HK1080778B - Apparatus for separating components of a fluid - Google Patents

Description

Device for separating fluid components

RELATED APPLICATIONS

This application is a continuation-in-part application of U.S. patent application 10/375,628 filed on 27/2/2003 in the interest of U.S. provisional application serial No. 60/361,287 filed on 3/4/2002, both of which are hereby incorporated by reference in their entirety.

Technical Field

The present invention relates generally to methods and devices for separating fluids, such as biological or sensitive fluids, such as blood, into its various components. And more particularly to a method and apparatus for improving the yield of components by using centrifugal force to density separate a fluid into its various components.

Background

With the development of medicine, in a medical treatment, it is possible to treat the blood of a patient in a closed-loop process, returning the treated blood of the patient himself to the patient. Examples of such processes include external treatment of diseases in which an increased morbidity of lymphocytes is present, such as cutaneous T-cell lymphoma or other diseases affecting leukocytes. In these methods, the blood of a patient is irradiated with ultraviolet light in the presence of chemicals or antibodies. Ultraviolet light affects the binding between lymphocytes and chemicals or antibodies that inhibit the metabolic processes of lymphocytes.

During one of these medical procedures, blood is separated into red blood cells ("RBCs") and buffy coat using a centrifuge bowl, such as the Latham bowl disclosed in U.S. patent No.4,303,193, which is incorporated herein by reference in its entirety. The Latham bowl is a blood component separator that has been used for some time in medical apheresis, and is also used in innovative medical treatments such as extracorporeal photopheresis (ECP). PCT applications WO97/36581 and WO97/36634, and U.S. Pat. No.4,321,919; 4,398,906, respectively; 4,428,744 and 4,464,166 provide illustrations of extracorporeal light separation and are incorporated herein by reference in their entirety.

The efficiency of the Latham bowl is generally measured by the white blood cell ("WBC") yield, which is typically about 50%. Yield refers to the percentage between the number of cells collected and treated. This high throughput allows the Latham bowl separator to collect a larger volume of WBCs while processing less whole blood from the donor when compared to other types of whole blood separators. However, the main disadvantage of the Latham bowl separator is that once the RBCs and plasma fill the bowl, the separation process must be stopped repeatedly to remove the accumulated RBCs and plasma, resulting in a "batch-type" process. Although the Latham bowl has a high volumetric throughput, the continuous filling and emptying of the bowl wastes time; thus, the process is considered to be inefficient in terms of time. In addition, the Latham bowl requires a rotating seal, which is costly and difficult to manufacture.

A further disadvantage of centrifugal processing devices is their high manufacturing cost due to the need for precise tolerances, rotary seals and costly manufacturing processes.

Disclosure of Invention

The present invention provides an apparatus for separating components of a fluid, the apparatus comprising: a housing having an upper housing end and a lower housing end, wherein said housing increases in diameter from said upper housing end to said lower housing end, said lower housing end having a housing floor, said housing upper end having a housing outlet, said housing adapted to rotate about a central axis; the housing includes a core in the interior space; a core having an outer wall, an upper core end and a lower core end; the core is connected with the shell along with the rotation of the core; and providing a separation space between the core and the housing; the core end having a cavity connector and a cavity connector top surface; a first chamber for providing fluid communication from the housing outlet through the chamber connector and then radially outwardly through the wick to the fluid separation space; a second chamber providing fluid communication extending axially along the central axis from the housing outlet to the housing bottom; a connection sleeve forming a chamber with the chamber connector and providing fluid communication between the housing outlet and the separation space.

In another embodiment of the present invention, a method is provided for separating a fluid component into a higher density component and a lower density component, the method comprising: providing a centrifugal bowl having a first bowl channel, a second bowl channel, and a bowl cavity; flowing the fluid from a source through the first bowl channel into the centrifugal bowl; rotating the centrifuge bowl about an axis; removing said higher density component from said drum through said second drum passage; and removing the lower density component from the drum through the drum chamber.

Drawings

The invention is described in detail with reference to the drawings, which illustrate embodiments of the inventive devices, assemblies, systems and methods.

FIG. 1 is a schematic representation of a disposable kit embodiment of a photopheresis treatment incorporating features of the present invention;

FIG. 2 is a front perspective view of a cassette embodiment for controlling fluid flow into the disposable photopheresis kit of FIG. 1;

FIG. 3 is an exploded view of the cassette of FIG. 2;

FIG. 4 is a top view of the cassette of FIG. 2 with the cover removed and showing internal plumbing lines;

FIG. 5 is a bottom view of the lid of the box of FIG. 2;

FIG. 6 is an elevated perspective view of an embodiment of a filter assembly;

FIG. 7 is a bottom perspective view of the filter assembly of FIG. 6;

FIG. 8 is an exploded view of the filter assembly of FIG. 6;

FIG. 9 is a rear perspective view of the filter assembly of FIG. 6;

FIG. 10 is a schematic view of the filter assembly of FIG. 6 connected to a pressure sensor and a data processor;

FIG. 11 is a front view of the radiation chamber;

FIG. 12 is a side longitudinal view of the radiation chamber of FIG. 11;

FIG. 13 is a side transverse view of the radiation chamber of FIG. 11;

FIG. 14 is a cross-sectional view of portions of the first and second plates prior to being joined together to form the radiating cavity of FIG. 11;

FIG. 15 is a cross-sectional profile end view of the radiation chamber of FIG. 11;

fig. 16 is a perspective view of the radiation chamber of fig. 11 positioned within a UVA light assembly;

FIG. 17 is an elevated perspective view of an embodiment of a durable tower system for use with a disposable kit for photopheresis treatment;

FIG. 18 is a cross-sectional view of an embodiment of a light-activated chamber without a UVA light assembly for use in the tower system of FIG. 17;

FIG. 19 is a cross-sectional view of an embodiment of a centrifugal chamber for use in the tower system of FIG. 17;

FIG. 20 is a circuit diagram of a leak detection circuit provided within the light activation chamber of FIG. 18;

FIG. 21 is a circuit diagram of a leak detection circuit provided within the centrifuge chamber of FIG. 19;

FIG. 22 is an elevated perspective view of an embodiment of a fluid flow control panel of the tower system of FIG. 17;

FIG. 23 is a perspective bottom view of the control panel of FIG. 22;

FIG. 24 is an exploded view of the control panel of FIG. 22;

FIG. 25 is a top perspective view of the control panel of FIG. 22 with the cassette of FIG. 2 loaded thereon;

FIG. 26 is a flow diagram of an embodiment of a photopheresis process;

FIG. 27 is a schematic view of an embodiment of a fluid flow cycle for performing the process of FIG. 26;

FIG. 28 is a top perspective view of a peristaltic pump embodiment;

FIG. 29 is a cross-sectional side view of the peristaltic pump of FIG. 28;

FIG. 30 is a pre-perspective view of the rotor of the peristaltic pump of FIG. 29;

FIG. 31 is a bottom perspective view of the rotor of FIG. 30;

FIG. 32 is a top view of the peristaltic pump of FIG. 28;

FIG. 33 is a top view of the peristaltic pump of FIG. 28 in a loading position and adjacent to the cassette of FIG. 2.

Fig. 34 is a circuit diagram of an infrared communication port circuit;

FIG. 35 shows an embodiment of a centrifuge bowl and rotating frame;

FIG. 36 is a profile view of the drum of FIG. 35;

FIG. 37 is an exploded view of the bowl of FIG. 36;

FIG. 38 shows a cross-sectional view of the drum of FIG. 36 along line XIX-XIX;

FIG. 39A shows a cross-sectional view along line XX of a connection sleeve with the cavity connector of the barrel of FIG. 38 in place;

FIG. 39B shows another cross-sectional view of a connection sleeve in place with the lumen connector of the barrel of FIG. 38;

FIG. 40 shows a cross-sectional view of the top core of the drum of FIG. 37;

FIG. 41 shows a profile view of the top core and upper plate of FIG. 37;

FIG. 42 shows a bottom view of the top core of FIG. 41;

FIG. 43A shows an exploded profile view of the bottom core and lower plate of the bowl of FIG. 37;

FIG. 43B shows a profile cross-sectional view of the bottom core and lower plate of the bowl of FIG. 43A connected together;

FIG. 44 shows an exploded side view of the bottom core and lower plate of FIG. 43A;

FIG. 45 shows a profile view of another embodiment of a conduit assembly;

FIG. 46 shows a profile view of the coupling sleeve of FIG. 45;

FIG. 47 shows a profile view of one end of the conduit assembly of FIG. 45;

FIG. 48 shows a profile view of the fixed end of the present invention;

FIG. 49 shows a side cross-sectional view of the fixed end;

fig. 50 shows a horizontal sectional view of the fixed end along line XXI;

FIG. 51 shows a profile view of the rotating frame of FIG. 35;

FIG. 52 is an enlarged view of the retainer of the outer conduit;

FIG. 53 shows an alternative embodiment of a drum with a cross-section similar to that shown in FIG. 38;

FIG. 54 shows an alternative embodiment of a core;

fig. 55 shows an alternative embodiment of a connection sleeve.

Detailed Description

The technical features of the present invention are embodied in a durable blood-driven device, a disposable photopheresis kit, the various devices that make up the disposable kit, and the corresponding treatment procedures. The headings of the specification written hereinafter are as follows:

I. disposable photopheresis replacement tool

A. Cassette for controlling fluid flow

1. Filter assembly

B. Radiation cavity

C. Centrifugal rotating drum

1. Driving tube

Durable tower system

A. Light activated cavity

B. Centrifugal chamber

C. Fluid flow control panel

1. Box clamping mechanism

2. Self-loading peristaltic pump

D. Infrared communication

Photopheresis treatment procedure

The above headings are provided to facilitate an understanding of the technical features of the present invention. This heading is not limiting of the invention and is not meant to categorize or limit any aspect of the invention. The invention has been described and illustrated in sufficient detail to enable those of ordinary skill in the art to readily make and use them. It should be apparent, however, that various substitutions, modifications and improvements may be made thereto without departing from the spirit and scope of the invention. In particular, although the present invention is described in the context of a disposable kit and durable blood drive system for use in photopheresis, certain aspects of the present invention are not so limited, but rather may be used in kits and systems for performing other treatments, such as apheresis or any other extracorporeal blood treatment.

I. Disposable photopheresis replacement tool

FIG. 1 illustrates a disposable photopheresis kit 1000 embodying features of the present invention. A new disposable sterilization tool is required to be used at each treatment session. To facilitate circulation of fluid through photopheresis kit 1000 and treatment of blood fluid circulating therethrough, photopheresis kit 1000 is installed in durable tower system 2000 (FIG. 17). The installation of photopheresis kit 1000 in durable tower system 2000 is described in detail below.

Photopheresis kit 1000 includes cassette 1100, centrifuge bowl 10, radiation chamber 700, hematocrit sensor 1125, replaceable data card 1195, processing bag 50, and plasma collection bag 51. Photopheresis kit 1000 also includes saline connection rod 1190 and anticoagulant connection rod 1191 for connecting saline and anticoagulant fluid bags (not shown), respectively. Photopheresis kit 1000 has all the necessary tubing and connectors to fluidly connect to all devices and route fluid circulation during photopheresis treatment. All tubing is sterile flexible medical tubing. Three-way connectors 1192 are provided at various locations for introducing fluid into the tubing if desired.

Needle adapters 1193 and 1194 are provided to respectively couple photopheresis kit 1000 to needles for drawing whole blood from a patient and returning blood flow to the patient. Alternatively, photopheresis kit 1000 may use a single needle to both withdraw blood from the patient and return blood to the patient. However, to have the ability to simultaneously withdraw whole blood from a patient and return blood flow to the patient, a double needle tool is preferred. When a patient is connected to photopheresis kit 1000, a closed loop system is formed.

Cassette 1100 acts as both a tubing organizer and a fluid flow router. The radiation chamber 700 is used to expose the blood flow to ultraviolet light. The centrifuge bowl 10 separates whole blood into its various components according to density. The processing bag 50 is a 1000mL three port bag. The direct connection interface 52 is used to inject a light-activated or light-sensitive compound into the processing bag 50. The plasma collection bag 51 is a 1000mL double-port bag. Both the processing bag 50 and the plasma collection bag 51 have hinged spike tubes 53 that drain if necessary. Photopheresis kit 1000 also includes hydrophobic filters 1555 and 1556, which are adapted to couple pressure sensors 1550 and 1551 to filter 1500 via vent tubes 1552 and 1553 for monitoring and controlling the pressure within the tubes coupled to the patient (FIG. 10). Monitoring the pressure helps to ensure that the tool is operating within safe pressure limits. The various devices of photopheresis kit 1000 and their functions are described in detail below.

A. Cassette for controlling fluid flow

FIG. 2 shows a top perspective view of a disposable cassette 1100 for valving, pumping and controlling blood flow during a photopheresis procedure. Cassette 1100 has a housing 1101 forming an interior space for housing various internal components and tubular lines. The housing 1101 is preferably made of a hard plastic, but may be made of other suitable hard materials. Housing 1101 has side walls 1104 and a top surface 1105. Side wall 1104 of housing 1101 has tabs 1102 and 1103 extending therefrom. As best shown in FIG. 25, cassette 1100 needs to be secured to deck 1200 of tower system 2000 during the photopheresis process. Tabs 1102 and 1103 help position and secure cassette 1100 to panel 1200.

Cassette 1100 has fluid inlet tubes 1106, 1107, 1108, 1109, 1110, 1111, and 1112 for receiving fluid into cassette 1100, fluid outlet tubes 1114, 1115, 1116, 1117, 1118, and 1119 for expelling fluid from cassette 1100, and fluid inlet/outlet tube 1113 that can be used to introduce and expel fluid into and out of cassette 1100. These fluid input and output tubes fluidly connect cassette 1100 to the patient being treated, as well as the various devices of photopheresis kit 1000, such as centrifuge bowl 10, radiation chamber 700, treatment bag 50, plasma collection bag 51, and bags containing saline, anticoagulant, to form a closed loop external fluid circuit (FIG. 27).

