous membranes 113, the bonding layer also serves as a geometric feature 121. Therefore, the entire internal geometry can be easily adjusted by selecting the shape of the bonding layer 105. An example of an exemplary geometry is shown in Figure 10. As shown, the geometric feature 121 provides a circular internal geometry, thereby avoiding mixing reduction associated with corners. As shown in Figure 10, the resulting container 102 can be elliptical or circular and may also include a mixing feature 119, which provides circulatory flow of blood products and enhances mixing.

[0329] The internally collapsible blood bag is manufactured from a pair of Millipore PVDF membranes with 0.22 μm pore size and 177 x 177 mm square dimensions by first thermally bonding a low-density polyethylene (LDPE) bonding layer frame to each membrane. The LDPE bonding layer frame is approximately 0.02–0.10 mm thick and has external dimensions of approximately 177 x 177 mm square and internal dimensions of approximately 160 x 160 mm square, used in conjunction with a 15 mm wide seal to provide approximately 4 mm overlap between the seal edge and the end of the bonding layer, thus providing stress relief at the seal edge. The bonding layer frame is thermally bonded to the PVDF membrane using a pulse heat sealer. As previously described, the membranes with the bonding layers bonded are then thermally sealed together around their peripheries using a pair of custom-made constant-heat aluminum molds with tubular sealing grooves to produce the internally collapsible blood container. A pair of Conwed Thermanet Part #R03470 polymer-integrated mesh sheets are cut to approximately 10 mm beyond the perimeter of the inner foldable blood bag and placed on both sides of the inner foldable blood bag, with the adhesive side of the polymer-integrated mesh in contact with the inner foldable blood bag. The assembly is placed between a pair of aluminum plates and heated to approximately 93-110°C, up to 120°C, for approximately 3-15 minutes to melt the adhesive and allow it to flow into the pores of a PVDF membrane, which is located directly beneath the integrated polymer mesh and also surrounds the perimeter of the inner foldable blood bag in contact with the polymer-integrated mesh, thereby providing a strong mechanical bond. The assembly is cooled to below approximately 50°C, and then the plates are removed.

[0330] Example 12: Effect of spacer 110 on deoxygenation rate

[0331] The internal foldable blood bag and oxygen consumption device are based on the above embodiments with and without the spacer 110 according to this disclosure. Figure 16 As shown, the incorporation of spacer 110 significantly increases the oxygen consumption rate.

[0332] Although the invention has been described with reference to specific embodiments, those skilled in the art will understand that various changes can be made and equivalents can be used to replace its elements without departing from the scope of the invention. Furthermore, many modifications can be made to adapt specific circumstances or materials to the doctrine of the invention without departing from the scope of the invention.

[0333] Therefore, it is intended that the present invention be limited to the specific embodiments disclosed as the best mode for carrying out the invention, but rather that the invention include all embodiments within the scope and spirit of the appended claims.

[0334] This invention also relates to the following embodiments (which correspond to the claims of the original application):

[0335] 1. An oxygen consumption device 10 for consuming oxygen from blood prior to anaerobic storage, comprising: an external receiver 101' which is substantially impermeable to oxygen;

[0336] An internal collapsible blood container 102 includes one or more oxygen-permeable chambers; and an oxygen adsorbent 103 located within the external receiver 101.

[0337] 2. The oxygen consumption device 10 as described in embodiment 1, wherein the oxygenated blood collected in the oxygen consumption device 10 is at least -1.28 x 10⁻⁶. -2 minute -1 The rate is consumed.

[0338] 3. The oxygen consumption device 10 as described in embodiment 1, wherein the internal blood compatibility bag 102, when filled with blood for consumption and sealed within the external receiver 101, has a diameter of at least 4.48 cm. 2 / ml (cm) 2 The ratio of surface area to volume ( / ml).

[0339] 4. The oxygen consumption device 10 as described in embodiment 1, wherein the blood compatibility bag 102 comprises a material with an oxygen permeability of at least about 25 bar.

[0340] 5. The oxygen consumption device as described in embodiment 1, wherein the oxygen consumption device 10 further includes a top space defined by the blood compatibility bag 102 and the substantially oxygen-impermeable external receiver 101, wherein the oxygen adsorbent 103 is disposed.

[0341] 6. The oxygen consumption device as described in embodiment 1, wherein the thickness of the collapsible blood container 102 is selected from the group consisting of: 20 micrometers (μm), 30 μm, 50 μm, 76 μm and 120 μm.

