WO2003011385A1 - Flow cytometer shunt - Google Patents
Flow cytometer shunt Download PDFInfo
- Publication number
- WO2003011385A1 WO2003011385A1 PCT/US2002/023780 US0223780W WO03011385A1 WO 2003011385 A1 WO2003011385 A1 WO 2003011385A1 US 0223780 W US0223780 W US 0223780W WO 03011385 A1 WO03011385 A1 WO 03011385A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- flow cytometer
- cells
- dye
- marker
- recited
- Prior art date
Links
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Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
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- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
- G01N15/1456—Electro-optical investigation, e.g. flow cytometers without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
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- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
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- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
Definitions
- a flow cytometer adapted to both detect and treat mammalian cells, containing means for affixing a label to cellular material, removing such label, and cleaning the filter means which effectuate such removal.
- a flow cytometer which comprises means for sampling cellular material, a means for marking cells within said bodily fluid with a marker to produce marked cells, means for analyzing the cellular material, means for removing such marker from the marked cells, means for sorting the cellular material, means for modifying a portion of the cellular material, and means for maintaining a portion of the cellular material which has been analyzed in a viable state.
- Figure 1 is a flow diagram of one preferred process of the invention
- Figure 2 is a schematic of one preferred assembly of the invention for sampling, wherein the assembly is comprised of a flow cytometer;
- Figures 3A, 3B, and 3C schematically illustrate the actions of the pump of the assembly depicted in Figure 2;
- Figure 4 is a schematic diagram of one preferred means for preparing a bodily fluid for analysis;
- Figure 5 is a schematic of the detection/treatment system of the flow cytometer
- Figure 6 is a schematic of the flow cytometer assembly in relation to the location of bodily fluids
- Figure 7 is a schematic of one preferred means for maintaining a viable bodily fluid
- Figure 8 is a schematic of a flow cytometer disposed within a living body
- Figure 9 is a schematic of a flow cytometer disposed outside of a living body
- Figure 10 is a block diagram of another preferred process of this invention.
- Figure 11 is a block diagram of yet another preferred process of the invention.
- Figure 12 is a block diagram of one preferred marker remover used in the process of Figure 11.
- Figure 1 is a flow diagram of one preferred process 10 for analyzing, treating, and maintaining certain bodily fluids. Sampling
- the bodily fluids are sampled.
- the body fluids which are typically sampled, include, e.g., blood, lymph, spinal fluid, bone marrow, and the like.
- the body fluids are sampled by means of the sampling system described in United States patent 6,159,164, the entire disclosure of which is hereby incorporated by reference into this specification.
- the system of this patent samples a body fluid through a tube attached to a patient's body; and the system is operable buy a user having a hand, including a palm, a thumb, and at least a first finger and a second finger.
- the system comprises a fluid sampling site connected to the tube; means for receiving the tube; means for forming a chamber; means for selectively increasing the size of the chamber to a maximum volume and for decreasing the size of the chamber to a minimum volume, the means for increasing and decreasing the size of the chamber being operable by moving the first and second fingers or the thumb in a flexion movement toward the palm to achieve the maximum volume of the chamber, the means for increasing and decreasing the size of the chamber also being operable by moving the first and second fingers or the thumb in a flexion movement toward the palm to achieve the minimum volume of the chamber such that the same motion of the user's first and second fingers can selectively accomplish the maximum volume to aspirate fluid from the patient's body to the fluid sampling site or accomplish the minimum volume to expel the fluid into the patient's body.
- Figures 2 and 3 indicate another sampling assembly which may be used.
- Figure 2 outlines the pump's bodily location and Figure 3 details the pumping action.
- a patient has disposed within her body, beneath her diaphragm 16, a pump 18 which is actuated by the movement of diaphragm 16 in the direction of arrows 19 and 20.
- the pump 18 has a deformable and elastic casing 22.
- casing 22 When casing 22 is compressed between diaphragm 16 and abdominal wall 24, its interior volume will decrease, and fluid disposed within pump 18 will be discharged through line 26 to flow cytometer 44.
- the pump 18 comprises one-way flow valve 30, which allows flow only in the direction of arrow 32; and it also comprises one way flow valve 34, which only allows flow in the direction of arrow 36. Thus, when casing 22 is compressed, fluid only may flow through line
- the pump 18 is shown disposed beneath the patient's diaphragm 16, it will be apparent that such pump 18 may be disposed beneath or nearby other parts of a body which expand and contract. Thus, by way of illustration and not limitation, the pump 18 may be positioned between lung and ribcage, between muscle and bone, between a heart and a sternum, and the like.
- FIG. 3 A, 3B, and 3C illustrate the operation of pump 18 in its intake phase
- the pump 18 is replaced by a piezoelectric or electrostrictive assembly (not shown), which, upon pressure being applied to it, produces a difference of potential sufficient to actuate a pump to which it is electrically connected.