Pump tube loops 1120, 1121, 1122, 1123, and 1124 protrude from side wall 1104 of housing 1101. Pump tube loops 1120, 1121, 1122, 1123, and 1124 are provided to facilitate circulation of fluid throughout photopheresis kit 1000 during treatment. More particularly, each of the pump tube loops 1120, 1121, 1122, 1123, and 1124 is loaded into a respective peristaltic pump 1301, 1302, 1303, 1304, and 1305 (FIG. 4) when the cassette 1100 is secured to the plate 1200 for operation. Peristaltic pumps 1301, 1302, 1303, 1304, and 1305 drive fluid through respective pump tube loops 1120, 1121, 1122, 1123, and 1124 in a predetermined direction to drive fluid through photopheresis kit 1000 (FIG. 1) as needed. The operation and automatic loading and unloading of peristaltic pumps 1301, 1302, 1303, 1304, and 1305 are described in detail below with reference to fig. 28-33.

Referring now to FIG. 3, cassette 1100 is shown exploded together with housing 1101. For ease of illustration and description, the internal piping within housing 1101 is not shown in fig. 3. This internal piping is shown in fig. 4 and will be discussed with reference to this figure. Cassette 1100 has a filter assembly 1500 positioned therein and in fluid communication with inlet tube 1106, outlet tube 1114, and one end of each pump tube loop 1120 and 1121. Filter assembly 1500 includes vent chambers 1540 and 1542. The filter assembly 1500 and its functions are discussed in detail below with reference to fig. 6-10.

Housing 1101 includes a cover 1130 and a base 1131. Cover 1130 has top surface 1105, bottom surface 1160 (fig. 5), and sidewalls 1104. Cover 1130 has openings 1132 and 1133 for allowing vent chambers 1540 and 1542 of filter assembly 1500 to protrude therethrough. The side wall 1104 has a number of tube slots 1134 to allow the inlet, outlet and pump loop tubes to pass through the interior space of the housing 1101. The connections to the internal tubular lines located there are only a few pipe slots 1134 labeled in fig. 3 to avoid crowding of the reference numerals. The tabs 1102 and 1103 are positioned on the side wall 1104 so as not to interfere with the tube slots 1134. Cover 1130 has closure bars 1162 and 1162A (fig. 5) extending from bottom surface 1160. In its formation, closure bars 1162 and 1162A are preferably molded into bottom surface 1160 of lid 1130.

Base 1131 has a plurality of U-shaped tube holders 1135 extending upwardly from top surface 1136. U-tube holder 1135 holds the inlet tube, outlet tube, pump loop tubing, filter assembly and inner tubular lines in place. Only a few U-tube holders 1135 are labeled in fig. 3 to avoid crowding of reference numerals. Preferably, a U-tube retainer 1135 is disposed on base 1131 at each of the inlet, outlet or pump loop tubes that pass through slots 1134 in side wall 1104. Protrusions 1136 project from top surface 1136 of base 1131 for engaging corresponding recesses 1161 (fig. 5) located in bottom surface 1160 of cover 1130. Preferably, protrusions 1136 are located at or near the four corners of base 1130 and are near filter 1500. Protrusion 1136 mates with recess 1161 to form a snap fit and secure base 1131 to cover 1130.

The base 1131 also includes a socket 1140. The receptacle 1140 is a five-way tube connector for connecting five tubes of an internal tubular line. Preferably, three holes 1137 are located adjacent to and surround three tubes that are introduced into the receptacle 1140. Receptacle 1140 functions as a centralized connection for mating with compression actuator 1240 and 1247 (FIG. 22) to direct fluid through photopheresis kit 1000 and to deliver fluid to or from a patient. Instead of the receptacle 1140, suitable tubing connectors, such as a T-connector 1141 and a Y-connector 1142, may be used to obtain the desired flexible tubing.

Five holes 1137 are located on the bottom surface of substrate 1130. Each bore 1137 is surrounded by a bore wall 1138 having a slot 1139 for passing the inner tubular line therethrough. An elongated aperture 1157 is also provided on the bottom surface of the base 1131. Apertures 1137 are located on bottom surface 1131 to align with corresponding compression actuators 1243 and 1247 on panel 1200 (FIG. 22). Apertures 1157 are located on base 1131 to align with corresponding compression actuators 1240 and 1242 on panel 1200 (fig. 22). Each aperture 1137 is sized so that a separate compression actuator 1243 and 1247 can extend therethrough. Aperture 1157 is sized so that three compression actuators 1240-1242 can extend therethrough. Compression actuators 1240 and 1247 are used to close/close and open certain fluid passages of the internal tubular line to facilitate or prevent fluid flow along a desired path. When a channel is required to be open so that fluid can flow therethrough, the compression actuator 1240-. Preferably, the closing bars 1163 and 1173 (FIG. 5) are positioned on the bottom face 1160 to align with the compression actuators 1240 and 1247 so that the portion of the flexible tubing system that is closed is pressed toward the closing bar 1163 or 1173. Alternatively, the closing rod may be omitted or located on the compression actuator itself.

Cassette 1100 preferably has a unique identifier that can exchange or communicate information to durable tower system 2000. Unique identification is provided to ensure that the disposable photopheresis kit is compatible with the blood drive equipment in which it is loaded and to ensure that the photopheresis kit is capable of running the desired procedure. The unique identifier can also be used as a means to ensure that the disposable photopheresis kit is of a certain brand and manufacture. In the example shown, the unique identifier embodies a data card 1195 (FIG. 2) that is inserted into data card port 2001 (FIG. 7) of durable tower system 2000. Data card 1195 has read and write capabilities and is capable of storing data for future analysis of associated treatment treatments. The unique identifier can also take various forms including, for example, a microchip, bar code, or serial number that interacts with the blood drive device when the tool is loaded.

Cover 1130 has data card holder 1134 for holding data card 1195 (FIG. 1). Data card holder 1134 includes four raised ridges in the shape of segmented rectangles for receiving and securing data card 1195 to cassette 1100. Data card holder 1134 holds data card 1195 in place via a snap fit (fig. 2).

Referring now to fig. 1 and 4, the internal tubular circuitry of cassette 1100 will now be discussed. At least a portion of the inner tubular line is preferably formed of a flexible plastic tube that can be compressed closed by pressure without compromising the sealing integrity of the tube. The base 1131 of the cassette 1100 is shown in FIG. 4 so that the internal tubular circuitry can be seen. Inlet tubes 1107 and 1108 and outlet tube 1115 are provided for connecting cassette 1110 to centrifuge bowl 10 (fig. 1). More specifically, outlet tube 1115 is provided for transferring whole blood from cassette 1100 to centrifuge bowl 10, and inlet tubes 1107 and 1108 are provided for returning the lower density blood components and the higher density blood components, respectively, to cassette 1100 for further transfer through photopheresis kit 1000. The lower density blood component may include, for example, plasma, leukocytes, platelets, buffy coat, or any combination thereof. The higher density components may include, for example, red blood cells. An outlet tube 1117 and an inlet tube 1112 fluidly connect the cassette 1100 to the radiation chamber 700. More particularly, an outlet tube 1117 is provided for delivering untreated lower density blood components, such as buffy coat, to the radiation chamber 700 for exposure to light energy. An inlet line 1112 is also provided for returning the processed lower density blood component to the cassette 1100 for further transfer.

An inlet tube 1111 and an outlet tube 1116 connect the processing bag 50 to the cassette 1100. An outlet tube 1116 is provided to deliver untreated low density blood components, such as buffy coat, to the processing bag 50. Outlet tube 1116 has a hematocrit ("HCT") sensor 1125 operatively connected thereto to monitor the introduction of high density blood components, such as red blood cells. HCT sensor 1125 is a light sensor assembly and is operatively connected to a controller. When red blood cells are detected in outlet tube 1116, HCT sensor 1125 sends a detection signal to the controller, and the controller will take appropriate action. For further transfer, an inlet tube is provided to return untreated low density blood components from the processing bag 50 to the cassette 1100. Inlet tubes 1109 and 1110 are connected to saline and anticoagulant storage bags (not shown) by staples 1190 and 1191, respectively, and inlet tubes 1109 and 1110 are provided for delivering saline and anticoagulant fluid to cassette 1100 for further delivery to a patient.

Inlet/outlet tube 1113 and outlet tube 1118 connect plasma collection bag 50 to cassette 1100. More particularly, outlet tube 1118 delivers blood components, such as plasma, to plasma collection bag 51. Inlet/outlet tube 1113 can be used to transfer red blood cells from cassette 1100 to plasma collection bag 51, or to return one or more blood components collected in plasma collection bag 51 to cassette 1100 for further transfer. Both inlet tube 1106 and outlet tubes 1119 and 1114 are connected to the patient. In particular, outlet tube 1114 is provided to return treated blood, saline, untreated blood components, treated blood components, and other fluids to the patient. For routing and processing in the light processing tool 1000, an inlet tube 1106 is provided for transferring untreated whole blood (and a predetermined amount of anticoagulant fluid) from a patient to the cassette 1100. An outlet tube 1119 is specifically provided for delivering anticoagulant fluid to inlet tube 1106. Preferably, all tubing is disposable sterile medical tubing. Flexible plastic tubing is most preferred.

Cassette 1100 has five pump tube loops 1120, 1121, 1122, 1123, and 1124 for driving fluid throughout cassette 1100 and photopheresis kit 1000. More particularly, pump tube loop 1121 loads whole blood pump 1301 and drives whole blood into or out of cassette 1100 through inlet tube 1106 and outlet tube 1115, respectively, and along the way through filter 1500. Pump loop tube 1120 loads into return pump 1302, driving blood flow through filter 1500 and back to the patient through outlet tube 1114. Pump loop tube 1122 loads into red blood cell pump 1305, extracting red blood cells from centrifuge bowl 10 and driving them into cassette 1100 through inlet line 1108. Pump loop tubing 1123 is loaded into anticoagulant pump 1304, drives anticoagulant fluid into cassette 1100 through inlet tubing 1124, and drives anticoagulant fluid out of cassette 1100 through outlet tubing 1119 connected to inlet tubing 1106. The pump loop tubing 1124 is loaded into the recirculation pump 1303 and drives blood flow, e.g., plasma, from the cassette 1100 through the processing bag 50 and the radiation chamber 700.

When photopheresis treatment therapy in accordance with an embodiment of the method of the invention described below with reference to FIGS. 26-27 is required, each peristaltic pump 1301-1305 is activated. The peristaltic pumps 1301 + 1305 may be operated one at a time or in any combination. Pump 1301-. Holes 1137 and 1157 are strategically located on the substrate 1131 along the inner tubular line to facilitate proper routing. Through the use of pressure actuator 1240 and 1247, fluid may be routed along any path or combination thereof.

1. Filter assembly

The filter 1500 located within the cassette 1100 described above is shown in detail in fig. 6-10. Referring first to fig. 6 and 7, filter 1500 is shown fully assembled. Filter 1500 includes a filter housing 1501. Filter housing 1501 is preferably fabricated from a transparent or translucent medical grade plastic. However, the invention is not so limited and filter housing 1501 can be made of any material that does not contaminate blood or other fluids flowing therethrough.

Filter housing 1501 has four fluid connection ports extending therefrom, referred to as whole blood inlet 1502, whole blood outlet 1503, treated fluid inlet 1504, and treated fluid outlet 1505. Ports 1502 and 1505 are standard medical tubing connection ports that allow open communication of the medical tubing. Ports 1502-1505 include openings 1506, 1507, 1508, and 1509, respectively. Openings 1506, 1507, 1508 and 1509 extend through ports 1502, 1503, 1504 and 1505, forming fluid passageways into filter housing 1501 at desired locations.

Ports 1502, 1503, 1504, and 1505 are also used to secure filter 1500 in cassette 1100. At this point, the ports 1502, 1503, 1504, and 1505 can engage the U-shaped fasteners 1135 (fig. 3) of the cassette 1100. Filter housing 1501 also has a protrusion 1510 extending beyond the bottom surface of housing bottom 1518. The protrusion 1510 fits into a guide hole of the base 1131 of the cassette 1100 (fig. 3).

Referring now to fig. 8, a filter 1500 is shown in an exploded manner. The filter housing 1501 is a two-piece assembly including a roof 1511 and a base 1512. The top 1511 is attached to the base 1512 by any means known in the art, such as ultrasonic welding, heat welding, applying an adhesive, or by designing the top 1511 and base 1512 so as to result in a tight fit between the two components. Although the filter housing 1501 is shown as a two-piece assembly, the filter housing 1501 may be a single-piece structure or a multi-piece assembly.

The base 1512 has chamber dividing walls 1513 (FIG. 7) that project upwardly from the top surface of the housing bottom 1518. When the base 1512 and roof 1511 are combined, the top surface 1515 of the chamber separation wall 1513 contacts the bottom surface of the roof 1511, forming two chambers within the filter housing, a whole blood chamber 1516 and a filter chamber 1517. Fluid cannot pass directly between whole blood chamber 1516 and filter chamber 1517.

Whole blood chamber 1516 is a substantially L-shaped chamber having a floor 1514. Whole blood chamber 1516 has a whole blood inlet port 1519 and a whole blood outlet port (not shown) in floor 1514. Whole blood inlet port 1519 and whole blood outlet port are located at or near the end of substantially L-shaped whole blood chamber 1516. Whole blood inlet port 1519 forms a channel with opening 1506 of inlet port 1502 so that fluid can flow into whole blood chamber 1516. Also, a whole blood outlet port (not shown) forms a channel with opening 1507 of outlet 1503 so that fluid can flow out of whole blood chamber 1516.

Filter chamber 1517 has a bottom 1520. The floor 1520 has a raised ridge 1521 extending upwardly therefrom. The raised ridge 1521 is rectangular and forms a perimeter. Although the raised ridges 1521 are rectangular in the illustrated embodiment, the raised ridges 1521 can be a variety of shapes so long as they form a closed perimeter. The height of the raised ridge 1521 is less than the height of the chamber divider wall 1513. As such, when the roof 1511 and base 1512 are combined, a space is formed between the top of the raised ridge 1521 and the bottom surface of the roof 1511. A groove 1524 is formed between the raised ridge 1521 and the chamber dividing wall 1513.

To facilitate fluid flow through filter chamber 1517, bottom 1520 of filter chamber 1517 has an inlet 1522 for treated fluid and an outlet 1523 for treated fluid. An inlet hole 1522 for treated fluid is located outside the perimeter formed by raised ridge 1521 and forms a channel with opening 1508 of inlet 1504 so that fluid can flow from outside filter housing 1501 into filter chamber 1517. An outlet 1523 for the treated fluid is located inside the perimeter formed by the raised ridge 1521 and forms a channel with the opening 1509 of the outlet 1505 so that the fluid can flow out of the filter chamber 1517.