[0342] 7. The oxygen consumption device as described in embodiment 1, wherein the collapsible blood container 102 comprises a polyvinylidene fluoride (PVDF) microporous membrane with a pore size ranging from about 0.05 micrometers (μm) to about 1.5 μm.

[0343] 8. The oxygen consumption device as described in embodiment 1, wherein the collapsible blood container 102 is manufactured by blow molding or insert molding.

[0344] 9. The oxygen consumption device as described in embodiment 1, further comprising an oxygen indicator 206 located between the external receiver 101 and the internal collapsible blood container 102.

[0345] 10. The oxygen consumption device as described in embodiment 1, further comprising a top space with a volume between 10 ml and 1000 ml.

[0346] 11. The oxygen consumption device as described in embodiment 1, further comprising:

[0347] At least one inlet / outlet 30 through the external receiver 101 includes a tube 301 and an adhesive 302, wherein the tube 301 and the adhesive 302 are substantially oxygen-impermeable, and the inlet / outlet 30 is in fluid communication with the collapsible container 102.

[0348] 12. The oxygen consumption device as described in embodiment 11, wherein the inlet / outlet 30 further includes a port 303.

[0349] 13. The oxygen-consuming device as described in embodiment 2, wherein the surface area to volume ratio is at least 4.48 cm². 2 / ml, 5cm 2 / ml or at least 5.5cm 2 / ml.

[0350] 14. The oxygen-consuming device as described in embodiment 1, wherein the internal collapsible blood container 102 is configured such that the blood contained therein forms a layer with a thickness of less than 1 cm.

[0351] 15. The oxygen consumption device of embodiment 1, wherein the internal collapsible blood container 102 comprises silicon with a thickness ranging from about 15 μm to about 200 μm.

[0352] 16. The oxygen-consuming device as described in embodiment 15, wherein the thickness is selected from the group consisting of: 20 μm (μm), 30 μm, 50 μm, 76 μm and 120 μm.

[0353] 17. The oxygen consumption device as described in embodiment 1, wherein the internal collapsible blood container 102 has a cylindrical shape.

[0354] 18. The oxygen consumption device as described in embodiment 1, further comprising a spacer material 110 enclosed in the external receiver 101.

[0355] 19. The oxygen-consuming device as described in embodiment 18, wherein the spacer material 110 is a mesh.

[0356] 20. The oxygen-consuming device as described in embodiment 19, wherein the mesh 110 is selected from the group consisting of: molded mats, woven mats, nonwoven mats, twisted yarns, and twisted mats.

[0357] 21. The oxygen consumption device as described in embodiment 19, wherein the mesh 110 comprises an area greater than 0.75 mm². 2 At least one gap 111.

[0358] 22. The oxygen consumption device as described in embodiment 21, wherein the gap space occupies at least 30% of the area of ​​the mesh 110.

[0359] 23. The oxygen consumption device as described in embodiment 1, wherein the internal collapsible blood container 102 includes one or more baffles.

[0360] 24. The oxygen consumption device as described in embodiment 1, wherein the internal collapsible blood container comprises a hydrophobic material with a contact angle greater than 150° or a hydrophobic material with a contact angle greater than 90°.

[0361] 25. The oxygen-consuming device as described in embodiment 1, wherein the internal collapsible blood container 102 comprises a material with an oxygen permeability of at least about 25 bar.

[0362] 26. The oxygen consumption device of embodiment 1, wherein the internal collapsible blood container 102 comprises a polyvinylidene fluoride (PVDF) microporous membrane with a pore size in the range of about 0.05 μm to about 1.5 μm.

[0363] 27. The oxygen consumption device of embodiment 26, wherein the internal collapsible blood container 102 further includes a transparent window 112 on the surface.

[0364] 28. The oxygen-consuming device as described in embodiment 26, wherein the pore size of the PVDF microporous membrane is selected from the group consisting of: 0.1 μm, 0.22 μm and 1.0 μm.

[0365] 29. The oxygen-consuming device as described in embodiment 1, wherein the total mass of the oxygen adsorbent 103 is at least 1 gram.

[0366] 30. The oxygen-consuming device as described in embodiment 1, wherein the oxygen adsorbent 103 further includes a carbon dioxide adsorbent.

