ES2675049T3 - Blood separation apparatus - Google Patents

Abstract

An apparatus including: a cassette (1100) for controlling the movement of blood and separate blood components during an extracorporeal treatment session; and a centrifugal vessel (10A) including a rotational axis (11A); including the cassette (1100): a rigid plastic housing (1101) having an upper section (113) and a lower section (1131), together forming the upper section and the lower sections an interior space; a cube (1140) within the interior space; flexible tubes connected to the hub (1140); loops (1120, 1121, 1122, 1123, 1124) formed of flexible tubes, each of the loops being adapted to engage a peristaltic pump head (1301, 1302, 1303, 1304, 1305); an opening (1157); and a flexible tube section including tubes (1114, 1106, 1109), other than loops (1120, 1121, 1122, 1123, 1124), passing through the opening (1157) so that the flow of fluid through can be closed through the flexible tube section (1114, 1106, 1109) by the pressure exerted on the flexible tube section (1114, 1106, 1109); Including the centrifugal vessel (10A): an outer housing (100A), a connecting sleeve (500A), an upper core (200A), a lower core (201A), and a housing floor (180A), where the outer housing (100A) is made of a biocompatible transparent plastic material so that the upper and lower cores (200A, 201A) are visible through, where the outer housing (100A) is connected to the housing floor (180A), including the floor of housing (180A) projections (150A) to block the container (10) in a rotational device (900A), where the upper core (200A) and the lower core (201A) are separate components and where the lower surface (297A) of the core upper (200A) is in direct contact with an upper surface area (309A) of the lower core (201A), where a space between the outer housing (100A) and each of the upper core (200A) and the lower core (201A) define a volume to separate ation (220A), and where a first flow channel (420A) passes through the upper core (200A) and fluidly interconnects with at least one channel (305A) that is located between the upper core (200A) and the lower core ( 201A) and extending radially in relation to the rotational axis (11A) and the separation volume (220A), the apparatus also including a plurality of inlet tubes (1107, 1108) and an outlet tube (1115) to couple the cassette (1100) to the centrifugal container (10A), where one of the inlet tubes (1107) returns blood components of lower density from the centrifugal container (10) to the cassette (1100), where another of the inlet tubes (1108 ) returns blood components of higher density from the centrifugal container (10A) to the cassette (1100), and where the outlet tube (1115) supplies whole blood from the cassette (1100) to the centrifugal container (10A) and can be fluidly connected with the separation volume (220A) by the first flow channel (420A) and at least one channel (305A).

Description

Blood separation apparatus

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disposable photopheresis kit, the different devices that constitute the disposable kit, and the corresponding treatment process. The outline of the written description is as follows:

I. Disposable photopheresis kit

A. Cassette to control fluid flow

1. Filter set

B. Irradiation chamber

C. Centrifuge container

1. Drive tube

II.

 The permanent tower system

TO.

 Photoactivation camera

B.

 Centrifugal chamber

C.

 Fluid flow control cover

one.

 Cassette Fixation Mechanism

2.

 Automatic loading peristaltic pumps

D. Infrared communication

III. Photopheresis treatment process

The foregoing outline is included to facilitate the understanding of the features of the present invention. The outline does not limit the present invention and is not intended to categorize or limit any aspect of the invention. The inventions are described and illustrated in sufficient detail so that those skilled in this art can make them and use them easily. However, several alternatives, modifications, and improvements will be readily apparent without departing from the scope of the invention defined in the claim. Specifically, although the invention is described in the context of a disposable kit and permanent blood movement system for use in photopheresis therapy, some aspects of the invention are not limited thereto and are applicable to kits and systems used to carry out other therapies, such as apheresis or any other extracorporeal blood therapy.

1. Disposable photopheresis kit

Figure 1 illustrates a disposable photopheresis kit 1000 that performs the characteristics of the present invention. A new sterile disposable kit must be used for each therapy session. In order to facilitate the circulation of fluids through the photopheresis kit 1000, and to treat blood fluids circulating therethrough, the photopheresis kit 1000 is installed in a permanent tower system 2000 (Figure 17). The installation of 1000 photopheresis kit in the 2000 tower system is described in detail below.

The photopheresis kit 1000 includes a cassette 1100, a centrifuge container 10, an irradiation chamber 700, hematocrit sensor 1125, removable data card 1195, treatment bag 50, and plasma collection bag

51. The photopheresis kit 1000 further includes a saline connection peak 1190 and anticoagulant connection peak 1191 to respectively connect saline bags and anticoagulant fluid (not shown). The 1000 photopheresis kit has all the tubes and connectors necessary to fluidly connect all the devices and route the flow of fluids during a photopheresis treatment session. All tubes are sterile flexible tubes of medical quality. 1192 three-port connectors are arranged in various positions for the introduction of fluids into the tubes, if necessary.