Filter 1500 also includes a filter element 1530. Filter element 1530 includes a frame 1531 having a filter media 1532 positioned therein. The frame 1531 has a neck 1534 forming a filter access hole 1533. Filter element 1530 is positioned in filter chamber 1517 such that frame 1531 fits into groove 1524 and neck 1534 surrounds treated blood inlet hole 1522. Filter access hole 1533 is aligned with access hole 1522 for processed fluid so that incoming fluid can flow freely through holes 1522 and 1533 into filter chamber 1517. Frame 1531 of filter element 1530 forms a sealed fit with raised ridge 1521. In order to exit filter chamber 1517 through treated fluid outlet hole 1523, all fluid entering filter chamber 1517 through holes 1522 and 1533 must pass through filter media 1532. Filter media 1532 preferably has a pore size of about 200 microns. Filter media 1532 may be formed of a woven mesh, such as woven polyester.

Filter chamber 1517 also includes a filter vent chamber 1540 in top 1511. Filter vent chamber 1540 has gas vent 1541 in the form of a hole (FIG. 9). Because gas vent 1541 opens into filter vent chamber 1540, and filter vent chamber 1540 opens into filter chamber 1517, gas accumulated within filter chamber 1517 can vent through gas vent 1541. Likewise, whole blood chamber 1516 includes a blood vent chamber 1542 located within roof 1511. Blood venting chamber 1541 has gas vent 1543 formed as a hole. Because gas outlet 1543 opens into whole blood vent chamber 1542, which in turn opens into whole blood chamber 1516, gas accumulated within whole blood chamber 1516 can vent through gas vent 1543.

FIG. 10 is a top view of filter 1500 having pressure sensors 1550 and 1551 connected to gas vents 1541 and 1543. Pressure sensors 1550 and 1551 are preferably pressure sensors (pressure sensors). Pressure sensor 1550 is connected to gas vent 1541 by vent tubing 1552. Vent tubing 1552 fits into gas vent 1541 to form a tight fit and seal. Since gas vent 1541 opens into filter vent chamber 1540, and filter vent chamber 1540 opens into filter chamber 1517, the pressure in vent tubing 1552 is the same as in filter chamber 1517. By sensing the pressure in vent line 1552, pressure sensor 1550 also senses the pressure within filter chamber 1517. Likewise, pressure sensor 1551 is connected to gas vent 1543 by vent tubing 1553. Vent tubing 1553 fits into gas vent 1543 to form a tight fit and seal, and pressure sensor 1551 detects the pressure in whole blood chamber 1516. When filter 1500 is positioned therein (fig. 2), filter vent chamber 1540 and blood vent chamber 1542 extend through openings 1132 and 1133 of cassette 1100. This allows the pressure within chambers 1516 and 1517 to be monitored while also protecting filter chamber 1500 and the fluid connected thereto.

Pressure sensors 1550 and 1551 are connected to controller 1554, which is a suitably programmed processor. The controller 1554 can be a main processor that drives the entire system or a separate processor connected to the main processor. Pressure sensors 1550 and 1551 generate electrical output signals that represent pressure readings within chambers 1517 and 1516, respectively. Controller 1554 receives basic data indicative of the pressure within chambers 1516 and 1517 at a frequency or continuously. Controller 1554 is programmed with values that indicate the desired pressures within chambers 1516 and 1517. Controller 1554 continuously analyzes the pressure data received from pressure sensors 1550 and 1551 to determine if the pressure readings are within a predetermined range of the desired pressure for chambers 1516 and 1517. Controller 1554 is also connected to whole blood pump 1301 and return pump 1302. In response to pressure data received from pressure sensors 1551 and 1550, controller 1554 may be programmed to control the speed of the whole blood pump 1301 and the return pump 1302, thereby adjusting the flow rate through pumps 1301 and 1302. The adjusted flow rates, in turn, adjust the pressures within whole blood chamber 1516 and filter chamber 1517, respectively. In this way, the pressure in the line that draws or returns blood from or to the patient is maintained at an acceptable level.

The function of filter 1500 during photopheresis treatment will be discussed with reference to FIGS. 1, 6 and 10. Although the function of filter 1500 will be described in detail with respect to withdrawing whole blood from a patient and returning components of the whole blood to the patient after processing thereof, the invention is not so limited. The filter 1500 can be in communication with virtually any fluid, including red blood cells, white blood cells, buffy coat, plasma, or combinations thereof.

Full blood pump 1601 draws whole blood from a patient connected to photopheresis kit 1000 through a needle connected to port 1193. The speed of the whole blood pump is set so that the line pressure at which whole blood is drawn from the patient is maintained at an acceptable level. After withdrawal from the patient, whole blood passes into the cassette 1100 through the inlet tube 1106. The inlet tube 1106 is fluidly connected to the inlet 1502 of the filter 1500. Whole blood passes through opening 1506 of inlet 1502 and into L-shaped whole blood chamber 1516. Whole blood enters chamber 1516 through access hole 1519 located on floor 1514. As more whole blood enters chamber 1516, it spills along floor 1514 until it reaches a whole blood outlet port (not shown) at the other end of L-shaped whole blood chamber 1516. As described above, the whole blood outlet is entirely in communication with the opening 1507 of the outlet 1503. Whole blood within chamber 1516 flows through floor 1514, through the whole blood outlet bore, into outlet 1503, and out of filter 1500 through opening 1507.

As the whole blood passes through the whole blood chamber 1516, gases entrained in the whole blood are vented. These gases collect in blood vent chamber 1542 and are then vented through gas vent 1543. Pressure sensor 1551 continuously monitors the pressure within blood chamber 1516 via vent tubing 1553 and transmits corresponding pressure data to controller 1554. Controller 1554 analyzes the received pressure data and adjusts the speed of whole blood pump 1301, and thus the flow rate and pressure within chamber 1516 and inlet tube 1106, as needed. Controller 1554 adjusts the pump speed to ensure that the pressure is within the desired pressure range.

The whole blood then exits filter 1500 through outlet 1503 and exits cassette 1100 through outlet tube 1115. The whole blood is then separated into components and/or processed as described in detail below. Such processed fluids (i.e., processed blood or blood components) must be filtered before being returned to the patient. Untreated fluids, such as red blood cells, must also be filtered and will be subjected to the following filtration process. The treated fluid flows into filter chamber 1517 through opening 1508 of inlet 1504. The inlet 1504 is fluidly connected to the pump loop pipe 1120. The treated fluid enters filter chamber 1517 through inlet hole 1522 and passes through filter inlet hole 1533 of filter element 1530. The treated fluid fills filter chamber 1517 until it overflows frame 1531 of filter element 1530, which is secured to raised ridge 1521. The treated fluid passes through filter media 1532. The filter media 1532 removes contaminants and other unwanted substances from the treated fluid while facilitating the release of entrained gases from the treated fluid. The treated fluid that passes through filter media 1532 collects on bottom 1520 of filter chamber 1517 within the perimeter formed by raised ridge 1521. The treated fluid then enters treated fluid exit 1523 and exits filter 1500 through opening 1506 of outlet 1502. The treated fluid is then returned to the patient through an outlet tube 1114 fluidly coupled to the outlet 1502. The treated fluid is driven through filter chamber 1517 and outlet tube 1114 by return pump 1302.

As the treated fluid flows through filter chamber 1517, gases entrained in the treated fluid are vented and collected in filter vent chamber 1540. These gases then exit filter 1500 through gas vent 1541. Pressure sensor 1550 continuously monitors the pressure within filter chamber 1517 via vent tube 1552 and transmits corresponding pressure data to controller 1554. Controller 1554 analyzes the received pressure data and compares it to the desired pressure value and range. Controller 1554 adjusts the speed of return pump 1302, and thus the flow rate and pressure within chamber 1517 and outlet tube 1114, as necessary.

B. Radiation cavity

FIGS. 11-16 show radiation chamber 700 of photopheresis kit 1000 in greater detail. Referring first to fig. 11, the radiation chamber 700 is formed by joining two plates, a front plate and a back plate, preferably about 0.06 inches to 0.2 inches thick, preferably formed of a material that is desirably transparent to wavelengths of electromagnetic radiation. In the case of ultraviolet a radiation, polycarbonate has been found to be most preferred, although other materials, such as acrylic, may be used. Also, many known connection methods may be used and need not be detailed here.

The first plate 702 has a first surface 712 and a second surface 714. In a preferred embodiment, first plate 702 has a first port 705 on first surface 712 in fluid communication with second surface 714. The second surface 714 of the first plate 702 has a raised border 726A that defines an enclosed space. The border 726A preferably extends substantially perpendicular (i.e., about 80-100 degrees) to the second surface 714. The raised partitions 720A extend (preferably substantially perpendicularly) from the second surface 714. Boundary 726A surrounds partitions 720A, with one end of each partition 720A protruding and contacting boundary 726A.

The second plate 701 has a first surface 711 and a second surface 713. In a preferred embodiment, second plate 701 preferably has second port 730 on second surface 711 in fluid communication with second surface 713. The second surface 713 of the backplate 701 has a raised boundary 726B that defines an enclosed space. The border 726B preferably extends substantially perpendicular (i.e., about 80-100 degrees) to the second surface 713. The rising partition (720B) extends from the second surface 713 (preferably substantially vertically). A border 726B surrounds partitions 720B, and one end of each partition 720A extends out and contacts the border (726B).

The joining of the second surfaces of the first and second plates results in a fluid-tight connection between boundaries 726A and 726B, thereby forming boundary 726. Spacers 720A and 720B are also joined to form a fluid tight connection, thereby forming spacer 720. The boundary 726 forms the radiation chamber 700 and, together with the partition 720, provides a path 710 with channels 715 for guiding a fluid. The path may be spiral, zigzag or wedge shaped. A spiral path is now preferred.

Referring to fig. 11 and 12, the radiation chamber 700 includes a convoluted path 710 for conveying a fluid, such as buffy coat or white blood cells, from an inlet 705 to an outlet 730 of the patient, i.e., the convoluted path 710 is in fluid communication with the inlet 705 of the front plate 702 and the outlet 730 of the back plate 701. Fluid from the patient is supplied from the cassette 1100 to the inlet 705 via the outlet conduit 1117. After being optically activated or following the convoluted path 710, the processed patient fluid is returned to the cassette 1100 through inlet tube 1112 (fig. 1 and 4). The patient fluid is driven by a recirculation pump 1303. The self-shielding effect of the cells is reduced when the cells are activated by the returning radiation light impinging back and forth on both sides of the radiation chamber 700.

Fig. 11 shows the pin 740 and groove 735 aligning the two plates of the radiant chamber prior to sealingly bonding the two plates together by RF welding, heat pulse welding, solvent welding, or adhesive bonding. More preferably, the joining of the plates is performed by adhesive joining and RF welding. The joining of the front and back plates is most preferably done using RF welding, since the design of the raised bulkhead 720 and perimeter 725 minimizes glare and even allows the use of RF energy. The positioning of the pin 740 and groove 735 may be inside the spiral path 710 or outside the spiral path 710. Fig. 2 also shows a diagram of the radiation cavity with axis L. A 180 degree rotation of the radiation chamber 700 about the axis L gives the original configuration of the radiation chamber. The radiation chamber of the invention has a C about an axis L₂And (4) symmetry.

Referring to fig. 11, 13 and 16, leukocyte enriched blood, plasma and infusion solution enter channel 715 through an inlet 705 of front plate 702 of radiation chamber 700. In order to expose the leukocyte-rich blood to radiation at a large surface area and reduce the self-shielding effect created by the lower surface area/volume ratio, the channel of the radiation chamber 700 is relatively "thin" (e.g., approximately 0.04 "from the distance between the two plates). The cross-sectional shape of the channel 715 is substantially rectangular (e.g., rectangular, rhomboidal, or trapezoidal), with the distance between the baffles 720 as their long sides and the distance between the plates as their short sides. The shape of the cross-section is designed to optimize irradiation of cells passing through the channel 715. While a serpentine path 710 is preferred to avoid or reduce stagnant areas of flow, other arrangements are contemplated.

The radiation chamber 700 is effective to activate the photoactivatable agent by radiation from the photoarray assembly, e.g., an assemblyFor activation (758) (fig. 16). For use in an arrangement where the edge 706 is oriented downwards and the edge 707 is directed upwards, a radiation plate and UVA light assembly (759) is designed. In this orientation, fluid entering inlet 705 is able to drain from outlet 730 under the force of gravity. In the most preferred embodiment, irradiation of both sides of the irradiation chamber occurs simultaneously, while still allowing flexible movement of the chamber. UVA light assembly 759 is positioned within UV chamber 750 of durable tower system 2000 (fig. 17 and 18).

The fluid path of the radiation chamber is looped to form two or more channels in which leukocyte enriched blood circulates when activated by UVA light. Preferably, the radiation chamber 700 has 4 to 12 channels. More preferably, the radiation chamber has 6 to 8 channels. Most preferably, the radiation chamber has 8 channels.

Figure 14 shows a cross-sectional view of the radiation chamber. The channel 715 of convoluted path 710 is formed by the junction of raised baffle 720 and the perimeter 726 of the plate.

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

A method of irradiating cells using the radiation chamber 700 when treating cells in vitro using electromagnetic radiation (UVA) for treating a patient, such as inducing apoptosis and injecting cells into a patient, will now be discussed. The treated cells are preferably leukocytes.

In one embodiment of the method, the photoactivatable or photosensitive compound is first applied to at least a portion of the blood of the subject prior to treating the cells in vitro. The photoactivatable or photosensitive compound may be administered in vivo (e.g., orally or intravenously). When administered in vivo, the photosensitive compound may be administered orally, intravenously and/or by other conventional routes of administration. The oral dosage of the photosensitive compound may range from about 0.3 to about 0.7mg/kg, more particularly about 0.6 mg/kg.

When administered orally, the photoactive compound may be administered at least about one hour prior to the photopheresis treatment and the time of administration is no more than three hours prior to the photopheresis treatment. If administered intravenously, the time will be shorter. Alternatively, the photosensitive compound may be administered prior to or simultaneously with exposure to ultraviolet light. The light-sensitive compound may be added to whole blood or a portion thereof so long as the target blood cells or blood components receive the light-sensitive compound. A portion of the blood may first be treated using known methods to substantially remove red blood cells, and then a photoactivatable compound may be added to the resulting leukocyte-rich fraction. In one embodiment, the blood cells comprise leukocytes, particularly T cells.

In some psoralen cases, photoactivatable or photosensitive compounds can bind to nucleic acids upon activation by electromagnetic radiation exposed to a specified spectral line, e.g., ultraviolet light.