[0367] 31. The oxygen consumption device as described in embodiment 1, wherein the oxygen adsorbent 103 is positioned outside the internal collapsible blood container 102.

[0368] 32. The oxygen consumption device as described in embodiment 1, wherein the oxygen adsorbent 103 is located inside the internal collapsible blood container 102.

[0369] 33. The oxygen consumption device as described in embodiment 1, wherein the internal collapsible blood container 102 includes at least two oxygen-permeable chambers and the chambers are in fluid communication.

[0370] 34. The oxygen-consuming device as described in embodiment 33, wherein the at least two oxygen-permeable chambers are stacked within the external receiver 101.

[0371] 35. The oxygen-consuming device as described in embodiment 33, wherein the at least two oxygen-permeable chambers are arranged side-by-side within the external receiver 101.

[0372] 36. The oxygen consumption device as described in embodiment 33, wherein the internal collapsible blood container 102 includes two to eight oxygen-permeable chambers, and the chambers are in fluid communication.

[0373] 37. The oxygen consumption device as described in embodiment 36, wherein the two to eight chambers are arranged side by side within the external receiver.

[0374] 38. The oxygen consumption device of embodiment 34, wherein the at least one adsorbent 103 is positioned between the stacked chambers of the internal collapsible blood container 102.

[0375] 39. A method for preparing blood for storage, comprising:

[0376] Provides an oxygen consumption device 10, which includes:

[0377] External receiver 101, which is substantially oxygen-impermeable;

[0378] An internal collapsible blood container 102, which is enclosed within the external receiver; and

[0379] Oxygen adsorbent 103, located between the external receiver 101 and the internal blood-compatible blood container 102, allows blood to flow into the internal collapsible blood container 102 of the oxygen consumption device 10.

[0380] It produces blood with less than 20% oxygen saturation.

[0381] 40. The method of embodiment 39, wherein the blood is selected from the group consisting of whole blood, compressed red blood cells (pRBCs), leukopenic compressed red blood cells (LRpRBCs), thrombocytopenic compressed red blood cells, plasma, and platelets.

[0382] 41. The method of embodiment 40, wherein the oxygen saturation of the oxygen-depleted blood is less than 10%.

[0383] 42. The method of embodiment 40, wherein the oxygen saturation of the oxygen-depleted blood is less than 5%.

[0384] 43. The method of embodiment 40, wherein the oxygen saturation of the oxygen-depleted blood is less than 3%.

[0385] 44. The method of embodiment 40, wherein the blood is whole blood, and the internal collapsible blood container 102 further includes an anticoagulant.

[0386] 45. The method as described in embodiment 44, wherein the temperature of the whole blood is about 37°C.

[0387] 46. ​​The method as described in embodiment 44, wherein the temperature of the whole blood is about 25°C.

[0388] 47. The method of embodiment 40, wherein the blood comprises leukopenic compressed red blood cells (LRpRBCs).

[0389] 48. The method of embodiment 47, wherein the temperature of the leukopenic compressed red blood cells (LRpRBCs) is approximately 25°C.

[0390] 49. The method of embodiment 44, further comprising removing platelets, plasma and leukocytes from the oxygen-depleted whole blood to prepare leukopenic compressed red blood cells.

[0391] 50. The method of embodiment 40, further comprising transferring the oxygen-depleted blood having an oxygen saturation of less than 20% to the blood storage device 20.

[0392] 51. The method of embodiment 39, further comprising agitating the blood in the internal collapsible blood container 102 for a period between 30 minutes and 24 hours.

[0393] 52. The method of embodiment 39, wherein the agitation is selected from the group consisting of: shaking, nutation, rotation, stirring, kneading, oscillation, linear oscillation and compression of the oxygen-consuming device.

[0394] 53. The method of embodiment 40, wherein the method is performed at ambient temperature or about 25°C.

[0395] 54. The method of embodiment 39, further comprising purging the external receiver of the device with nitrogen and removing the nitrogen from the device prior to the flow.

[0396] 55. The method as described in embodiment 39, wherein the initial oxygen saturation of the whole blood prior to the whole blood is at least 55%.

[0397] 56. The method of embodiment 55, wherein the oxygen-depleted blood having an oxygen saturation of less than 20% is produced within 12 hours after collection from the donor.

[0398] 57. The method of embodiment 55, wherein the oxygen-depleted blood having an oxygen saturation of less than 20% is produced within 8 hours after collection from the donor.