Needle adapters 1193 and 1194 are arranged to respectively connect the photopheresis kit 1000 to needles to aspirate whole blood from a patient and return blood fluids to the patient. Alternatively, the photopheresis kit 1000 may be adapted to use a single needle to take whole blood from the patient and return the blood fluids to the patient. However, a two-needle kit is preferred because of the ability to simultaneously take whole blood and return blood fluids to the patient. When a patient is connected to the photopheresis 1000 kit, a closed loop system is formed.

Cassette 1100 acts as a tube organizer and a fluid flow router. The irradiation chamber 700 is used to expose blood fluids to UV light. The centrifuge container 10 separates the whole blood in its

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Preferably, a male projection 1136 is located at or near each of the four base corners 1130 and near the filter 1500. Male projections 1136 mate with the female holes 1161 to form a secure and snap-fit base 1131 with the cover 1130.

The base 1131 further includes a hub 1140. The hub 1140 is a five-way tube connector used to connect five tubes of the internal tubular circuitry. Preferably, three holes 1137 are located near and surrounding three tubes leading to the hub 1140. The hub 1140 acts as a centralized joint that can be used, in conjunction with compression actuators 1240-1247 (Figure 22), to direct fluids through of the 1000 yay photopheresis kit from the patient. In addition to the hub 1140, appropriate tube connectors, such as T-connectors 1141 and a Y-connector 1142, are used to obtain the desired paths of the flexible tubes.

Five holes 1137 are located on the floor of the base 1130. Each hole 1137 is surrounded by a hole wall 1138 having slots 1139 to pass portions of the internal tubular circuitry therethrough. An elongated hole 1157 is also disposed in the base floor 1131. Holes 1137 are located in the base 1131 to align with corresponding compression actuators 1243-1247 of the cover 1200 (Figure 22). The hole 1157 is located in the base 1131 for alignment with compression actuators 1240-1242 of the cover 1200 (Figure 22). Each hole 1137 is sized so that a single compression actuator 1243-1247 can extend therethrough. The hole 1157 is sized so that three compression actuators 1240-1242 can extend therethrough. Compression actuators 1240-1247 are used to close / occlude and open certain fluid passages of the internal tubular circuitry in order to facilitate or prohibit the flow of fluid along a desired path. When it is desired to have a certain open passage so that fluid can flow through it, the compression actuator 1240-1247 for said passage is in a lowered position. However, when it is desired to close a certain fluid passage so that no fluid can flow through it, the appropriate compression actuator 1240-1247 is raised, extending the compression actuator 1240-1247 through the hole 1137 or 1157 and compressing a portion of the flexible tubular circuitry against the lower surface 1160 (figure 5) of the cover 1130, thereby closing said passage. Preferably, occlusion bars 1163 and 1173 (Figure 5) are placed on the lower surface 1160 for alignment with compression actuators 1240-1247 so that the portion of occluded flexible tubes is compressed against occlusion bar 1163 or 1173. Alternatively, the occlusion bar can be omitted or placed in the compression actuators themselves.

It is preferable that the cassette 1100 has a unique identifier that can communicate and transmit information to the permanent tower system 2000. The unique identifier is provided in order to ensure that the disposable photopheresis kit is compatible with the blood movement equipment in the that is being charged, and that the photopheresis kit is capable of carrying out the desired treatment process. The unique identifier can also be used as means to ensure that the disposable photopheresis kit is of a certain name or trademark. In the illustrated example, the unique identifier is made as a data card 1195 (figure 2) that is inserted into the data card receiving port 2001 of the permanent tower system 2000 (figure 17). The 1195 data card has read and write capabilities and can store data related to the treatment therapy performed for future analysis. The unique identifier can also take several forms, including, for example, a microchip that interacts with the blood movement equipment when the kit is loaded, a barcode, or a serial number.

The cover 1130 has a data card holder 1134 to hold the data card 1195 (Figure 1). The data card holder 1134 includes four raised edges in a segmented rectangular shape to receive and secure the data card 1195 to the cassette 1100. The data card holder 1134 holds the data card 1195 in position by snap fit ( figure 2).

The internal cassette tubular circuitry 1100 will now be explained with reference to Figures 1 and 4. At least a portion of the internal tubular circuitry is preferably made of flexible plastic tubes that can be closed by exerting pressure without jeopardizing the hermetic integrity of the tube. The base 1131 of the cassette 1100 is illustrated in Figure 4 so that the internal tubular circuitry can be seen. The inlet tubes 1107 and 1108 and the outlet tube 1115 are intended to couple the cassette 1100 to the centrifuge vessel 10 (Figure 1). More specifically, the outlet tube 1115 is intended to deliver whole blood from the cassette 1100 to the centrifuge container 10, and the inlet tubes 1107 and 1108 are respectively provided to return blood components of lower density and blood components of higher density. high to cassette 1100 to direct them through the photopheresis 1000 kit. Blood components of lower density may include, for example, plasma, leukocytes, platelets, leukocyte layer, or any combination thereof. Higher density components may include, for example, red blood cells. The outlet tube 1117 and the inlet tube 1112 fluidly couple the cassette 1100 to the irradiation chamber 700. More specifically, the outlet tube 1117 is intended to supply a lower untreated blood component of density, for example, the leukocyte layer, to the irradiation chamber 700 for photoenergy exposure, while the inlet tube 1112 is intended to return the treated lower density blood component to the cassette 1100 for additional direction.