Photoactivatable compounds may include, but are not limited to, compounds known as psoralens (or furocoumarins) and psoralen derivatives, such as those described in U.S. patent No.4,321,919 and U.S. patent No.5,399,719. Photoactivatable or photosensitive compounds that may 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-methoxypsoralen; 4-methylpsoralen; 4, 4-dimethylpsoralen; 4-5' -dimethylpsoralen; 4 '-aminomethyl-4, 5', 8-trimethylpsoralen; 4 '-hydroxymethyl-4, 5', 8-trimethylpsoralen; 4', 8-methoxypsoralen; and 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, photosensitive compounds that may be used include psoralen derivatives, amotosalen (S-59) (Cerus, corp., Concord, CA). See, e.g., U.S. patent nos.6,552,286; 6,469,052, respectively; and 6,420,570. In another embodiment, the photosensitive compound that may be used in accordance with the present invention comprises 8-methoxypsoralen.

8-methoxypsoralen (Methoxsalen) is a naturally occurring photoactivated substance found in seeds of Ammi maju (an umbrella plant). It belongs to a compound known as psoralen or furocoumarin. The chemical name is 9-methoxy-7H-furan [3, 2-g][1]-benzopyran 7-one. The formulation of the drug is a sterile liquid at a concentration of 20mcg/mL in a 10mL vial. See http:// www.therakos.com/TherakosUS/pdf/uvadexpi. In vitro photoseparation displacement and varying doses in beagle dogsAnd toxicology studies of ultraviolet light in research manuals.

Next, a portion of the patient's blood, subject's blood, or donor's blood to which the photoactivatable compound has been added is treated by photopheresis using ultraviolet light. The photopheresis treatment may be performed using long wavelength Ultraviolet (UVA) light in a wavelength range of 320 to 400 nm. However, this range is not limiting and is provided as an example only. Exposure to UV light during the photopheresis treatment is long enough to deliver, for example, about 1-2J/cm²To the blood.

The photopheresis step is accomplished extracorporeally by installing radiation chamber 700 in photoactivation chamber 750 (FIGS. 17 and 18) of durable tower system 2000. In one embodiment, when the photopheresis step is performed ex vivo, at least a portion of the treated blood is returned to the patient, recipient or donor. The treated blood or treated concentrated leukocyte fraction (as the case may be) can then be returned to the patient, recipient or donor.

The photopheresis procedure consists of three stages, including 1) collection of the buffy coat fraction (concentrated white blood cells), 2) irradiation of the collected buffy coat fraction, and 3) reinfusion of the treated white blood cells. This process will be discussed in more detail below. Typically, whole blood is centrifuged and separated in the centrifuge bowl 10. A total of about 240ml of buffy coat and 300ml of plasma were separated and stored for UVA irradiation.

Collected plasma and buffy coat with heparinized standard saline and heparinized standard saline(8-methoxypsoralen soluble in water) were mixed together. The mixture flowed through the radiation chamber of the present invention into a 1.4mm thick layer. Radiation cavity 700 insertionIn light activation chamber 750 of tower system 2000 between two clusters of UVA lamps (fig. 15).The UVA lamps radiate both sides of the radiation chamber 700 which is transparent to UVA. Thereby generating 1-2J/cm per unit lymphocyte by exposure to ultraviolet A light²Average exposure amount of (c). After the photoactivation period, the cells are removed from the radiation chamber 700.

In a preferred embodiment of the invention, the cells are removed by gravity and any cells retained in the chamber are displaced from the chamber by an additive fluid selected from the group consisting of saline, plasma and combinations thereof. For small patients, such as children (e.g. below 30 kg) or patients whose vascular system is susceptible to fluid overload, the added fluid volume for the radiation lumen will preferably not exceed 2 times the lumen volume, preferably not exceed 1 time the lumen volume, more preferably not exceed 0.5 and 0.25 times the lumen volume. The treated cell volume is reinfused into the patient.

For a description of the same photopheresis system and method, see U.S. patent application No.09/480,893, which is specifically incorporated herein by reference. Also useful herein are those described in U.S. patent nos.5,951,509; 5,985,914, respectively; 5,984,887, respectively; 4,464,166, respectively; 4,428,744, respectively; 4,398,906, respectively; 4,321,919, respectively; the methods and systems described in PCT publication Nos. WO97/36634 and WO97/36581, all of which are expressly incorporated herein by reference.

An effective amount of light energy delivered to a biological fluid can be detected using the method and system described in U.S. patent No.6,218,584, which is specifically incorporated herein by reference. Indeed, the application of ECP to the various diseases described herein may require that the light energy dose be sized to optimize the treatment process.

In addition, the photosensitizing agent used in the ECP process may be removed prior to returning the treated biological fluid to the patient. For example, 8-methoxypsoralen (A) is used in ECP process). 8-methoxypsoralen belongs to a group of compounds in the psoralen class. Exposure to 8-methoxypsoralen or other psoralens can result in undesirable effects on the patient, recipient or donor, such as phototoxicity or other toxic effects associated with psoralens and their degradation products. Thus, psoralens, psoralen derivatives, or psoralen degradants remaining in the biological fluid may be removed after UV exposure. The process of removing psoralen biofluids is described in U.S. patent No.6,228,995, which is specifically incorporated herein by reference.

C. Centrifugal rotating drum

In particular embodiments, the present invention relates to methods and apparatus for separating fluid components, such as biological fluid components by density or weight. Biological fluids include fluids that are composed, present, or used in, or delivered to, living organisms. Indeed, biological fluids may include body fluids and their components, such as blood cells, plasma, and other fluids that include biological components, including living organisms, such as bacteria, cells, or other cellular components. The biological fluid may also include whole blood or particular whole blood components, including red blood cells, platelets, white blood cells, and precursor cells. In particular, it is desirable to remove blood from a patient for therapeutic purposes, such as extracorporeal treatment. It should be understood, however, that the present invention is suitable for use with a variety of centrifugal processing devices, and that specific examples are given herein for illustrative purposes only. Other uses of separation techniques and devices may include other medical treatments such as dialysis, chemotherapy, separation and removal of platelets, and separation and removal of other specific cells. In addition, the present invention may be used to separate other types of fluids, including various non-medical applications, such as separation of oil and fluid components. All of the ingredients used in the present invention should not adversely affect the biological fluid or render them unsuitable for their intended purpose of use, such as those described herein, and may be made of any suitable material compatible with the purpose of use described herein, including but not limited to plastics such as polycarbonate, methyl methacrylate, styrene-acrylonitrile, acrylic, styrene, acrylonitrile, or any other plastic. Any parts of the present invention that are shown joined together and forming a fluid tight seal in the present invention may be joined using any suitable conventional method, including, but not limited to, adhesive, ultrasonic welding, or RF welding.

The present invention has several advantages over centrifuges using conventional Latham bowl. In thatXTS^TMThe Latham bowl in the system has an inlet that allows whole blood to enter the bowl and an outlet that allows plasma and buffy coat to exit. Having only two ports limits the amount of buffy coat that can be collected in each cycle. Each cycle includes filling the bowl with whole blood; 2) rotating the bowl to separate the whole blood into plasma, buffy coat, and red blood cells; 3) collecting the buffy coat for processing, 4) stopping the bowl; and 5) returning the collected plasma and red blood cells. The buffy coat collection method is characterized as "batch-wise" in that the amount of buffy coat required for radiation treatment can be collected only after a few cycles of buffy coat collection. The limited volume of buffy coat collected per cycle is due to the retention of accumulated red blood cells inside the bowl. Thus, the ability to empty the accumulated red blood cells only after the buffy coat collection cycle is complete is an inherent limitation of the Latham bowl.

The bowl of the present invention has three separate fluid conduits that serve as one inlet and two outlets. The additional fluid conduit achieves 1) reduced patient treatment time by continuously spinning throughout the buffy coat collection process without stopping the rotation to remove accumulated red blood cells; 2) treating patients with small blood volume; by continuously returning collected red blood cells to the patient, these patients may be more amenable to medical treatments requiring the buffy coat or components thereof, such as extracorporeal photopheresis; 3) due to the increased rotation or spinning time, the different components of the cellular fraction within the buffy coat can be better separated and 4) the high density red blood cell fraction can be separated from the whole blood. The centrifuge bowl also provides the opportunity to reduce the treatment time for any medical procedure used to collect the buffy coat fraction from a patient, which fraction is substantially free of red blood cells, such as extracorporeal photopheresis replacement.

For the purposes of achieving the objectives in accordance with the present invention, as embodied and broadly described herein, FIGS. 35 and 36 illustrate a particular embodiment of the present invention. The embodiment shown in fig. 35 includes a centrifuge bowl 10A, a conduit assembly 860A, a frame 910A, and a stationary actuator 918A. The centrifuge bowl 10A is in fluid communication with the external conduit 20A of the conduit assembly 860A. Lower sleeve end 832A (FIG. 46) of coupling sleeve 500A is secured to bowl 10A. Upper sleeve end 831A of adapter sleeve 500A is secured to external conduit 20A, connects external conduit 20A to bowl 10A, and provides fluid communication from external conduit 20A to bowl 10A. This fluid communication allows fluid 800 to be provided to bowl 10A through external conduit 20A. This fluid communication also allows the separated fluid components 810 and 820 to be removed from the bowl 10A through the external conduit 20A. The drum 10A and frame 910A are adapted to rotate about a central axis 11A.

Referring to FIG. 36, bowl 10A includes housing 100A, coupling sleeve 500A, top core 200A, bottom core 201A, and housing bottom 180A. The housing 100A may be constructed of any suitable biocompatible material as previously described and for the purpose shown in FIG. 36 is constructed of a transparent plastic so that the cores 200A and 201A are visible therethrough. Housing 100A is connected to housing bottom 180A, which in turn includes protrusions 150A for locking bowl 10A in a rotating device such as rotating device 900A. The bowl 10A is preferably of simplified construction and is easily manufactured by molding or other known manufacturing processes so that it may be disposable or used for a limited number of treatments, and most preferably is capable of containing about 125ml of fluid, which may be pressurized. In alternative embodiments, the volume of the bowl may vary depending on the health of the patient and the amount of extracorporeal volume he or she allows. The capacity of the bowl may also vary depending on the use of the bowl or the particular treatment for which the bowl is used. In addition, to avoid contamination of the biological fluid, to avoid exposure of personnel engaged in the treatment operation to the fluid, the transfer operation is preferably carried out in a sealed flow system, which may be pressurized, preferably formed of a flexible plastic or similar material that can be discarded after each use.

As shown in fig. 36 and 37, the housing 100A is substantially conical with an upper housing end 110A, an outer housing wall 120A, and a lower housing end 190A. The housing 100A may be made of plastic (such as those listed above) or any other suitable material. The upper housing end 110A has an outer surface 110B, an inner surface 110C and a housing outlet 700A providing a passageway between the surfaces. The upper housing also preferably has a neck 115A formed adjacent the housing outlet 700A. The housing outlet 700A and neck 115A are sized to allow passage of the body 830A of the connection sleeve 500A when retaining the sleeve flange 790A, which extends from the body 830A of the connection sleeve 500A. In one embodiment of the invention, an annular ring 791A may be interposed between the sleeve flange 790A and the inner surface 110C of the housing end 110A to ensure that a fluid tight seal is provided. In an alternative embodiment of the invention shown in FIG. 53, a second sleeve flange 790B extends from the body 830A of the coupling sleeve 500B distal from the sleeve flange 790A. Both sleeve flanges 790A and 790B are adapted to fit within neck 115A, and retain an annular ring 791A therebetween. In this embodiment, a fluid tight seal is provided by the o-ring contacting the body 830A and the inner surface 110C of the housing end 110A adjacent the neck 115A. However, coupling sleeve 500A may be secured to bowl 10A by any means including, for example, a lip, groove, or close fit and adhesion with components of bowl 10A. The housing wall connects the upper housing end 110A and the lower housing end 190A. Lower housing end 190A is connected to housing bottom 180A and has a larger diameter than upper end 110A. The housing floor 180A mates with the lower housing end 190A and serves to provide a fluid tight seal there. Lower housing end 190A may be secured to housing floor 180A using any conventional method, including but not limited to, adhesive, ultrasonic welding, or RF welding. The housing bottom 180A may have a notch 185A for collecting dense fluid 810. The diameter of the outer housing 100A increases from the upper housing end 110A to the lower housing end 190A.

The housing 100A is adapted to be rotatably coupled to a rotating device 900 (FIG. 35), such as a rotor drive system or turret 910. For example, the rotatable connection may be a bearing that allows the bowl 10A to rotate freely. The housing 100A preferably has a locking mechanism. The locking mechanism may be one or more protrusions 150A designed to interact with indentations in the corresponding centrifugation container, or any other suitable interconnection or locking mechanism or equivalent as disclosed in the prior art. The locking mechanism may also include a keyway 160 (fig. 51).

Referring to fig. 37, the housing 100A and the base 180A define an interior space 710A in which the cores 200A and 201A will mate when the bowl 10A is assembled. When fully assembled, the cores 200A and 201A are all within the interior space 710A of the housing 100A, occupying the coaxial space of the interior space 710A around the axis 11A.

Referring to fig. 38, 40 and 44, the top core 200A and the bottom core 201A are substantially conical and have upper core ends 205A, 206A, respectively; outer core walls 210A, 211A; and lower core ends 295A, 296A. The cores 200A, 201A occupy a coaxial space of the interior space 710A of the bowl 10A, and a separation space 220A is formed between the upper end 205A and outer wall 210A of the top core 200A, and the outer wall 211A and lower core end 296A of the bottom core 201A, and the housing 100A. The separate space 220A is a space of the internal space 710A between the cores 200A and 201A and the casing 100A.

As shown in fig. 40 and 41, the top core 200A includes an upper core end 205A and a lower core end 295A connected by an outer core wall 210A. The outer core wall 210A has an outer surface 210B and an inner wall surface 210C and a lower edge 210D. The diameter of the top core 200A preferably increases from the upper core end 205A to the lower core end 295A. Upper core end 205A also includes an outer surface 205B and an inner surface 205C. Centrally located about the central axis and extending perpendicularly from the upper surface 205B is a lumen connector 481A. Cavity connector 481A has a top surface 482A and a wall surface 482B. The top surface 482A has two channels 303B and 325D that provide fluid communication with the second bowl channel 410A and the first bowl channel 420A, respectively, through the upper core end 205A. Second bowl channel 410A is a conduit having a conduit wall 325A extending perpendicularly from an inner surface 481C of lumen connector 481A.