[0399] 58. The method of embodiment 55, wherein the oxygen-depleted blood having an oxygen saturation of less than 20% is produced within 6 hours after collection from the donor.

[0400] 59. The method of embodiment 55, wherein the oxygen-depleted blood having an oxygen saturation of less than 20% is produced within 4 hours after collection from the donor.

[0401] 60. A blood storage device 20 for storing oxygen-consuming blood, comprising:

[0402] External receiver 201, which is substantially oxygen-impermeable;

[0403] Collapsible blood container 202, which includes

[0404] Positioning feature 203, which is adapted to be aligned with the collapsible blood container within the geometry of the external receiver 201;

[0405] At least one inlet / outlet 30, comprising a tube 106 connected to the collapsible blood container 202 and an adhesive 302 to the external receiver 201, wherein the adhesive 302 to the external receiver 201 is substantially oxygen-impermeable; and

[0406] Oxygen adsorbent 103 is located within the external receiver 201.

[0407] 61. The blood storage device as described in embodiment 60, wherein the tubing 106 is a multilayered tubing that is substantially oxygen-impermeable.

[0408] 62. The blood storage device as described in embodiment 61, wherein the inlet / outlet 30 includes a tube 301 connected to a substantially oxygen-impermeable fitting 205.

[0409] 63. The blood storage device as described in embodiment 61, wherein the inlet / outlet 30 includes a pipe 301 connected to a fitting 106 comprising polyvinyl chloride (PVC).

[0410] 64. The blood storage device of embodiment 61, wherein the external receiver 201 and the tubing 205 are substantially oxygen-impermeable, and the blood in the collapsible blood container maintains an oxygen partial pressure (PO2) of less than 15 mmHg during a storage period of up to 64 days.

[0411] 65. The blood storage device as described in embodiment 60, wherein the oxygen adsorbent has a capacity of at least 60 cubic centimeters (cc) of oxygen.

[0412] 66. The blood storage device as described in embodiment 60, wherein the substantially oxygen-impermeable adhesive 302 is solvent-sealed, heat-sealed, adhesively bonded, ultrasonically welded, or radio frequency welded.

[0413] 67. The blood storage device of embodiment 60, wherein the positioning feature 203 is selected from the group consisting of: geometric cuts, tactile surface marks, die-cut reference points, spacers, interlocking cuts, and printed marks.

[0414] 68. The blood storage device of embodiment 60, wherein the collapsible blood container 202 is manufactured by blow molding or insert molding.

[0415] 69. The blood storage device of embodiment 60, wherein the collapsible blood container 202 further includes one or more inlets / outlets 30, which include a tube 301 and an adhesive 302, wherein the tube 301 and the adhesive 302 are substantially oxygen-impermeable.

[0416] 70. The blood storage device as described in embodiment 69, wherein the collapsible blood container 202 further includes two inlets / outlets 30.

[0417] 71. The blood storage device as described in embodiment 70, wherein the collapsible blood container further includes a third inlet / outlet 30.

[0418] 72. A method for reducing oxygen from whole blood or its components, the method comprising:

[0419] The whole blood or its components are placed in device 20 for a certain period of time, the device including an external receiver 201 that is substantially oxygen-impermeable.

[0420] Collapsible blood container 202, which is highly permeable to oxygen and includes

[0421] Positioning feature 203, which is adapted to be aligned with the collapsible blood container 201 within the geometry of the external receiver 201;

[0422] At least one inlet / outlet 30, comprising a tube 301 and an adhesive 302 and connected to the inner bag 202, wherein the adhesive 302 is substantially oxygen-impermeable to the outer receiver 201; and

[0423] Oxygen adsorbent 207, located within the external receiver 201 and outside the internal blood bag 202; and

[0424] The device 20 containing the whole blood or its components is incubated for a certain period of time.

[0425] 73. The method of embodiment 72, further comprising agitating the whole blood or a component thereof stored in the device.

[0426] 74. The method of embodiment 72, wherein the incubation is performed at ambient temperature.

[0427] 75. The method of embodiment 72, wherein the incubation is at 4°C to 6°C.

[0428] 76. The method of embodiment 72, wherein the incubation lasts for a period of up to 64 days.

[0429] 77. The method of embodiment 72, wherein the whole blood or a component thereof is whole blood.