The inlet tube 1111 and the outlet tube 1116 couple the treatment bag 50 to the cassette 1100. The outlet tube 1116 is intended to deliver an untreated low density blood component, for example, the

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leukocyte layer, to the treatment bag 50. The outlet tube 1116 has a hematocrit sensor ("HCT") 1125 operatively connected thereto to monitor the introduction of a high density blood component, such as red blood cells. The HCT 1125 sensor is a photosensor assembly and is operatively coupled to a controller. The HCT 1125 sensor sends a detection signal to the controller when red blood cells are detected in the outlet tube 1116 and the controller will perform the appropriate action. The inlet tube 1111 is intended to return the untreated low density blood component from the treatment bag 50 to the cassette 1100 for additional direction. Inlet tubes 1109 and 1110 are respectively connected to saline and anticoagulant storage bags (not shown) by peaks 1190 and 1191 and are intended to deliver saline and an anticoagulant fluid to cassette 1100 to further direct them to the patient.

The inlet / outlet tube 1113 and the outlet tube 1118 attach the plasma collection bag 50 to the cassette 1100. More specifically, the outlet tube 1118 supplies a blood component, such as plasma, to the plasma collection bag 51. The inlet / outlet tube 1113 can be used to deliver red blood cells to the plasma collection bag 51 from the cassette 1100 or to return the blood component (s) that accumulates (n) in plasma collection bag 51 to cassette 1100 for additional address. Inlet tube 1106 and outlet tubes 1119 and 1114 are coupled to a patient. Specifically, the outlet tube 1114 is intended to return treated blood, saline, untreated blood components, treated blood components, and other fluids to the patient. The inlet tube 1106 is intended to deliver untreated whole blood (and a predetermined amount of an anticoagulant fluid) from the patient to the cassette 1100 for direction and treatment within the photopheresis kit 1000. The outlet tube 1119 is intended specifically to supply an anticoagulant fluid to the inlet tube 1106. It is preferable that all tubes be sterile disposable medical grade tubes. Flexible plastic tubes are the most preferred.

Cassette 1100 has five pump tube loops 1120, 1121, 1122, 1123, and 1124 to move blood fluids throughout the cassette 1100 and photopheresis kit 1000. More specifically, the pump tube loop 1121 loads the pump whole blood 1301 and introduces and removes, respectively, whole blood from the cassette 1100 by the inlet tube 1106 and the outlet tube 1115, passing through the filter 1500 along the entire path. The pump loop tube 1120 loads the return pump 1302 and moves blood fluids through the filter 1500 and brings them back to the patient through the outlet tube 1114. The pump loop tube 1122 loads the red blood cell pump 1305 and It takes red blood cells from the centrifuge container 10 and takes them to cassette 1100 via the inlet line 1108. The pump loop tube 1123 loads the anticoagulant pump 1304 and moves an anticoagulant fluid to the cassette 1100 by the inlet tube 1124 and takes it out of the cassette 1100 by the outlet tube 1119, which connects with the inlet tube 1106. The pump loop tube 1124 loads the recirculation pump 1303 and removes 1100 blood fluids, such as plasma, from the cassette, a through the treatment bag 50 and the irradiation chamber 700.

Each of the peristaltic pumps 1301-1305 is activated when necessary to perform photopheresis treatment therapy according to an embodiment of the method of the present invention described below in relation to Figures 26-27. Peristaltic pumps 1301-1305 can operate one at a time or in any combination. The pumps 1301-1305 work in conjunction with compression actuators 1240-1247 to direct fluids through desired paths of the photopheresis kit 1000. Holes 1137 and 1157 are strategically located at base 1131 along the internal tubular circuitry to Provide the appropriate address. Through the use of 1240-1247 compression actuators, fluids can be directed along any path or combination thereof.

1. The filter assembly

The filter 1500, which is located inside the cassette 1100 as described above, is illustrated in detail in Figures 6-10. With reference first to Figures 6 and 7, the filter 1500 is illustrated fully assembled. The filter 1500 includes a filter housing 1501. The filter housing 1501 is preferably made of a transparent or translucent plastic of medical quality. However, the invention is not limited thereto and the filter housing 1501 can be made of any material that does not contaminate blood or other fluids flowing through it.

The filter housing 1501 has four fluid connection holes leaving it, namely, a whole blood inlet port 1502, a whole blood outlet port 1503, treated fluid inlet port 1504, and an outlet port. 1505 treated fluid outlet. The 1502-1505 holes are standard medical tube connection holes that allow medical tubes to be fluidly connected. Holes 1502-1505 contain holes 1506, 1507, 1508 and 1509, respectively. Holes 1506, 1507, 1508 and 1509 extend through holes 1502, 1503, 1504 and 1505, forming fluid passages to the filter housing. 1501 in the desired positions.