39B, 39A and 40, second bowl channel 410 is in fluid communication with conduit channel 760A through conduit 321A, which conduit 321A has a first end 321B and a second end 321C that fits within channel 325D of chamber connector 481A. In operation, conduit channel 760A of external conduit 20A is in fluid communication with bowl channel 410A. The first bowl channel 420A is a second conduit having a channel wall 401A extending substantially perpendicularly from an inner surface 481C of the lumen connector 481A. 39A, 39B and 40, first bowl channel 420A is in fluid communication with conduit channel 780A of outer conduit 20A through hollow cylinder 322A having first end 322B and second end 322C that engage opening 303B of top surface 482A. As shown in one embodiment of the present invention, second bowl channel 410A is disposed within first bowl channel 420A. In an alternative embodiment of the invention shown in FIG. 53, duct wall 325A can be comprised of an upper component 325F and a lower component 325G and be fused integrally with duct walls 401A and 402A.

The top surface 482A also has a notch 483A that provides fluid communication with the chamber 740A. When assembled, lumen 740A is defined by the lumen of mounting recess 851A, which has a volume less than the volume occupied by hollow cylinders 321A and 322A in the case of connection between connection sleeve 500A and lumen connector 481A. The chamber 740A is in fluid communication with the conduit channel 770A and with the separation space 220A adjacent the neck 115A via indentation 483A. Such that indentation 483A forms a passageway for removal of the second separated fluid component 820 through the bowl chamber 740A. Optionally, a plurality of spacers 207A are provided on the outer surface 205B and extend from the outer surface and contact the inner surface 110C of the upper housing end 110A to ensure fluid communication between the separation space 220A and the passage formed by the indentation 483A.

In an alternative embodiment shown in FIGS. 53, 54, and 55, conduits 321A and 322A may be affixed to openings 325D and 303B in top surface 482A of lumen connector 481A. In addition, indentation 483A may form a number of channels in lumen connector 481A and, when connected to connection sleeve 500A or 500B, form lumen 740B. The cavity 740B suitably has one or more surfaces 742A that can mate with the male end 853A of the connection sleeve 500A (the male end 853A surrounds the end 861 of the outer conduit 20A). To facilitate accurate orientation of coupling sleeve 500A to lumen connector 481A, the shape of male end 853A and lumen 740B may be asymmetrical, or as shown in FIGS. 53, 54 and 55, a guide 855A may be provided that extends from the top surface of lumen connector 481A and that fits within opening 857A of sleeve flange 790A.

Referring back to fig. 40, lower core end 295A includes an upper plate 299A having a top surface 298A, a bottom surface 297A and an edge 299B that is attached to and in direct contact with lower edge 210D of outer core wall 210A. The edge 299B of the upper plate 299A is adapted to be coupled to and form a fluid tight seal with the lower edge 210D of the outer core wall 210A. Extending perpendicularly from top surface 298A of upper plate 299A is a channel wall 402A having an upper end 402B and a lower end 402C and surrounding an opening 303A substantially in the center of upper plate 299A. A plurality of fins 403A attached to the outer surface of channel wall 402A and top surface 298A support chamber wall 402A. Channel wall 402A is adapted to mate with channel wall 401A forming a fluid seal and providing chamber 400A. First bowl channel 420A is in fluid communication with conduit channel 780A of outer conduit 20A via conduit 322A. As will be discussed, opening 303A places chamber 400A in fluid communication with compartment 220A. The first bowl channel 420A also surrounds the second bowl channel 410A.

Referring to fig. 43A, 43B and 44, the bottom core 201A includes an upper core end 206A, an outer core wall 211A and a lower core end 296A. The outer core wall 211A has an outer surface 211B, an inner wall 211C, and a lower edge 211D. The diameter of the bottom core 201A preferably increases from the upper core end 206A to the lower core end 296A. Bottom core 201A also has a top surface 309A and a bottom surface 309B. The top surface 309A has a notch 186A (preferably substantially circular) substantially in the center of the surface 309A of the upper core end 206A. Notch 186A has an upper surface 186B and an inner surface 186C. The notch 186A has an opening 324D in the upper surface 186B that extends to the inner surface 186C. In an alternative embodiment of the invention shown in FIG. 53, the upper surface 186B may also have a groove 186D adapted to receive an annular ring and form a fluid seal around the lower end 325B of the conduit wall 325A. Projecting perpendicularly from inner surface 186C around opening 324D is conduit wall 324A having a distal end 324B. Extending from the notch 186A to the outer surface 211B of the outer core wall 211A on the top surface 309A are one or more channels 305A. Top surface 309A may be horizontal or slope upward or downward from notch 186A. If top surface 309A slopes upward or downward from notch 186A to core end 206A, one of ordinary skill in the art would be able to adjust the shape of upper plate 299A and upper core end 295A accordingly. The channel 305A may have the same depth throughout the length of the channel 305A. However, the channel 305A may be inclined radially downward or upward from the center. As will be appreciated by those of ordinary skill in the art, if the top surface 309A is sloped upward or downward and the channel 305A has a constant depth, then the channel 305A slopes upward or downward accordingly.

Referring to fig. 38, when assembled, bottom surface 297A of upper plate 299A is in direct contact with top surface area 309A of bottom core 201A. This contact forms a fluid seal between the two surface areas, forming an opening 305B from the gap 186A to the channel 305A. A second opening 305C from the channel 305A is formed in the outer surface 211B of the outer core wall 211A. Opening 305B provides fluid communication from notch 186A through channel 305A and opening 305C to compartment 220A (fig. 38 and 40). So that fluid 800 flows through conduit channel 780A and then through first bowl channel 420A. Fluid 800 then flows from first bowl channel 420A to separation space 220A through channel 305A.

Referring to fig. 43A and 44, lower core end 296A has a lower plate 300A with a top surface 300B, a bottom surface 300C and an outer edge 300D. Extending from the bottom surface 300C of the lower plate 300 are one or more protrusions 301A. The outer edge 300D is connected to and forms a fluid seal with the lower edge 211D of the outer core wall 211A. Lower plate 300A, which is positioned above shell bottom 180A, is circular and curves radially upward from its center (shown in fig. 44). Alternatively, the lower plate 300A may be flat. As shown in fig. 38, when positioned above housing bottom 180A, there is a space 220C between lower plate 300A and housing bottom 180A. The space 220C is in fluid communication with the separation space 220A. The lower plate 300A may be made of plastic or any other suitable material. Also extending substantially perpendicularly from the lower surface 300C of the lower plate 300A is a conduit 320A. Conduit 320A has a first end 320B that extends into space 220C between lower plate 300A and housing floor 180A and a second end 320C that extends above top surface 300B of lower plate 300A. The diameter of the conduit 320A mates with the conduit wall end 324B. The space inside conduit walls 324A and 325A includes chamber 400B. In addition to the second drum channel 410A, the space defined by the lower plate 300A, the inner surface 211C, and the ceiling 253A of the bottom core 201A may include air or solid material (see fig. 43B and 44).

In an alternative embodiment of the invention shown in fig. 53, support walls 405A and 407A may optionally be present. Support wall 405A extends perpendicularly from bottom surface 309B. Support wall 407A extends perpendicularly from top surface 300B of lower plate 300A and is connected to support wall 405A when bottom core 201A is assembled. Conduit wall 324A may be connected to conduit 320A to form a fluid seal, and conduits 324A, 320A may merge with support walls 405A and 407A, respectively. In addition, there are one or more orientation spacers 409A extending from the bottom surface 300C of the lower plate 300A that fit within the notch 185A.

One of ordinary skill in the art will readily recognize that the bowl 10A will need to be balanced about the central axis 11A. Thus, a weight that facilitates maintaining the balance of the bowl 10A, such as weight 408A shown in FIG. 53, may be added as part of the apparatus

Referring to FIG. 38, bowl 10A is configured such that housing 100A, cores 200A and 201A, lower plate 300A and upper plate 299A, housing floor 180A, external conduit 20A and connecting sleeve 500A, and chambers 400A and 400B are connected and rotate together. The housing bottom 180A of the outer housing 100A includes recesses 181A on its top surface that are shaped to fit the protrusions 301A of the lower plate 300A. As shown, lower plate 300A has a rounded protrusion 301A on its bottom surface 300C to limit movement of lower plate 300A relative to housing bottom 180A. When assembled, the individual protrusions 301A on the bottom surface of lower plate 300A form a tight fit with recesses 181A on housing bottom 180A. Thus, when housing 100A is rotated, outer conduit 20A and coupling sleeve 500A, top core 200A, upper plate 299A, bottom core 201A, lower plate 300A, housing floor 180A, and chambers 400A and 400B will rotate therewith.

As shown in FIG. 38, chamber 400A allows whole blood 800 to enter the bowl 10A through the first bowl channel 420A. First bowl channel 420A provides a passageway for fluid 800 to flow through chamber 400A into gap 186A and then through channel 305A into compartment 220A. The cavity 400A is positioned within the top core 200A. Chamber 400A has a height from upper chamber end 480A to lower chamber end 402C. Lumen 400A is formed by the connection of channel wall 401A extending from inner surface 481C of lumen connector 481A and channel wall 402A extending from top surface 298A of upper plate 299A. Channel wall 401A is supported by a plurality of fins 251A that are connected to inner wall surface 210C of outer core wall 210A and inner surface 205C of upper core end 205A, and channel wall 402A is supported by a plurality of fins 403A (fig. 40). It is readily apparent that the height of the cavity 400A can be adjusted by varying the size and shape of the core 200A, channel wall 401A, channel wall 402A, conduit wall 325A, and varying the height of the conduit wall 324A.

As shown in fig. 38, chamber 400A, from upper chamber end 480A to lower chamber end 402C, contains an inner chamber 400B. Lower chamber end 402C has an opening 303A in fluid communication with compartment 220A through a number of channels 305A. In the illustrated embodiment, the chamber 400A includes a first bowl channel 420A. The second drum channel 410A is located inside the first drum channel 420A of the top core 200A and is contained therein from the chamber end 480A to the chamber 402C. In addition, second bowl channel 410A forms a channel from lower plate 300A below through chamber 400B for removal of first separated fluid component 810 collected in gap 185A of housing bottom 180A. Second bowl channel 410A extends from bottom 180A of housing 100A through chamber 400B and to conduit channel 760A of external conduit 20A.

Referring to fig. 38 (conduit 321C not shown), the lumen 400B allows red blood cells 810 to exit the bowl 10A through the second bowl channel 410A, which provides fluid communication from the bottom of the shell over the gap 185A to the opening 324E. The inner chamber 400B has an upper duct end 325C and a lower duct end 324B and includes two duct walls 324A and 325A connected in a fluid-tight manner and forming a second bowl channel 410A having a smaller diameter than the first bowl channel 420A and being spaced apart and separated therefrom. Duct wall 325A is supported by fins 251A that extend through duct wall 401A and connect to duct wall 325A. Unlike chamber 400A, which has one end adjacent notch 186A, chamber 400B extends beyond notch 186A and through bottom plate 300A. The first conduit wall 325A has an upper end 325C with an opening 325D at the top surface 482A of the cavity connector 481A, and a lower end 325B with an opening 325E that mates with the upper end 324C of the conduit wall 324A. An upper end 324C of conduit wall 324A is higher than notch 186A and has an opening 324D. Duct wall 324A also has a lower end 324B and is supported by a number of vanes 252A. The lower end 324B having the opening 325E is connected to the duct 320A having the opening 302A positioned near the center of the lower plate 300A. The connection of openings 325E and 302A provides fluid communication between chamber 400B and space 220C between lower plate 300A and housing bottom 180A. Space 220C between lower plate 300A and housing floor 180A is in turn in fluid communication with separation space 220A.

The conduit 320A provides a close fit with the lower end 324B, providing support for the second bowl channel 410A. Each bowl channel 420A and 410A may be made of any type of flexible or rigid tubing (e.g., medical tubing), or other device that provides a sealed passageway for a pressurized or non-pressurized fluid stream, and is preferably disposable and sterilizable, i.e., manufactured by a simple and efficient manufacturing process.

1. Driving tube

As shown in fig. 39A and 39B, conduit assembly 860A is coupled to bowl 10A by a coupling sleeve 500A that is coupled to a first end 861A of outer conduit 20A having a first conduit passage 780A, a second conduit passage 760A and a third conduit passage 770A. Each conduit passage is in fluid communication with first bowl passage 420A, second bowl passage 410A, and bowl chamber 740A. The three conduit channels are spaced at 120 ° intervals at the same interval in the outer conduit 20A and are of the same diameter (see fig. 50). When fluidly connected to external conduit 20A and bowl 10A, conduit channel 780A is fluidly connected to first bowl channel 420A in order to flow fluid 800 from external conduit 20A into bowl 10A for separation. Similarly, second conduit channel 760A is fluidly connected to second bowl channel 410A for flowing first separated fluid component 810 from bowl 10A into external conduit 20A. Finally, third conduit channel 770A is connected to bowl chamber 740A for removing second separated fluid component 820 from bowl 10A.

As shown in FIG. 45, outer conduit 20A has a connection sleeve 500A on a first end 861A of outer conduit 20A and a retaining sleeve 870A on a second end 862A of outer conduit 20A. Optionally, there is a first shoulder 882 and a second shoulder 884 extending perpendicularly from the outer conduit 20A between the connection sleeve 500A and the anchor sleeve 870A on the outer conduit 20A and having a larger diameter. Between the connection of sleeve 500A and anchor sleeve 870A (or first and second shoulders 882, 8 if present)84, between them) are first and second bearing rings 871A and 872A. To use this type of tube in a centrifuge, the outer conduit 20A, anchor sleeve 870A and connecting sleeve may be made of the same or different biocompatible materials of suitable strength and flexibility (one such preferred material is). The connection sleeve 500A and the anchor sleeve 870A may be connected by any suitable means, such as adhesive, welding, and the like. However, the preferred manner for ease of manufacture is to over mold (overmold) connection sleeve 500A and anchor sleeve 870A to outer conduit 20A.