[0430] 78. The method of embodiment 72, wherein the components are selected from the group consisting of: compressed red blood cells, leukopenic compressed red blood cells, platelets, and plasma.

[0431] 79. The method of embodiment 78, wherein the component thereof is compressed red blood cells.

[0432] 80. The method of embodiment 72, wherein the time period is selected from the group consisting of: up to 15 minutes, up to 30 minutes, between 2 and 3 hours, between 2 and 4 hours, up to 6 hours, up to 8 hours, and up to 24 hours.

[0433] 81. The method of embodiment 73, wherein the agitation provides a lateral agitation of at least 3 cm in a translational manner and at a rate of at least once per second.

[0434] 82. The method of embodiment 73, wherein the agitation provides tumbling at a rate of at least once every 5 seconds.

[0435] 83. The method of embodiment 82, wherein the flipping is a partial flipping of the device.

[0436] 84. The method of embodiment 82, wherein the flipping is a complete flipping of the device.

[0437] 85. The method of embodiment 73, wherein the agitation comprises pushing or compressing one or more locations on the collapsible blood container at a rate of at least five times per second.

[0438] 86. The method of embodiment 73, wherein the agitation is selected from the group consisting of: shaking, nutation, rotation, stirring, kneading, oscillation and compression of the collapsible blood container.

[0439] 87. The method of embodiment 72, wherein the absorption rate of the oxygen adsorbent 207 is at least 10 cubic centimeters / gram adsorbent / hour (cc·g). -1 ·Hour -1 ).

[0440] 88. The method of embodiment 87, wherein the absorption rate of the oxygen adsorbent 207 is at least 5 cubic centimeters / gram adsorbent / hour (cc·g). -1 ·Hour -1 ).

[0441] 89. The method of embodiment 72, wherein the external receiver further includes a gas port, and the method further includes removing gas from the top space between the external receiver and the internal blood bag by means of a vacuum.

[0442] 90. An oxygen-consuming device 10 for consuming oxygen from blood prior to anaerobic storage, comprising: an external receiver 101 that is substantially impermeable to oxygen;

[0443] An internal collapsible blood container 102 is made of an integrated siloxane membrane 113 and includes one or more oxygen-permeable chambers;

[0444] Spacer 110; and

[0445] Oxygen adsorbent 103 is located inside the external receiver 101.

[0446] 91. The oxygen-permeable collapsible blood container 102 as described in embodiment 90, wherein the integrated siloxane membrane 113 has a thickness between about 15 μm and about 200 μm.

[0447] 92. The oxygen-permeable collapsible blood container 102 as described in embodiment 91, wherein the integrated siloxane membrane 113 has a thickness of less than or equal to 76 μm.

[0448] 93. The oxygen-permeable collapsible blood container 102 as described in embodiment 91, further comprising at least one bonding layer 105.

[0449] 94. The oxygen-permeable collapsible blood container 102 as described in embodiment 93, wherein the collapsible blood container 102 includes two bonding layers 105.

[0450] 95. The oxygen-permeable collapsible blood container 102 as described in embodiment 93, wherein the bonding layer 105 comprises siloxane.

[0451] 96. The oxygen-permeable collapsible blood container 102 as described in embodiment 95, wherein the bonding layer 105 comprises liquid siloxane rubber (LSR).

[0452] 97. An oxygen-permeable collapsible blood container 102 as described in embodiment 90, wherein the inner blood compatibility bag 102 has a diameter of at least 4.85 cm when filled with blood for consumption and sealed within the outer receiver 101. 2 / ml (cm) 2 The ratio of surface area to volume ( / ml).

[0453] 98. An oxygen-consuming device 10 for consuming oxygen from blood prior to anaerobic storage, comprising: an external receiver 101 that is substantially impermeable to oxygen;

[0454] An internal collapsible blood container 102 is made of a microporous membrane 113 and includes one or more oxygen-permeable chambers;

[0455] Spacer 111; and

[0456] Oxygen adsorbent 103 is located inside the external receiver 101.

[0457] 99. An oxygen-permeable collapsible blood container 102 comprising first and second microporous membranes 113 connected by a peripheral bonding layer 105, the bonding layer 105 comprising a material having a melting temperature at least 3°C ​​lower than the melting temperature of the microporous membranes 113.

[0458] 100. An oxygen-permeable collapsible blood container 102 as described in embodiment 100, wherein the melting temperature of the bonding layer 105 is at least 10°C lower than the melting temperature of the microporous membrane 113.