Holes 1502, 1503, 1504 and 1505 are also used to fix filter 1500 inside cassette 1100. In doing so, holes 1502, 1503, 1504 and 1505 can engage U-shaped fasteners 1135 of cassette 1100 (Figure 3 ). The filter housing 1501 also has a projection 1510 extending from the bottom surface of the floor 1518 of the housing. The projection 1510 fits into a guide hole of the base 1131 of the cassette 1100 (Figure 3).

Referring now to Figure 8, filter 1500 is illustrated in an exploded state. The 1501 filter housing is

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from leukocyte-rich blood to irradiation and reduce the effects of self-binding typical of the lower surface area / volume ratios. The cross-sectional shape of the channel 715 is substantially rectangular (for example, rectangular, rhomboid or trapezoidal) which has as its long side the distance between the partition 720 and the distance between the plates as its short side. The shape of the cross section is designed for optimal irradiation of the cells that pass through the channel 715. Although a coil path 710 is preferred in order to avoid or minimize the areas of stagnant flow, other arrangements are contemplated.

The irradiation chamber 700 allows the efficient activation of photoactivatable agents by irradiation from a set of lights, such as the two banks of UVA PHOTOSETTE® lamps (758) for activation (Figure 16). The irradiation plate and the UVA light assembly (759) are designed for use in a position where edge 706 is facing down and edge 707 points up. In this orientation, the fluids entering the inlet port 705 can exit the outlet port 730 with the aid of gravity. In the most preferred embodiment, irradiation of both sides of the irradiation chamber takes place simultaneously while allowing easy removal of the chamber. The UVA 759 light assembly is located within the UV 750 chamber of the 2000 permanent tower system (figures 17 and 18).

The fluid path of the irradiation chamber forms loops to form two or more channels where blood enriched with leukocyte circulates during photoactivation by UVA light. Preferably, the irradiation chamber 700 has between 4 and 12 channels. More preferably, the irradiation chamber has 6 to 8 channels. Most preferably, the irradiation chamber has 8 channels.

Figure 14 depicts cut views of the irradiation chamber. The channels 715 of the coil path 710 are formed by the union of the raised partition 720 and the perimeter 726 of the plates.

The irradiation chamber of the present invention can be made of a biocompatible material and can be sterilized by known methods such as heating, radiation exposure or treatment with ethylene oxide (ETO).

The method of irradiating cells using the irradiation chamber 700 will now be explained during extracorporeal treatment of cells with electromagnetic radiation (UVA) to be used in the treatment of a patient (such as to induce apoptosis in the cells and deliver the cells to the patient) . Preferably the treated cells will be white blood cells.

In one embodiment of this method, a photoactivable or photosensitive compound is first supplied to at least a portion of the blood of a recipient before extracorporeal treatment of the cells. The photoactivable or photosensitive compound can be administered in vivo (for example, orally or intravenously). The photosensitive compound, when administered in vivo, can be administered orally, but can also be administered intravenously and / or by other conventional routes of administration. The oral dose of the photosensitive compound may be in the range of about 0.3 to about 0.7 mg / kg, more specifically about 0.6 mg / kg.

When administered orally, the photosensitive compound can be administered at least about one hour before the photopheresis treatment and no more than about three hours before the photopheresis treatment. If administered intravenously, times would be shorter. Alternatively, the photosensitive compound can be administered before or simultaneously with exposure to ultraviolet light. The photosensitive compound can be administered to whole blood or a fraction thereof provided that white blood cells or blood components receive the photosensitive compound. A portion of the blood could first be processed using known methods to substantially remove the erythrocytes and the photoactive compound can then be administered to the resulting leukocyte enriched fraction. In one embodiment, blood cells include white blood cells, specifically, T cells.

The photoactivable or photosensitive compound may be able, in the case of some psoralens, to bind to nucleic acids upon activation by exposure to electromagnetic radiation of a preset spectrum, for example, ultraviolet light.

Photoactive compounds may include, but are not limited to, compounds known as psoralen (or furocoumarins) as well as derivatives of psoralen such as those described, for example, in U.S. Patent No. 4,321,919 and U.S. Patent No. 5,399. 719 Photoactivatable or photosensitive compounds that can be used in accordance with the present invention include, but are not limited to, psoralen and psoralen derivatives; 8-methoxypsoralen; 4,5'8-trimethylpsoralen; 5-methoxy-psoralen; 4-methylpsoralen; 4,4-dimethylpsoralen; 4-5'-dimethylpsoralen; 4'-aminomethyl-4,5 ', 8-trimethylpsoralen; 4'-hydroxymethyl4,5 ', 8-trimethylpsoralen; 4 ', 8-methoxypsoralen; and a 4 '- (omega-amino-2-oxa) alkyl-4,5', 8-trimethylpsoralen, including but not limited to 4 '- (4-amino-2-oxa) butyl-4,5', 8- trimethylpsoralen. In one embodiment, the photosensitive compound that can be used includes the psoralen derivative, amotosalene (S-59) (Cerus, Corp., Concord, CA). See, for example, U.S. Patent Nos. 6,552,286, 6,469,052 and 6,420,570. In another embodiment, the photosensitive compound that can be used according to the invention includes 8-methoxypsoralen.