Referring to fig. 45, 48 and 49, anchor sleeve 870A includes a body 877B having a first anchor end 873A and a second anchor end 874A. Anchor sleeve 870A is attached to second conduit end 862A of outer conduit 20A (preferably by over-molding) and increases in diameter from first loop 873A to loop 874A. Spaced distally from second end 874A is a collar 886A extending perpendicularly from body 877B and having a larger diameter than body 877B of anchor sleeve 870A. A number of ribs 877A having a first rib end 877B between the collar 886A and the second anchor end 873A and a second rib end 877C extending beyond the first anchor end 873A are attached to the body 877B. The second rib end 877C is connected with a ring 880A, which is also connected to the outer conduit 20A. The ribs 877A are parallel to the outer conduit 20A and are preferably located on the extent of the conduit channels 760A, 770A and 780A that are closest to the surface of the outer conduit 20A (FIG. 50). If not reinforced, the areas of the conduit channels 760A, 770A and 780A closest to the outer diameter of the outer conduit 20A are prone to damage during high speed rotation. Having the ribs parallel the conduit passage beyond the fixed sleeve end 873A provides reinforcement to this area and prevents damage to the conduit during high speed rotation. In one aspect, the ribs prevent bending of the outer conduit 20A in this region and act as structural elements to transfer torsional stresses to the retaining sleeve 870A.

The connection sleeve 500A includes a body 830A having an upper sleeve end 831A and a lower sleeve end 832A (fig. 46 and 47). Lower sleeve end 832A has a sleeve flange 790A and a number of projections 843A that are sized to engage indentations 484A on wall surface 482A of lumen connector 481A. When the bowl 10A is assembled, a fluid seal may be provided by positioning the o-ring 791A around the body 830A and pressing the o-ring 791A between the flange 790A and the housing 100A. Upper sleeve end 831A is secured to external conduit 20A, and with reference to FIGS. 46, 39A and 39B, coupling sleeve 500A is secured to bowl 10A by means of sleeve flange 790A and fluidly couples conduit channels 780A, 760A, 770A of external conduit 20A to bowl channels 420A and 410A of bowl 10A, and chamber 740A. When assembled, connection sleeve 500A is mounted to lumen connector 481A (FIGS. 39A and 39B).

Connection sleeve 500A preferably increases in diameter from upper sleeve end 831A to lower sleeve end 832A and is overmolded onto first conduit end 861A of outer conduit 20A. Coupling sleeve 500A connects bowl 10A to external conduit 20A without the use of a rotating seal, which is generally positioned between bowl 10A and coupling sleeve 500A. As explained above, or alternatively by using, for example, an o-ring, groove, or lip, a grommet-type connection, welding, or a tight fit with or without adhesive in either bowl 10A or coupling sleeve 500A, a less-hermetic connection between bowl 10A and coupling sleeve 500A may be created.

As shown in FIGS. 46 and 39B, sleeve flange 790A has a bottom surface 847A that forms a tight seal with top surface 482A of lumen connector 481A. However, chamber connector 481A has a number of indentations 483A that provide fluid communication between separation chamber 220A and bowl chamber 740A, which in turn is in fluid communication with conduit channel 770A. Bowl chamber 740A is defined by chamber mounting recess 851A and top surface 482A of chamber connector 481A, except for the space occupied by hollow cylinders 321A and 322A. A plurality of protrusions 843A on the bottom surface 847A of sleeve flange 790A engage and slide into indentations 484A on the wall surface 482B of lumen connector 481A to provide a tight fit.

Coupling sleeve 500A helps secure external conduit 20A to bowl 10A, thereby fluidly coupling external conduit 20A to bowl 10A. The fluid connection enables fluid 800 to be provided to bowl 10A through external conduit 20A. Likewise, the fluid connection may also allow the separated fluid component b, 820 to be removed from the bowl 10A through the external conduit 20A.

The outer tube 20A has a substantially constant diameter that helps reduce stiffness. The very hard outer tube 20A will heat up and break down very quickly. In addition, constant diameter tubing is inexpensive/easy to manufacture, easy to connect test with the adapter sleeve 500A and the retaining sleeve 870 size, and allows the bearing rings 871A, 872A to slide over them easily. Preferably, the movement of the bearings 871A and 872A will be limited by the first and second shoulders 882A and 884A. The outer conduit 20A may be made of any type of flexible tubing, such as medical tubing, or any such device that provides a sealed passageway for fluid, which may be pressurized fluid, to flow into or out of any type of container, and is preferably made of a disposable and sterilizable material.

Durable tower system

Fig. 17 shows tower system 2000. Tower system 2000 is durable (i.e., non-disposable) hardware that houses the various devices of photopheresis kit 1000, such as cassette 1100, radiation chamber 700, and centrifuge bowl 10 (FIG. 1). Tower system 2000 performs valving, pumping, and overall control and drive of fluid flow through disposable photopheresis kit 1000. Tower system 2000 performs all necessary control functions automatically through the use of a suitably programmed controller, such as a processor or integrated circuit, connected to all required components. Tower system 2000 may be reused, although new disposable tools must be discarded after each photopheresis treatment session. Tower system 2000 is modified to perform a number of extracorporeal blood circulation procedures, such as apheresis, by appropriately programming the controller or by changing some of its components.

Tower system 2000 has a housing with an upper portion 2100 and a base portion 2200. Base portion 2200 has a top 2201 and a bottom 2202. Wheels 2203 are provided at or near the bottom 2202 of base portion 2200 so that tower system 2000 is mobile and can be easily moved from room to room in a hospital. Preferably, front wheels 2203 are rotatable about a vertical axis to facilitate maneuvering and movement of tower system 200. As best shown in fig. 22, the top 2201 of the base portion 2200 has a top surface 2204 with a control panel 1200 disposed therein (see fig. 22). In fig. 17, a cassette 1100 is loaded on a control panel 1200. The base portion 2200 also has hooks (not shown), or other connectors, to hang the plasma collection bag 51 and the processing bag 50 therefrom. The hooks may be positioned anywhere on tower system 2000 so long as their positioning does not interfere with the function of the system during treatment. Base portion 2200 has a photoactivation chamber 750 (FIG. 18) positioned behind door 751. Additional hooks (not shown) are provided on tower system 2000 for hanging saline and anticoagulant bags. Preferably, the hooks are positioned on the upper portion 2100.

Photoactivation chamber 750 (FIG. 18) is disposed in base portion 2200 of tower system 2000 between top 2201 and bottom 2202 behind door 751. Door 751 is hingedly connected to base portion 2200 and provides access to photoactivation chamber 750 and allows an operator to close photoactivation chamber 750 so that UV light does not leak into the surrounding environment during treatment. A groove 752 is provided to allow tubes 1112, 1117 (fig. 1) to enter photoactivation chamber 750 when radiation chamber 700 is loaded and door 751 is closed. The photoactivation chamber is discussed in detail below with reference to fig. 16 and 18.

The upper portion 2100 is located atop the base portion 2200. Centrifuge chamber 2101 (FIG. 19) is located in upper portion 2100 behind centrifuge chamber door 2102. Centrifuge chamber door 2102 has window 2103 so that the operator can see inside centrifuge chamber 2101 and monitor for any problems. The window 2103 is constructed of glass that is thick enough to withstand any forces exerted on it by accident when the centrifugal bowl is rotated at speeds greater than 4800 PPM. Preferably, window 2103 is constructed of shatterproof glass. Door 2102 is rotatably connected to upper portion 2100 and has an automatic locking mechanism that is activated by a system controller when the system is in operation. Centrifuge chamber 2101 is discussed in detail below with reference to FIG. 19.

Preferably, deck 1200 is located on top surface 2204 of base portion 2200 at or near the front of tower system 2000, while upper portion 2100 extends upwardly from base portion 2200 near the rear of tower system 2000. This allows the operator to easily access control panel 1200 while providing the operator access to centrifuge chamber 2101. The vertical configuration is achieved by designing tower system 2000 to have centrifugation chamber 2101 in upper portion 2100 and light activation chamber 750 and panel 1200 in base portion 2200. Also, tower system 2000 has a reduced footprint and reduces the amount of floor space that occupies the hospital at a premium. Tower system 2000 is maintained at a height of less than sixty inches so that it does not obstruct the view of the machine as it is moved around the hospital transport to form the rear occupancy. In addition, panel 1200 in a substantially horizontal position will provide an operator with a location to place the apparatus of photopheresis kit 1000 when loading other apparatus, facilitating ease of loading. Tower system 2000 is sufficiently robust to withstand the forces and vibrations associated with a centrifugal process.

The monitor 2104 is placed over a window 2103 in the centrifuge chamber door 2102. Monitor 2104 has a display area 2105 for visually displaying data to an operator, such as a user interface for data entry, loading instructions, graphics, warnings, alarms, treatment data, and treatment progress. The monitor 2104 is connected to and controlled by the system controller. A data card port 2001 is provided on the side of the monitor 2104. Data card receiving port 2001 is provided to slidably receive data card 1195 (FIG. 1) provided by each disposable photopheresis kit 1000. As described above, data card 1195 can be pre-programmed to store a system controller that provides various data to tower system 2000. For example, data card 1195 may be programmed to transmit information so that the system controller can ensure that: (1) the disposable photopheresis kit is compatible with the blood-driven device carried therein; (2) the photopheresis kit can operate the required treatment process; (3) the disposable photopheresis kit is of a certain brand or make. Data card port 2001 has the necessary hardware and circuitry to read data from and write data to data card 1195. Preferably, data card port 2201 records treatment data to data card 1195. Such information may include, for example: collection time, collection volume, processing time, volumetric flow rate, any alarms, faults, disturbances or any other desired data in the process. Although data card port 2001 is provided on monitor 2104, it may be located anywhere on tower system 2000 so long as it is connected to a system controller or other suitable control device.

A. Photoactivation chamber for containing radiation chamber

Referring now to fig. 16 and 18, photoactivation chamber 750 is shown in cross-section. The photoactivation chamber 750 is formed by a housing 756. Housing 756 fits within base portion 2200 of tower system 2000 behind door 751 (fig. 17). The photoactivation chamber 750 has a number of electrical connection ports 753 provided on the rear wall 754. The electrical connection port 753 is electrically connected to a power supply. Photoactivation chamber 750 is designed to accommodate UVA light assembly 759 (fig. 16). When fully loaded in photoactivation chamber 750, electrical contacts (not shown) located on contact wall 755 of UVA light assembly 759 make electrical connection with electrical connection ports 753. This electrical connection allows electrical power to be supplied to the UVA lamps 758 so that they may be activated. Preferably, three electrical connections are provided for each set of UVA lights 758. A more preferred UVA light assembly 759 has two sets of UVA lamps 758 that form a space into which the radiation chamber 700 can be inserted. The power supply to the UVA lamp 758 is controlled by a suitably programmed system controller using a switch. During the photopheresis treatment period, the UVA lights 758 are activated and deactivated by the controller as needed.

A vent 757 is provided at the top end of housing 756 near rear wall 754 of photoactivation chamber 750. Vent 757 connects to a rear vent tube 760 of straight through tower system 2000. As heat generated by UVA lamp 758 builds up in photoactivation chamber 750 during treatment therapy, the heat exits photoactivation chamber 750 through vent 757 and vent tube 760. Heat exits tower system 2000 through tower housing aperture 761, which is located behind tower system 2000, away from the patient and the operator.

The light activation chamber 750 also includes a guide slot 762 for receiving the radiation chamber 700 and maintaining the radiation in a vertical position between the UVA lamps 758. The guide 762 is located at or near the bottom of the photoactivation chamber 750. Preferably, a leak detection circuit 763 is provided below the guide 762 to detect any fluid leaking out of the radiation chamber 700 during, before or after operation. The leak detection circuit 762 has two electrodes in a U-shape that are located on a flex circuit that is adhesively supported. Designing the electrodes allows the use of short-circuit pairs to interrupt the test. One end of each electrode is connected to the integrated circuit and the other end of each electrode is connected to the solid state switch. Solid state switches can be used to check the continuity of the electrodes. By closing the switch, the electrodes are short-circuited to each other. The integrated circuit then detects the short circuit. Closing the switch results in a condition equivalent to wetting (i.e., leakage) of the electrodes. If the electrodes are damaged in any way, the continuity check will fail. This is a positive indication that the electrode is not damaged. Such testing may be performed periodically during each system startup or normal operation to ensure that the leak detection circuit 762 is functioning properly. The leak detection circuit 762 helps to ensure that leaks are not overlooked throughout the treatment period due to damage to the circuitry detecting the leak. A circuit diagram of the leak detection circuit 762 is provided in fig. 20.

B. Centrifugal chamber

FIG. 19 shows centrifuge chamber 2101 with the housing of tower system 2000 removed in cross-section. A turning gear 900 (also shown in cross-section) capable of utilizing 1-omega and 2-omega rotation techniques is located within centrifuge chamber 2101. The rotating apparatus 900 includes a rotating bracket 910 and a bowl securing plate 919 for rotatably securing the centrifugal bowl 10 (FIG. 1). Housing 2107 of centrifuge chamber 2101 is preferably made of aluminum or some other lightweight, strong metal. Alternatively, other rotating systems may be used in tower system 2000, such as described in U.S. Pat. No.3,986,442, which is incorporated herein by reference in its entirety.

The leak detection circuit 2106 is provided on the rear wall 2108 of the housing 2107. A leak detection circuit 2106 is provided to detect any leaks in the centrifuge bowl 10 or connecting tubing during processing. The leak detection circuit 2106 is the same as the leak detector circuit 762 described above. A circuit diagram of the leak detection circuit 2106 is provided in fig. 21.

C. Fluid flow control panel

FIG. 22 shows control panel 1200 of tower system 2000 (FIG. 17) without cassette 1100 loaded thereon. Control panel 1200 performs valving and pumping to drive and control fluid flow throughout photopheresis kit 1000. Preferably, deck 1200 is a separate plate 1202 that is secured to base portion 2200 of tower system 2000 by screws or other securing means, such as screws, nuts, or clips. The plate 1202 may be made of steel, aluminum, or other durable metal or material.

Faceplate 1200 has five peristaltic pumps, namely whole blood pump 1301, return pump 1302, recirculation pump 1303, anticoagulant pump 1304, and red blood cell pump 1305, extending from plate 1202. Pumps 1301 & 1305 are arranged on plate 1202 such that when cassette 1100 is loaded on plate 1200 for operation, pump loop tubes 1120 & 1124 extend over and surround pumps 1301 & 1305 (FIG. 25).