[0459] 101. The oxygen-permeable collapsible blood container 102 as described in embodiment 98, wherein the microporous membrane 113 is composed of a microporous membrane selected from the group consisting of: polysulfone, hydrophobic polyvinylidene fluoride (PVDF), cellulose ester, mixed ester of cellulose (MCE), polyethersulfone (PES), hydrophobic polypropylene, and polyacrylonitrile.

[0460] 102. The oxygen-permeable collapsible blood container 102 as described in embodiment 101, wherein the microporous membrane 113 is made of polysulfone or hydrophobic polyvinylidene fluoride (PVDF).

[0461] 103. The oxygen-permeable collapsible blood container 102 as described in embodiment 98, wherein the peripheral bonding layer 105 is made of low-density polyethylene (LDPE).

[0462] 104. A method for preparing an internally collapsible blood container 102 having an integrated spacer 110, the method comprising:

[0463] A liquid siloxane rubber (LSR) suspension layer of 20 μm to 750 μm is applied to the surface;

[0464] The LSR layer is cured in the first curing step to prepare a partially cured layer;

[0465] Spacers 110, including mesh, are applied to the partially cured layer;

[0466] A second curing step is performed to prepare a cured siloxane film 113 with an integrated spacer 110, ranging from 10 μm to 100 μm in thickness.

[0467] 105. The method of embodiment 104, wherein the LSR is suspended in xylene, hexane, tert-butyl acetate, heptane, acetone or naphtha.

[0468] 106. The method of embodiment 104, wherein the LSR is suspended in xylene.

[0469] 107. The method of embodiment 104, wherein the LSR is a suspension of 10% to 30%.

[0470] 108. The method of embodiment 104, further comprising assembling the siloxane membrane 113 having integrated spacers 110 into the internal collapsible blood container 102.

Claims

1. An oxygen depletion and storage system for consuming and storing oxygen from blood, the system comprising: An oxygen-consuming component (10) for consuming oxygen from the blood, comprising: The first external receiver (101) is substantially oxygen-impermeable; A first internal collapsible blood container (102) includes one or more oxygen-permeable chambers; The first group of at least one inlet / outlet (30), each inlet / outlet of the first group of at least one inlet / outlet (30) includes a fitting (106) connected to the first internal collapsible blood container (102) and a tube (301) and an adhesive (302) connected to the first external receiver (101), wherein the tube (301) and the adhesive (302) connected to the first external receiver (101) are substantially oxygen-impermeable; A first mesh or pad spacer (110) comprising an open space (111), wherein the first mesh or pad spacer (110) is located between the first external receiver (101) and the first internal collapsible blood container (102), the first mesh or pad spacer (110) maintaining a first top space between the first external receiver (101) and the first internal collapsible blood container (102), and wherein 50% to 80% of the total area of ​​the first mesh or pad spacer (110) is an open area; and A first oxygen adsorbent (103) is disposed within the first top space, wherein the first top space ensures effective diffusion of oxygen from the surface of the first internal collapsible blood container (102) to the first oxygen adsorbent (103), and An anaerobic blood storage assembly (20) for storing the oxygen-consuming blood includes... The second external receiver (201) is essentially oxygen-impermeable; The second internal collapsible blood container (202) includes a positioning feature (203) adapted to align the second internal collapsible blood container (202) within the geometry of the second external receiver (201). The second group of at least one inlet / outlet (30), each inlet / outlet of the second group of at least one inlet / outlet (30) includes a fitting (106) connected to the second internal collapsible blood container (202) and a tube (301) and an adhesive (302) connected to the second external receiver (201), wherein the tube (301) and the adhesive (302) connected to the second external receiver (201) are substantially oxygen-impermeable; A second mesh or pad spacer (213) comprising an open space (111) wherein the second mesh or pad spacer (213) is located between the second external receiver (201) and the second internal collapsible blood container (202), the second mesh or pad spacer (213) maintaining a second top space between the second external receiver (201) and the second internal collapsible blood container (202), and wherein 50% to 80% of the total area of ​​the second mesh or pad spacer (213) is an open area; as well as A second oxygen adsorbent (207) is disposed within the second top space, wherein the second top space ensures effective diffusion of oxygen from the surface of the second internal collapsible blood container (202) to the second oxygen adsorbent (207).