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channel 402A extending from the upper surface 298A of the upper plate 299A. The channel wall 401A is supported by a plurality of fins 251A that are attached to the surface of the inner wall 210C of the outer core wall 210A and the inner surface 205C of the upper core end 205A, and the channel wall 402A is supported by a plurality of fins 403A (figure 40). You can easily see that the height of lumen 400A can be adjusted by changing the sizes and shapes of core 200A, channel wall 401A, channel wall 402A, duct wall 325A, and height of duct wall 324A .

As illustrated in Figure 38, the lumen 400A, from the upper lumen end 480A to the lower lumen end 402C, encloses an inner lumen 400B. The lower lumen end 402C has a hole 303A that is in fluid communication with the separation volume 220A through several channels 305A. In the illustrated embodiment, lumen 400A includes a first container channel 420A. A second container channel 410A is located within the first container channel 420A of the upper core 200A and is enclosed therein from the end of lumen 480A and to lumen 402C. In addition, the second container channel 410A forms a passage through the lumen 400B from below the lower plate 300A for the extraction of a first separate fluid component 810 which is collected in the indentation 185A of the housing floor 180A. The second container channel 410A extends from the housing floor 180A of the outer housing 100A through lumen 400B and to the conduit channel 760A of the external conduit 20A.

Referring to Figure 38 (depicted without conduit 321C), the inner lumen 400B allows red blood cells 810 to exit the container 10A through a second container channel 410A that provides fluid communication from the housing floor above the indentation 185A to the hole 324E. The inner lumen 400B has an upper duct end 325C and a lower duct end 324B and includes two duct walls 324A and 325A that are tightly connected to the fluids and form the second container channel 410A having a smaller diameter and is separate and distinct from the first container channel 420A. The duct wall 325A is supported by a fin 251A that extends through the channel wall 401A and joins the duct wall 325A. Unlike lumen 400A which has an end near indentation 186A, lumen 400B extends beyond indentation 186A and through the lower plate 300A. The first conduit wall 325A has an upper end 325C having a hole 325D in the upper surface 482A of the lumen connector 481A and a lower end 325B having a hole 325E adapted to fit tightly with the upper end 324C of the conduit wall 324A. The upper end 324C of the conduit wall 324A is higher than the indentation 186A and has a hole 324D. The conduit wall 324A also has a lower end 324B and is supported by a plurality of fins 252A. The lower end 324B having a hole 325E is adapted to be connected to the conduit 320A having a hole 302A located near the center of the lower plate 300A. The connection of the holes 325E and 302A realizes the fluid communication between the lumen 400B and the space 220C between the lower plate 300A and the housing floor 180A. The space 220C between the lower plate 300A and the housing floor 180A, in turn, has fluid communication with the separation volume 220A.

The conduit 320A makes a tight fit with the lower end 324B, providing support to the second container channel 410A. Each container channel 420A and 410A can be made of any type of flexible or rigid tube (such as medicine tubes) or other device that provides a sealed passage, possibly for pressurized or depressurized fluid flow, and which can preferably be disposable and sterilizable, that is, simple and efficient manufacturing.

1. Drive tube

As illustrated in Figures 39A and 39B, the duct assembly 860A is attached to the container 10A by the connecting sleeve 500A which is attached on the first end 861A of the outer conduit 20A having a first conduit channel 780A, a second channel of duct 760A, and a third duct channel 770A. Each duct channel has fluid communication with a first container channel 420A, a second container channel 410A, and a container chamber 740A. The three duct channels are equally spaced 120 ° and have the same diameter in the outer duct 20A (see Figure 50). When fluidly connects with the external conduit 20A and container 10A, the conduit channel 780A fluidly connects with the first container channel 420A to introduce fluid 800 through the external conduit 20A to the container 10A for separation. Similarly, the second conduit channel 760A fluidly connects with the second container channel 410A to remove the first separate fluid component 810 from the container 10A to the external conduit 20A. Finally, the third conduit channel 770A connects with the container chamber 740A to remove the second separate fluid component 820 from the container 10A.