A bubble sensor assembly 1204 and an HCT sensor assembly 1205 are provided on the plate 1202. Bubble sensor assembly 1204 has three tube slots 1206 for receiving tubes 1114, 1106, and 1119 (FIG. 25). Bubble sensor assembly 1204 uses ultrasonic energy to monitor tubes 1114, 1106, and 1119 for density differences that can indicate the presence of air in the liquid normally passing therethrough. Tubes 1114, 1106, and 1119 are monitored as these lines are connected to the patient. The bubble sensor assembly 1204 is operatively connected to and transmits data to the system controller for analysis. If a bubble is detected, the system controller will shut down and prevent fluid flow into the patient by moving the piezo actuators 1240 and 1242 to a raised position to close the tubes 1114, 1106, and 1119, thereby forcing the tubes 1114, 1106, and 1119 against the cassette 1100 and/or shutting off the appropriate pumps as described above. HCT sensor assembly 1205 has a slot 1207 for receiving HCT assembly 1125 of tubes 1116. The HCT sensor assembly 1205 monitors the tube 1116 for the presence of red blood cells by using a photosensor. The HCT sensor assembly 1205 is also operatively connected and transmits data to the system controller. Once the HCT sensor assembly 1205 detects the presence of red blood cells in tube 1116, the system controller will take an appropriate action, such as deactivating the appropriate pump or activating one of the pressure actuators 1243 and 1247, to stop fluid flow through tube 1116.

Faceplate 1200 also has five piezo actuators 1243 and 1247, and three piezo actuators 1240 and 1242 strategically located on plate 1202 such that each piezo actuator 1240 and 1247 is connected to a respective aperture 1137 and 1157 when cassette 1100 is loaded for operation on plate 1200. Pressure actuator 1240 and 1247 may be moved between a lowered position and a raised position. As shown in fig. 22, piezo actuators 1243 and 1247 are in a lowered position and piezo actuator 1240 and 1242 are in a raised position. When in the raised position, and when the cassette 1100 is loaded on the panel 1200 as shown in FIG. 25, the pressure actuator 1240 and 1247 will extend through the respective aperture 1137 or 1157 and press against the portion of the flexible tubing aligned with that aperture, thereby pinching closed the flexible tubing so that fluid cannot pass therethrough. When in the lowered position, pressure actuator 1240 and 1247 do not protrude through apertures 1137 and 1157 and therefore do not compress the flexible tubing.

The piezo actuators 1243 and 1247 are spring retracted so that their default positions are about to move to the lowered position unless activated. Each piezo actuator 1243-1247 is controlled individually and can be raised or lowered independently of each other. Instead, piezo actuators 1240 and 1242 are connected together. Thus, when one piezo actuator 1240 and 1242 is lowered or raised, the other two piezo actuators 1240 and 1242 are lowered or raised accordingly. Additionally, piezo actuators 1240 and 1242 are spring loaded so that their default position is to be moved to the raised position. Thus, if the system loses power during treatment, piezo actuator 1240 and 1242 will automatically move to the raised position, closing tubes 1114, 1116 and 1119, and preventing fluid from entering or exiting the patient.

Referring now to fig. 23 and 24, the panel 1200 also includes a system controller 1210, a cylinder assembly 1211, a manifold assembly 1213, a pump cable 1215, a pump motor cable 1216 and a timing belt assembly 1217. System controller 1210 is a suitably programmed integrated circuit operatively connected to the necessary components of the system to perform all of the functions, interactions, decisions, and responses described above and necessary to perform photopheresis treatment in accordance with the present invention. Cylinder assembly 1211 connects each pressure actuator 1240-1247 to a pneumatic cylinder. Air ports 1212 are provided on various elements of the faceplate 1200 as needed to connect the air tubes to the device and to an appropriate one of the manifolds 1213. Thus, air may be provided to the device when necessary to brake the necessary components, such as pressure valve 1240 and 1247. All of these functions and synchronization are controlled by the system controller 1210. Timing belt assembly 1217 is used to coordinate the rotation of rotating clamp 1203. Finally, plate 1202 includes a number of holes 1215, 1219, 1220, 1221, and 1218 so that the various components of deck 1200 may be properly loaded and so that deck 1200 may be secured to tower system 2000. In particular, pump 1301-.

1. Box clamping mechanism

Referring now to fig. 22 and 25, a method of loading and securing the cassette 1100 to the panel 1200 will now be discussed. In order for system 2000 to perform photopheresis treatment, cassette 1100 must be properly loaded onto deck 1200. Because of the incorporation of the piezo actuator valve system in the present invention, the cartridge 1100 must be properly secured to the faceplate 1200 and not become dislodged or misplaced when the piezo actuators 1240 and 1247 close portions of the flexible tubing by pressing the flexible tubing against the cover 1130 (FIG. 3) of the cartridge 1100. However, this need is contrary to the desired goal of easily loading the cassette 1100 on the panel 1200 and reducing operator error. All these objects are achieved by the cassette holding mechanism described below.

To facilitate clamping of the cassette 1100 to the panel 1200, the panel 1200 is provided with two catches 1208 and two pivoting clips 1203 and 1223. The catch 1208 has a slot 1228 adjacent the middle of the top plate. The catches 1208 are secured to the plate 1202 in a predetermined position such that they are substantially the same spacing as the spacing between the tabs 1102 and 1103 on the cassette 1100 (fig. 2). Rotating clamps 1203 and 1223 are illustrated in a closed position. However, rotating clamps 1203 and 1223 can be rotated to an open position (not shown) either manually or by automatic actuation of a pneumatic cylinder. Rotating clamps 1203 and 1223 are spring loaded by a torque spring to automatically return to the closed position when no additional torque is applied. Rotating clamps 1203 and 1223 are connected together by timing belt assembly 1217 (FIG. 24).

Referring now to FIG. 23, timing belt assembly 1217 comprises a timing belt 1226, a torque spring housing 1224, and a take-up assembly 1225. Timing belt assembly 1217 causes the rotation of rotating clamps 1203 and 1223 to be coordinated so that if one clamp rotates, the other clamp also rotates in the same direction and by the same amount. In other words, rotating clamps 1203 and 1223 are coupled. Tensioning assembly 1217 ensures that timing belt 1226 engages and rotates synchronized rotating clamps 1203 and 1223 with sufficient tension. The torque spring housing 1224 provides an enclosure for a torque spring that twists the rotating clamps 1203 and 1223 to a closed position.

Referring back to fig. 22 and 25, when the cassette 1100 is loaded onto the panel 1200, the cassette 1100 is positioned at an angle to the panel 1200 and the tabs 1102 and 1103 (fig. 2) are aligned with the catches 1208. The cassette 1100 is moved so that the tabs 1102 and 1103 are slidably inserted into the catches 1208. At this point rotating clamps 1203 and 1223 are in the closed position. As tabs 1102 and 1103 are inserted into catch 1108, the rear of cassette 1100 (i.e., the side opposite tabs 1102 and 1103) contacts rotating clamps 1203 and 1223. As a result of the downward force on cassette 1100, rotating clamps 1103 and 1123 will rotate to the open position, allowing the rear of cassette 1100 to move downward to a position below the projecting portions 1231 of rotating clamps 1203 and 1223. Once the cassette 1100 is in this position, the rotating clamps 1203 and 1223 spring back through the force applied by the torque spring and rotate back to the closed position, locking the cassette 1100 in place. When in the locked position, the cassette 1100 may be subjected to upward and lateral forces.

To remove cassette 1100 after the treatment session is complete, rotating clamps 1203 and 1223 are manually or automatically rotated to an open position. Automatic rotation is achieved by an air cylinder connected to the air line and system controller 1210. Once rotating clamps 1203 and 1223 are in the open position, cassette 1100 is removed by simply raising and disengaging slide tabs 1102 and 1103 from catch 1208.

2. Self-loading peristaltic pump

Referring to FIG. 24, peristaltic pumps 1301 and 1305 are provided on faceplate 1200 and are used to drive fluid along a desired path through photopheresis kit 1000 (FIG. 1). Activation, inhibition, synchronization, speed, consistency, and all other functions of peristaltic pump 1301-. Peristaltic pumps 1301 and 1305 have the same structure. However, the placement of the peristaltic pumps 1301 and 1305 on the panel 1200 indicates the function of the peristaltic pumps 1301 and 1305 with respect to which fluid is driven and along which path. This is because the arrangement of the peristaltic pumps 1301-.

Referring now to fig. 28 and 29, whole blood pump 1301 is shown in detail. With the understanding that peristaltic pump 1302-1305 are equivalent, the structure and function of a whole blood pump will be described. Whole blood pump 1301 has motor 1310, position sensor 1311, pneumatic cylinder 1312, pneumatic actuator 1313, rotor 1314 (best shown in fig. 30), and housing 1315.

Rotor 1314 is rotatably mounted in housing 1315 and is operatively connected to a drive shaft 1316 of motor 1310. In particular, rotor 1314 is mounted within curved wall 1317 of housing 1315 so that it can be rotated about axis A-A by motor 1310. When rotor 1314 is mounted within housing 1315, there is a space 1318 between rotor 1314 and curved wall 1317. This space 1318 is the tube pumping area of whole blood pump 1301, in which pump loop tube 1121 (fig. 33) is installed when loaded for pumping. The position sensor 1316 is coupled to a drive shaft 1316 of the motor 1310 such that the rotational position of the rotor 1314 may be monitored by monitoring the drive shaft 1316. The position sensor 1311 is operatively connected to and transmits data to the system controller 1210 (fig. 24). By analyzing this data, the system controller 1210, which is also coupled to the motor 1310, can activate the motor 1310 to cause the rotor 1314 to assume any desired rotational position.

The housing 1315 also includes a housing flange 1319. Housing flange 1319 is used to secure whole blood pump 1310 to plate 1202 of faceplate 1200 (fig. 22). More particularly, screws extend through screw holes 1320 of housing flange 1319 to threadingly engage holes in plate 1202. The housing flange 1319 also includes apertures (not shown) through which the pneumatic actuator 1313 extends. The aperture is sized so that the lower pneumatic actuator 1313 can move between the raised and lowered positions without significant obstruction. Pneumatic actuator 1313 is activated and deactivated by pneumatic cylinder 1312 through the use of air in a piston-like manner. The pneumatic cylinder 1312 includes an air inlet hole 1321 for connecting an air supply line. When air is supplied to pneumatic cylinder 1312, the pneumatic actuator extends upwardly through housing flange 1319 to a raised position. When air stops being supplied to pneumatic cylinder 1312, the pneumatic actuator retracts into pneumatic cylinder 1312, returning to the lowered position. The system controller 1210 (fig. 22) controls the supply of air to the air intake 1321.

Curved wall 1317 of housing 1315 contains two slots 1322 (only one shown). Slots 1322 are located on substantially opposite sides of curved wall 1317. Slots 1322 are provided for pump loop tube 1121 (fig. 33) into tube pumping region 1318. More particularly, pump inlet portion 1150 and outlet portion 1151 (FIG. 33) of pump loop tube 1121 pass through slots 1322. referring now to FIGS.

Referring now to fig. 30 and 31, rotor 1314 is shown removed from housing 1315 so that its components may be more clearly shown. Rotor 1314 has a top surface 1323, an angled guide 1324, a rotor flange 1325, two guide rollers 1326, two drive rollers 1327, and a rotor bottom 1328. Guide rollers 1326 and drive rollers 1327 are rotatably secured about cores 1330 between rotor floor 1328 and bottom surface 1329 of rotor flange 1325. As best shown in fig. 29, core 1330 fits into hole 1331 of rotor bottom 1328 and recess 1332 in bottom surface 1329. Guide rollers 1326 and drive rollers 1327 are mounted around core 1330 and are able to rotate thereabout. Preferably, two guide rollers 1326 and two drive rollers 1327 are provided. More preferably, a guide roller 1326 and a drive roller 1327 are provided on the rotor 1314 so as to be in an alternating pattern.

Referring to fig. 29 and 31, drive roller 1327 is provided to press against a portion of pump loop tube 1221 that is loaded in tube pumping region 1318 against the inner face of curved wall 1317 as rotor 1314 is rotated about axis a-a, thereby deforming the tube and forcing fluid through the tube. Changing the rotational speed of rotor 1314 will correspondingly change the rate of fluid flow through the tube. Guide rollers 1326 are provided to keep the portion of pump loop tube 1121 that is housed within tube pumping zone 1318 properly aligned during pumping. Additionally, guide rollers 1326 help properly load the pump tube loop 1211 in the tube pumping region 1318. Although the guide rollers 1326 are illustrated as having the same cross-section, the top plate of the guide rollers is preferably tapered to obtain a sharper edge adjacent their outer diameter. The tapered roof results in a guide roller with an asymmetrical cross-section. The tapered embodiment helps to ensure proper loading of the tubing into the tubing pumping area.

Rotor 1314 also includes a cavity 1328 extending from its center. The cavity 1328 is designed to couple the rotor 1314 to the drive shaft 1316 of the motor 1310.

Referring now to fig. 30 and 32, the rotor flange has an opening 1333. Opening 1333 is defined by a leading edge 1334 and a trailing edge 1335. The use of the terms front and rear assume that rotor 1314 rotating in a clockwise direction is forward and rotor 1314 rotating in a counterclockwise direction is reverse. However, the present invention is not limited thereto, and may be modified to a counterclockwise pump. Leading edge 1334 slopes downward into opening 1333. The trailing edge 1335 extends upwardly from the top surface of the rotor flange 1325 above the leading edge 1334. A leading edge is provided for the trailing edge for locking and feeding pump loop tube 1121 into tube pumping region 1318 when rotor 1314 is rotating in the forward direction.

Rotor 1314 also has an angled guide 1324 extending upward at a reverse angle from rotor flange 1325. Angled guide 1324 is provided to move pump loop tube 1121 toward rotor flange 1325 when rotor 1314 is rotated in the forward direction. Preferably, angled guide 1324 has a raised ridge 1336 running along top surface 1323 for manual engagement by an operator when desired. More particularly, angled guide 1314 is positioned forward of leading edge 1334.

Referring now to fig. 28 and 33, whole blood pump 1301 can automatically load and unload pump loop tube 1121 into and out of pumping region 1318. When cassette 1100 is loaded onto deck 1200 (fig. 25), rotor 1314 is rotated to the loading position where angled guide 1324 will face cassette 1100 using position sensor 1311. More particularly, rotor 1314 is pre-positioned in a position such that when cassette 1100 is secured to the faceplate, the angled guide is positioned between inlet portion 1150 and outlet portion 1151 of pump loop 1121, as shown in FIG. 13. When cassette 1100 is secured to deck 1200, pump loop tube 1121 extends up and around rotor 1314. With the pneumatic actuator 1313 in the lowered position.