2. The oxygen reduction storage system of claim 1, wherein the oxygen reduction storage system further comprises a bleeding needle, a blood collection bag containing an anticoagulant solution, and a fitting sufficient to connect the blood collection bag to the oxygen consumption assembly (10).

3. The oxygen reduction storage system of claim 1, wherein the oxygen consumption component (10) further comprises an anticoagulant solution.

4. The oxygen reduction storage system of claim 1, wherein the oxygen reduction storage system is disposable.

5. The oxygen reduction storage system of claim 1, wherein the oxygen consumption component (10) further includes an oxygen indicator (104) that provides an indication of the amount of oxygen present.

6. The oxygen reduction storage system of claim 1, wherein the anaerobic blood storage component (20) further includes an oxygen indicator (206) wherein the oxygen indicator (206) provides an indication of the amount of oxygen present.

7. The oxygen reduction storage system of claim 1, wherein the fitting (106) is a multilayer fitting that is substantially impermeable to oxygen.

8. The oxygen reduction storage system of claim 1, wherein the positioning feature (203) is selected from the group consisting of: geometric cuts, tactile surface marks, die-cut reference points, spacers, interlocking cuts, and printed marks.

9. The oxygen reduction storage system of claim 1, wherein the first oxygen adsorbent (103) has a binding capacity of at least 100 cubic centimeters (cc) of oxygen at standard temperature and pressure.

10. The oxygen reduction storage system of claim 1, wherein the first oxygen adsorbent (103) further comprises a carbon dioxide adsorbent.

11. The oxygen reduction storage system of claim 1, wherein the second oxygen adsorbent (207) has a binding capacity of at least 60 cubic centimeters (cc) of oxygen at standard temperature and pressure.

12. The oxygen reduction storage system of claim 1, wherein the second oxygen adsorbent (207) further comprises a carbon dioxide adsorbent.

13. The oxygen reduction storage system of claim 1, wherein the first internal collapsible blood container (102) comprises a microporous membrane selected from the group consisting of: polyvinylidene fluoride (PVDF) microporous membrane, polysulfone microporous membrane, polyolefin microporous membrane and polytetrafluoroethylene (PTFE) microporous membrane.

14. The oxygen reduction storage system of claim 1, wherein the second internal collapsible blood container (202) comprises a microporous membrane selected from the group consisting of: polyvinylidene fluoride (PVDF) microporous membrane, polysulfone microporous membrane, polyolefin microporous membrane and polytetrafluoroethylene (PTFE) microporous membrane.

15. The oxygen reduction storage system of claim 1, wherein the first internal collapsible blood container (102) further includes a transparent window (112) on its surface.

16. The oxygen reduction storage system of claim 1, wherein the second internal collapsible blood container (202) further includes a transparent window (212) on its surface.

17. The oxygen-depleting storage system of claim 1, wherein the oxygen-consuming blood is stored in the anaerobic blood storage assembly (20) at a temperature of 4 to 6°C.

18. The oxygen-depleting storage system of any one of claims 1 to 17, wherein the oxygen-consuming blood in the second internal collapsible blood container (202) is maintained at an oxygen partial pressure (PO2) of less than 15 mmHg during a storage period of up to 64 days.

19. The oxygen-depleting storage system of any one of claims 1 to 17, wherein the oxygen-consuming blood in the second internal collapsible blood container (202) has an oxygen saturation (SO2) of less than 20%.

20. The oxygen reduction storage system according to any one of claims 1 to 17, wherein i. The first oxygen adsorbent (103) is sealed in one or more small bags; ii. The second oxygen adsorbent (207) is sealed in one or more small bags; or iii. i and ii.

21. The oxygen reduction storage system according to any one of claims 1 to 17, wherein i. The volume of the first top space is 10 to 1000 milliliters (mL); ii. The volume of the second headspace is 10 to 1000 ml; or iii. i and ii.

22. The oxygen reduction storage system according to any one of claims 1 to 17, wherein each of the open spaces (111) has a diameter greater than 0.75 square millimeters (mm²). 2 The area of ​​).

23. The oxygen reduction storage system according to any one of claims 1 to 17, wherein i. The first mesh or pad spacer (110) is a molded pad, woven pad, nonwoven pad, twisted yarn, or twisted pad; ii. The second mesh or pad spacer (213) is a molded pad, woven pad, nonwoven pad, stranded yarn, or stranded pad; or iii. i and ii.

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