As illustrated in Figure 45, the outer conduit 20A has a connection sleeve 500A at the first end 861A and an anchor sleeve 870A at the second end 862A of the external conduit 20A. Between the connection sleeve 500A and the anchor sleeve 870A in the outer conduit 20A there is optionally a first projection 882 and a second projection 884 that extend perpendicularly from the outer conduit 20A and are of larger diameter. Between the connection sleeve 500A and the anchor sleeve 870A (or, if present, the first and second projection 882, 884) there is a first and a second support ring 871A and 872A. The external conduit 20A, the anchor sleeve 870A and the connection sleeve can be made of the same or different biocompatible materials of adequate strength and flexibility for use in this type of tubes in a centrifuge (a material

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preferred is HYTREL®). The connection sleeve 500A and the anchor sleeve 870A can be joined through any suitable means such as adhesives, welding, etc .; however, to facilitate manufacturing it is preferred that the connection sleeve 500A and the anchor sleeve 870A be overmolded to the outer conduit 20A.

With reference to Figures 45, 48 and 49, the anchor sleeve 870A includes a body 877B having a first anchor end 873A and a second anchor end 874A. The anchor sleeve 870A is attached to the second conduit end 862A of the outer conduit 20A (preferably by overmolding) and increases the diameter from the first ring 873A to the ring 874A. Distally spaced from the second end 874A is a ring 886A, which extends perpendicularly to the body 877B and of greater diameter than the body 877B of the anchor sleeve 870A. A plurality of ribs 877A having a first nerve end 877B between the ring 886A and the second anchor end 873A and a second nerve end 877C extending beyond the first anchor end 873A are attached to the body 877B. The second rib ends 877C are joined together by a ring 880A, which is also connected to the outer conduit 20A. The ribs 877A extend parallel to the external conduit 20A and are preferably placed over the region where the conduit channels 760A, 770A, and 780A are closest to the surface of the external conduit 20A (Figure 50). Regions where duct channels 760A, 770A and 780A are closer to the outer diameter of outer duct 20A unless reinforced, tend to fail during high speed rotation. The provision of parallel ribs with the duct channels beyond the anchor sleeve end 873A provides reinforcement to this region and prevents duct failure at high speed rotation. In one aspect, the ribs prevent buckling of the outer conduit 20A in this region and act as structural elements to transfer the torsional stress to the anchor sleeve 870A.

The connection sleeve 500A includes a body 830A having an upper sleeve end 831A and a lower sleeve end 832A (Figures 46 and 47). The lower sleeve end 832A has a sleeve flange 790A and a plurality of projections 843A, which are sized to engage indentations 484A on the wall surface 482A of the lumen connector 481A. When the container 10A is mounted, a fluid tight seal can be obtained by placing the O-ring 791A around the body 830A and compressing the O-ring 791A between the flange 790A and the housing 100A. The upper end of sleeve 831A is adapted to be fixed to the outer conduit 20A. With reference to Figures 46, 39A and 39B, the connection sleeve 500A is fixed to the container 10A by means of the sleeve flange 790A and is adapted to fluidly connect the conduit channels 780A, 760A, 770A of the external conduit 20A a container channels 420A and 410A, and chamber 740A of container 10A. When mounted, connection sleeve 500A is mounted on lumen connector 481A (Figures 39A and 39B).

The connecting sleeve 500A preferably increases in diameter from the upper end of the sleeve 831A to the lower end of the sleeve 832A and is overmolded to the first conduit end 861A of the outer conduit 20A. The connection sleeve 500A connects the container 10A to the external conduit 20A without using a rotary seal, which would normally be placed between the container 10A and the connection sleeve 500A. The non-tight connection between the container 10A and the connecting sleeve 500A can occur, as explained above, alternatively by the use, for example, of an O-ring, a groove, or lip, connection of the type of rubber washer , welding, or a tight fit with or without adhesive on container 10A or connection sleeve 500A.

As illustrated in Figures 46 and 39B, the sleeve flange 790A has a lower surface 847A that contacts the upper surface 482A of the lumen connector 481A forming a tight seal. However, the lumen connector 481A has a plurality of indentations 483A that perform fluid communication between the separation chamber 220A and the container chamber 740A, which, in turn, has fluid communication with the conduit channel 770A. The container chamber 740A is defined by the lumen mounting recess 851A and the upper surface 482A of the lumen connector 481A, excluding the space occupied by the hollow cylinders 321A and 322A. A plurality of protrusions 843A on the bottom surface 847A of the sleeve flange 790A engage and slide indentations 484A into the wall surface 482B of the lumen connector 481A, thus making a tight fit.

The connecting sleeve 500A helps to fix the outer conduit 20A to the container 10A, thereby fluidly connecting the outer conduit 20A to the container 10A. This fluid connection allows fluid 800 to be supplied through the external conduit 20A to the container 10A. Likewise, this fluid connection also allows separate fluid components 820 to be removed from the container 10A through the external conduit 20A.