Once cassette 1100 is properly secured and the system is ready, rotor 1314 is rotated in a clockwise direction (i.e., forward direction). As rotor 1314 rotates, pump tube loop 1121 is contacted by angled guide 1324 and moved against the top surface of rotor flange 1325. The portion of pump loop tube 1121 that moves against rotor flange 1325 is then contacted by trailing edge 1325 and passes down through opening 1333 into tube pumping region 1318. Guide rollers 1326 are provided directly behind opening 1333 to further position the tubing properly within the tube pumping chamber for pumping by drive rollers 1327. When loaded, inlet portion 1150 and outlet portion 1151 of pump loop tube 1121 pass through slots 1322 of curved wall 1317. One and a half turns are required to fully load the pipeline.

To automatically unload pump tube loop 1121 from whole blood pump 1301 after treatment, rotor 1314 is rotated to a position in which opening 1333 is aligned with slot 1322 through which outlet portion 1151 passes. Once aligned, the pneumatic actuator 1313 is activated and extends to a raised position, contacting and raising the outlet portion 1151 to a height above the trailing edge 1335. Rotor 1314 is then rotated in a counterclockwise direction to bring trailing edge 1335 into contact with pump loop tube 1121 through opening 1333 and remove pump loop tube 1121 from tube pumping region 1318.

D infrared communication

Referring to FIG. 34, tower system 2000 (FIG. 17) preferably also includes a wireless infrared ("IR") communication interface (not shown). The wireless IR interface consists of three main elements: system controller 1210, IRDA protocol integrated circuit 1381, and IRDA interface 1382. The IR communication interface can transmit and receive data from a remote computer or other device with IR capabilities via IR signals. In sending data, the system controller 1210 sends serial communication data to the IRDA protocol chip 1381 to buffer the data. The IRDA protocol chip 1381 adds additional data and other communication information to the transfer string, which is then sent to an IRDA transceiver (transceiver) 1382. Transceiver 1382 converts the electrical transmission data into coded light pulses and transmits them to a remote device via an optical transmitter.

In receiving data, IR data pulses are received by a photodetector located on the transmitter chip 1382. The transceiver chip 1382 converts the optical light pulses into electrical data and sends the data stream to the IRDA protocol chip 1381 where the electrical signals are broken into control and additional IRDA protocol content. The remaining data is then sent to the system controller 1210 where the data stream is parsed by the communication protocol.

By incorporating an IR communication interface into tower system 2000, real-time data regarding the course of treatment may be transmitted to a remote device for recording, analysis, or further transmission. Data may be sent via IR signals to tower system 2000 to control therapy or to change protocols in an unattended state. In addition, the IR signal does not interfere with other hospital equipment, such as radio frequencies, as does other wireless transmission methods.

Photopheresis treatment procedure

Referring collectively to fig. 26, which shows a flow chart of an embodiment of the present invention including light activation of the buffy coat, and fig. 27, which shows a schematic of a device that can be used with this embodiment, the process begins 1400 with connection to a patient 600(1400) by means of a needle adapter 1193 carrying a needle and a needle adapter 1194 carrying another needle, where the needle adapter 1193 is used to draw blood and the needle adapter 1194 is used to return processed blood and other components. Saline bag 55 is connected by connector 1190 and anticoagulant bag 54 is connected by connector 1191. Actuators 1240, 1241 and 1242 are turned on, anticoagulant pump 1304 is turned on, and saline actuator 1246 is turned on, so that all disposable tubing sets are filled with saline 55 and anticoagulant 54 (1401). Centrifuge 10 is started 1402 and the blood-anticoagulant mixture is pumped to centrifuge bowl 10(1403) at a 1: 10 speed ratio controlled by A/C pump 1304 and WB pump 1301.

When the collection reaches 150mL 1404, the return pump 1302 is set to the speed 1405 of the collection pump 1301 until red blood cells 1406 are detected by the HCT sensor (not shown) in the centrifuge chamber 1201 (FIG. 19). The packed red blood cells and buffy coat are now accumulated in the rotating centrifuge bowl and are slowly pumped out by the processor control at a rate that maintains the red blood cell line at the sensor level.

Then, while controlling the speed to maintain the cell line at interface level 1048, the red blood cell pump 1305 is set to 35% inlet pump speed 1407 until collection cycle volume 1409 is reached, upon which the red blood cell pump 1305 is turned off 1410 and the fluid path through HCT sensor 1125 to processing bag 50 is opened by lowering actuator 1244 and stopped 1411 when the HCT sensor 1125 detects red blood cells. "collection cycle volume" is defined as the total blood treatment divided by the number of collection cycles, for example 1500ml of white blood cell treatment may require 6 cycles, and therefore 1500/6 is a volume of 250 ml. As the whole blood continues to be transferred from the patient to the bowl at 1410, the red blood cell pump is turned off and the red blood cells will accumulate and will express the buffy coat from within the bowl 10. The red blood cells are used to express the buffy coat and will be detected by a discharge Hematocrit (HCT) sensor to indicate that the buffy coat has been collected.

If another cycle 1412 is required, the centrifuge 10 discharge path is returned to the plasma bag 51(1413) and the speed of the red blood cell pump 1305 is increased to the pump speed 1413 of the inlet pump 1301 until red blood cells 1414 are detected, which is the beginning of the second cycle. If another cycle 1412 is not required, centrifuge 10 is shut down 1415 and inlet pump 1301 and anticoagulant pump 1304 are set at KVO speed, 10ml/hr in this embodiment. The exit path leads to a plasma bag 51(1416), the red blood cell pump 1305 speed is set at 75ml/min (1417), the recirculation pump 1303 and light activated lamp are turned on for a sufficient time to treat the buffy coat 1418, which time is calculated by the controller based on the volume and type of disease being treated.

When the bowl 10 is empty 1419, the red cell pump 1305 is turned off 1420 and the plasma bag 51(1421) is emptied by opening actuator 1247 and continuing to run back to the pump 1302. When the plasma bag 51 is empty, the return pump 1302 is turned off 1422, and when the light activation process is complete 1423, the processed cells are returned from the plate 700 to the patient 1424 through the return pump 1302. Saline is used to flush the system and the flush is returned to the patient, completing the procedure 1425.

The anticoagulant, blood from the patient, and fluid returned to the patient are all monitored by air detectors 1204 and 1202, and fluid returned to the patient passes through the sedimentation chamber and filter 1500. The rotation of the pumps 1304, 1301, 1302, 1303 and 1305, the actuators 1240, 1241, 1242, 1243, 1244, 1245, 1246 and 1247, and the bowl 10 are all controlled by a programmed processor in the tower system.

This process and related apparatus are significantly superior to existing processes and apparatus in that the present invention allows the buffy coat to reside in the bowl for a longer period of time because the buffy coat is collected in the bowl while the red blood cells are drawn when centrifuging, keeping more buffy coat in the bowl until the desired amount of buffy coat is collected before the collected buffy coat cells are drawn. Platelets, white blood cells and other buffy coat fractions can also be separated, or as described, red blood cells can be collected, rather than merely returning them to the patient with the plasma.

It was found that increasing the time of rotational movement of the buffy coat 810 in the centrifuge bowl 10 produced a "cleaner composition" of the buffy coat 820. By "cleaner composition" is meant a decrease in hematocrit (HCT%). HCT% is the amount of red blood cells present per volume of buffy coat. The amount of time that the buffy coat 820 is rotationally moved in the centrifuge bowl 10 can be maximized in the following manner. First, when the centrifugal bowl 10 is rotated, whole blood 800 is supplied to the first bowl channel 420. As described above, the whole blood 800 separates into buffy coat 820 and RBC's 810 as it moves outward on top of the lower plate 300. The second drum channel 410 and the third drum channel 240 are now closed. The whole blood 800 continues to flow until the separation volume 220 is filled with a combination of buffy coat 820 near the top and RBC's 810 near the bottom of the centrifuge bowl 10. By removing the RBC's 810 from the centrifuge bowl 10 only through the second bowl channel 410, additional volume is created for the inflow of whole blood 800, and the non-removed buffy coat 820 is subjected to a rotational force for an extended period of time. As the centrifuge bowl 10 continues to rotate, some of the RBC's 810 entrained in the buffy coat 820 are pushed to the bottom of the centrifuge bowl 10 and away from the third bowl channel 740 and the buffy coat 820. Thus, when the third bowl channel 740 is opened, the removed buffy coat 820 has a lower HCT%. By controlling the inflow rate of whole blood 800 and the outflow rate of the buffy coat 820 and RBC's 810, a steady state of the buffy coat 820 with a reasonably constant HCT% can be produced.

The present invention achieves the goal of reduced batch processing and improved yields, which reduce the treatment time necessary to fully treat a patient. For an average size adult, 90-100 ml of buffy coat/white blood cells must be collected for a complete photopheresis treatment. To collect this amount of buffy coat/white blood cells, the present invention requires processing about 1.5 liters of whole blood. The desired buffy coat/white blood cell volume can be removed from 1.5 liters of whole blood using the present invention in about 30-45 minutes, collecting about 60% or more of the total buffy coat/white blood cell volume processed by the separation process. The collected buffy coat/white blood cells have an HCT of 2% or less. In contrast, one prior device, UVAR XTS, took 90 minutes to process 1.5 liters of whole blood to obtain sufficient buffy coat/white blood cell mass. The UVAR XTS only collects about 50% of the total buffy coat/white blood cells treated by the separation process. HCT of buffy coat/leukocytes collected by UVAR XTS approximately2% but not substantially less than 2%. Another prior art device, the Cobe Spectra of Gambro^TMTo collect a sufficient buffy coat/white blood cell volume, 10 liters of whole blood need to be processed. This typically takes about 150 minutes, collecting only about 10-15% of the total buffy coat/white blood cells treated by the separation process, and has an HCT of about 2%. Thus, it has been found that while existing devices and systems require about 152 to 225 minutes to isolate, treat and reinfuse the desired amount of white blood cells or buffy coat, the present invention can perform the same function in less than 70 minutes. These times do not include the time of preparation or initial patient. This time refers only to the total time the patient is connected to the system.

Claims (10)

1. An apparatus for separating components of a fluid, comprising:

a housing having an upper housing end and a lower housing end, wherein said housing increases in diameter from said upper housing end to said lower housing end, said lower housing end having a housing floor and said housing upper end having a housing outlet, said housing rotating about a central axis;

the housing includes a core in the interior space; the core having an outer wall, an upper core end and a lower core end; the core is connected with the shell along with the rotation of the core; and providing a separation space between the core and the housing; the core end having a cavity connector and a cavity connector top surface;

a first chamber for providing fluid communication from the housing outlet through the chamber connector and then radially outwardly through the wick to the fluid separation space;

a second chamber providing fluid communication extending axially along the central axis from the housing outlet to the housing bottom;

a connection sleeve forming a chamber with the chamber connector and providing fluid communication between the housing outlet and the separation space.

2. The apparatus of claim 1, wherein the first cavity extends radially outward to the housing about a mid-position of the housing bottom.

3. The device of claim 1, wherein the cavity extends radially outward to the housing through one to eight passages around a mid-position of the housing bottom.

4. The device of claim 1, wherein the outer wall of the core increases in diameter from the upper end to the lower end.

5. The apparatus of claim 1, wherein a connecting sleeve is secured to the apparatus proximate the housing outlet of the housing for rotation therewith, the connecting sleeve fluidly connecting the first drum passage, the second drum passage, and the chamber.

6. An apparatus for separating components of a fluid, comprising:

a housing having an upper housing end and a lower housing end, wherein said housing increases in diameter from said upper housing end to said lower housing end, said lower housing end having a housing floor and said housing upper end having a housing outlet, said housing having an interior space and rotating about a central axis;

a top core having an outer wall, an upper top core end and a lower top core end; the top core is connected with the shell along with the rotation of the top core; a top coaxial space occupying the interior space of the housing: and providing a top separation space between the core and the shell;

the upper mandrel end has a cavity connector; the cavity connector having a first cavity wall extending downwardly from a top surface of the cavity connector; the cavity connector also has an interior cavity wall within the first cavity wall and extending downwardly from the top surface; the interior chamber wall has a top wall end and a bottom wall end;

an upper plate having a top surface, a bottom surface, a second cavity wall extending over the top surface; the upper plate is in close fit with the lower top core end along with the rotation of the upper plate;

the second cavity wall (402A) overlaps the first cavity wall (401A) to form a cavity (400A) having an upper cavity end (480A) and a lower cavity end (490A); the cavity (400A) extends axially through the core (200A) forming a first drum channel (420A) for the inflow of the fluid (800) and the cavity (400A) is in fluid communication with a separation space (220A) through a slot (305A);

a bottom core (201A) having an outer wall (211A), a top surface (309A) for contacting and connecting with the bottom surface (297A) of the upper plate (299A) as it rotates; an upper core end (206A), a lower core end (296A), said top surface (309A) having a notch (186A) and a slot (305A), and a cavity wall (324A) having an upper wall end (324C) and a lower wall end (324B); the bottom core occupies the bottom coaxial space of the interior space (710A) of the housing (100A);

an upper wall end (324C) of the chamber wall (324A) engaging a bottom wall end (325B) of the inner chamber wall (325A) to form an inner chamber (400B) having an upper chamber end (325C) and a lower chamber end (324B); said inner chamber (400B) forming a second bowl channel (410A) for removing a first separated fluid component (810);

a lower plate (300A) having a top surface (730A), a bottom surface (730B), and a hollow cylinder (320A) near the center of the lower plate (300A); the hollow cylinder (320A) having an opening (302A) that engages a lower wall end (324B) of a cavity (324A); and said lower plate (300A) having a perimeter for forming a tight fit with the lower core end (296A) as it rotates;

a coupling sleeve having a sleeve flange surrounding the cavity mounting groove; said chamber mounting recess and the top surface of the chamber connector engaging to form a rotor chamber for removal of the second separated fluid component; the adapter sleeve is secured to the device for rotation therewith and also adjacent the housing outlet of the housing.

7. The device of claim 6, wherein the outer wall (210A) of the top core (200A) increases in diameter from the upper end (205A) to the lower end (295A).

8. The apparatus of claim 6, wherein the outer wall (211A) of the bottom core (201A) increases in diameter from the upper end (206A) to the lower end (296A).

9. The device of claim 6, wherein the outer wall (210A) of the top core (200A) increases in diameter from the upper end (205A) to the lower end (295A), and the outer wall (211A) of the bottom core (201A) increases in diameter from the upper end (206A) to the lower end (296A).

10. The apparatus of claim 6, wherein the cavity (400A) has a height (404A), the cavity wall (324A) has a height (324F), and the height (404A) of the cavity (400A) is one-third to four-times the height (324F) of the cavity wall (324A).