The outer conduit 20A has an approximately constant diameter that helps reduce stiffness. An excessively rigid outer conduit 20A will heat up and fail faster. In addition, a constant-diameter conduit is cheap / easy to manufacture, allows easy experimentation with sizes of connection sleeve 500A and anchor sleeve 870A, and allows easy sliding of support rings 871A, 872A on top. The movement of the supports 871A and 872A will preferably be retained by first and second projections 882A and 884A. The outer conduit 20A can be made of any type of flexible tubes (such as medicine tubes) or other device that provides a sealed passage for fluid flow, which can be pressurized, to or from a reservoir of any kind, and which can be preferably disposable and sterilizable.

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II. The permanent tower system

Figure 17 illustrates the tower system 2000. The tower system 2000 is the permanent (i.e., non-disposable) equipment that receives the various devices of the photopheresis kit 1000, such as cassette 1100, irradiation chamber 700, and the centrifuge container 10 (figure 1). The tower system 2000 performs the regulation, pumping and general control and movement of the fluid flow through the disposable photopheresis kit 1000. The tower system 2000 automatically performs all necessary control functions by using a controller properly programmed, for example, a processor or IC circuit, coupled to all necessary components. Although a new disposable kit must be discarded after each photopheresis therapy session, the 2000 tower system is used several times. The 2000 tower system can be modified to perform various extracorporeal blood circuit treatments, for example, apheresis, by properly programming the controller or changing some of its components.

The tower system 2000 has a housing that has an upper portion 2100 and a base portion 2200. The base portion 2200 has an upper portion 2201 and a lower portion 2202. Wheels 2203 are arranged at or near the lower portion 2202 of the base portion 2200 so that the tower system 2000 is mobile and can be easily moved from one room to another in a hospital. Preferably, the front wheels 2203 are pivotable about a vertical axis to facilitate the direction and handling of the tower system 2000. The upper part 2201 of the base portion 2200 has an upper surface 2204 having a control cover 1200, better illustrated in figure 22, constructed therein (see figure 22). In Figure 17, the cassette 1100 has been loaded onto the control cover 1200. The base portion 2200 also has hooks (not shown), or other connectors, for hanging a plasma collection bag 51 and a treatment bag 50 Such hooks may be located anywhere in the tower system 2000 provided that their position does not interfere with the operation of the system during therapy. The base portion 2200 has a photoactivation chamber 750 (Figure 18) located behind the door 751. Additional hooks (not shown) are arranged in the tower system 2000 to hang saline and anticoagulant bags. These hooks are preferably placed in the upper portion 2100.

The photoactivation chamber 750 (Figure 18) is arranged in the base portion 2200 of the tower system 2000 between the upper part 2201 and the lower part 2202 behind the door 751. The door 751 is hingedly connected to the base portion 2200 and is intended to access the photoactivation chamber 750 and so that the operator can close the photoactivation chamber 750 so that no UV light escapes into the environment during treatment. The recess 752 is provided so that tubes 1112, 1117 (Figure 1) can pass to the photoactivation chamber 750 when the irradiation chamber 700 is loaded and when the door 751 is closed. The photoactivation chamber is explained in detail below with respect to Figures 16 and 18.

The upper portion 2100 is located above the base portion 2200. The centrifuge chamber 2101 (Figure 19) is located in the upper portion 2100 behind the door 2102 of the centrifuge chamber. The door 2102 of the centrifuge chamber has a window 2103 so that the operator can see the centrifuge chamber 2101 and monitor the problems. The window 2103 is glass thick enough to withstand the forces that can be exerted in the event of an accident during centrifugation that the centrifuge vessel can rotate at speeds greater than 4800 RPMs. Preferably, window 2103 is made of shockproof glass. Door 2102 is articulated connected to the upper portion 2100 and has an automatic locking mechanism that is activated by the system controller during system operation. Centrifugal chamber 2101 is explained in more detail below with respect to Figure 19.

The cover 1200 is preferably placed on the upper surface 2204 of the base portion 2200 at or near the front of the tower system 2000 while the upper portion 2100 extends upward from the base portion 2200 near the rear of the tower system 2000. This allows the operator easy access to the control cover 1200 while simultaneously providing access to the centrifuge chamber 2101. Designing the tower system 2000 so that it has the centrifuge chamber 2101 in the upper portion 2100 and the photoactivation chamber 750 and the cover 1200 in the base portion 2200, a vertical configuration is achieved. As such, the 2000 tower system has a size that occupies little space and occupies a reduced space on the valuable floor of the hospital. The height of the 2000 tower system remains below sixty inches so that the view is not obstructed when transporting the machine through the hospital from behind. Additionally, the provision of the cover 1200 in a fairly horizontal position provides the operator with a position to place the photopheresis kit 1000 devices while loading other devices, facilitating loading. The 2000 tower system is robust enough to resist forces and vibrations produced by the centrifugation process.

A monitor 2104 is disposed at the door 2102 of the centrifugal chamber above the window 2103. The monitor 2104 has a display area 2105 to visually present data to the operator, such as, for example, user interfaces for data entry, loading instructions, graphics, warnings, alerts, therapy data, or therapy progress. Monitor 2104 is coupled and is controlled by the system controller. A data card receiving port 2001 is arranged on one side of the monitor 2104. The data card receiving port 2001 is intended to slidably receive the data card 1195 that is supplied with each disposable photopheresis kit 1000 (Figure one). As mentioned above, data card 1195 may be preprogrammed to store various data to be supplied to the tower system 2000 controller. For example, the

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data card 1195 may be programmed to transmit information so that the system controller can ensure: (1) that the disposable photopheresis kit is compatible with the blood movement equipment in which it is loaded; (2) that the photopheresis kit is capable of carrying out the desired treatment process; (3) that the disposable photopheresis kit be of a certain brand or manufacture. The data card receiving port 2001 has the hardware and circuitry necessary to read and write data on the data card 1195. Preferably, the data card receiving port 2201 will record treatment therapy data on the data card. data 1195. Such information may include, for example, collection hours, collection volumes, treatment times, volumetric flow rates, alarms, malfunctions, disturbances in the process, or any other desired data. Although the data card reception port 2001 is arranged on the monitor 2104, it can be located anywhere in the tower system 2000 provided it is coupled to the system controller or other appropriate control means.

A. Photoactivation chamber to receive the irradiation chamber

With reference now to Figures 16 and 18, the photoactivation chamber 750 is illustrated in cross section. The photoactivation chamber 750 is formed by the housing 756. The housing 756 fits inside the base portion 2200 of the tower system 2000 behind the door 751 (Figure 17). The photoactivation chamber 750 has a plurality of electrical connection holes 753 arranged in the rear wall 754. The electrical connection holes 753 are electrically coupled to an electrical power source. The photoactivation chamber 750 is designed to receive the UVA 759 light assembly (figure 16). When fully charged in the photoactivation chamber 750, the electrical contacts (not shown) located on the contact wall 755 of the UVA light assembly 759 form an electrical connection with electrical connection holes 753. This electrical connection allows electrical power to be supplied to UVA 758 lamps so that they can be activated. Preferably, three electrical connection holes are provided for each set of UVA lamps 758. More preferably, the UVA light set 759 has two sets of UVA lamps 758 forming a space into which the irradiation chamber 700 can be inserted. Electricity supply to the UVA 758 lamps is controlled by the system controller properly programmed using a switch. UVA 758 lamps are activated and deactivated when necessary by the controller during the photopheresis therapy session.

The ventilation hole 757 is arranged in the upper part of the housing 756 near the rear wall 754 of the photoactivation chamber 750. The ventilation hole 757 connects with the ventilation duct 760 leaving the rear part of the tower system 2000 When the heat generated by the UVA 758 lamps accumulates in the photoactivation chamber 750 during a treatment therapy, this heat escapes from the photoactivation chamber 750 through the ventilation hole 757 and the ventilation duct 760. The heat leaves the 2000 tower system through the 761 tower housing hole located at the rear of the 2000 tower system, away from the patient and the operator.

The photoactivation chamber 750 also includes the tract 762 to receive the irradiation chamber 700 and maintain the irradiation in an upright position between the UVA lamps 758. The tract 762 is at or near the bottom of the photoactivation chamber 750. Preferably , a leak detector circuit 763 is arranged below the tract 762 to detect fluid leaks from the irradiation chamber 700 during, before or after the operation. The leak detector circuit 762 has two U-shaped electrodes located in a flexible circuit reinforced with adhesive. The electrodes are designed to allow the application of a short circuit to test for discontinuities. One end of each electrode goes to an integrated circuit while the other end of each electrode is attached to a solid state switch. The solid state switch can be used to check the continuity of the electrodes. By closing the switch, the electrodes short-circuit each other. The integrated circuit then detects the short. The closing of the switch produces a situation equivalent to the humidification of the electrodes (that is, an escape). If the electrodes are damaged in any way, the continuity test will fail. This is a positive indication that the electrodes are not damaged. This test can be performed every time the system is started or periodically during normal operation to ensure that the leak detection circuit 762 works properly. The leak detection circuit 762 helps ensure that leaks do not go unnoticed during a complete therapy session because the leak detection circuit is damaged. An electrical diagram of the leak detector circuit 762 is shown in the figure

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B. Centrifugal chamber

Figure 19 illustrates the centrifugal chamber 2101 in cross section with the tower system housing 2000 removed. The rotational device 900 (also in cross-section) capable of using 1-omega 2-omega spin technology is placed inside the centrifuge chamber 2101. The rotational device 900 includes a rotating support 910 and a container holding plate 919 for fixing Rotating the centrifuge container 10 (Figure 1). The housing 2107 of the centrifugal chamber 2101 is preferably made of aluminum or some other light and resistant metal. Alternatively, other rotational systems can be used within the 2000 tower system such as that described in US Patent No. 3,986,442.

The leak detection circuit 2106 is arranged in the rear wall 2108 of the housing 2107. The circuit of

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Claims (1)

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