- the bodily fluid which has been sampled, is then prepared for analysis.
- a biological sample is contacted with two or more blood cell populations with a selective nucleic acid specific blocking agent to form a sample mixture.
- the sample mixture is then contacted with a cell membrane permeant, red- excited dye without significantly disrupting cellular integrity of the cells to form a dyed sample mixture.
- the dyed sample mixture is excited with light in a single red wavelength; and, thereafter, fluorescence emitted from different cell populations in the dyed sample mixture are measured, wherein the fluorescence emitted from one blood cell population is distinguishable from the fluorescence emitted from another blood cell population.
- the appropriate dye(s) or other markers are fed to reservoir 70 by line 72 and, in response to one or more signals from controller 64, is fed into injector 74 and thence into line 26, where the dye(s) mix with the fluid disposed within such line 26 and selectively mark them.
- the marker may be removed from the fluid by conventional means.
- the marker may be removed by means of an adsorption column 78 and/or by other adsorption means.
- the dye may be removed by other means, including chemical means.
- processes for stripping dyes or decolorizing various materials are known in the art. For example, U.S. Pat. No.
- 4,227,881 discloses a process for stripping dyes from textile fabric, which includes heating an aqueous solution of an ammonium salt, a sulfite salt and an organic sulfonate to at least 140 degrees F (60 degrees C) and adding the dyed fabric to the heated solution while maintaining the temperature of the solution.
- U.S. Pat. No. 4,783,193 discloses a process for stripping color from synthetic polymer products by contacting the colored polymer with a chemical system.
- a purified bodily fluid is returned via line 50/52 to either the body or a reservoir.
- additional material needed for such process may be charged via line 80, and/or dye and/or other waste material may be removed via line 80.
- the reservoir 70 may contain one or more markers, and/or it may contain diluent to preferably dilute the bodily fluids so that preferably only one cell passes by any particular point in flow chamber 76 at any one time.
- this "laminar flow condition" facilitates the analyses of the bodily fluid by optical means.
- the selectively marked bodily fluid(s) are then tunneled into the flow chamber 76 of the cytometer 44, wherein they are subjected to analysis by conventional optical means.
- the marked bodily fluid is analyzed.
- a light source 84 is caused to focus on flow chamber 76.
- the amount of light transmitted through flow chamber 76 will vary with the properties of the bodily fluid within such chamber; see, e.g., United States patents 6,197,756, 6,197,593, 6,197,583, 6,197,582, 6,197,568, 6,197,540, and the like. The entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.
- the light transmitted through flow chamber 76 is detected by detector 86 which may, e.g., be a photodetector. Data is fed from detector 86 to controller 88.
- Controller 88 is equipped with a database indicating the properties of normal bodily fluids. The property of any particular bodily fluid being analyzed can be compared with this database to determine whether they correlate. A lack of correlation may indicate a disease state, which can be thereafter treated by the cytometer 44.
- step 90 data is collected from the analysis conducted in controller 88. Historical data may also be fed to the data collection device, either before, during, or after the analysis 82 of the bodily fluid.
- the collection of data in step 90, and it use, may be done in accordance with United States patent 6,197,593, the entire disclosure of which is hereby incorporated by reference into this specification.
- Data from data collection step 90 may be added to from external sources. Alternatively, data from data collection step 90 may be exported to one or more external devices. In one embodiment, not shown, when analysis step 82 and data collection step 90 indicate the presence of a dangerous abnormal condition within the bodily fluid, an external alarm is activated to warn the patient. When analysis 82 of the bodily fluid indicates that it is abnormal, the bodily fluid may be charged via line 92 to treatment step 94. As is indicated in Figure 5, this treatment step 94 may occur in line within the flow chamber 76.
- injector 96 is operatively connected to both detector 86 and controller 88 and, in response to signals therefrom, feeds energy and/or material to the bodily fluid to treat it.
- One may feed radiation 98 to the bodily fluid to treat it.
- one may cause ultraviolet radiation to impact flow chamber 76 and to kill cancerous cell(s) disposed within such flow chamber 76.
- electrical discharge 100 by means such as, e.g., electroporation.
- magnetic fields 102 e.g., one may use sound particles and rays 104.
- one may feed material via line 106 into flow chamber 76, which is adapted to kill or modify the abnormal cell(s).
- there is a need to replenish material within injector 96 such material may be fed to injector 96 via line 115 from reservoir 116.
- the controller 64 can cause the close valves 112 and 114 so that fluid disposed between such valves cannot flow. Because the flow cytometer 44 is capable of detecting one cell at a time, any abnormal cell detected at point 108 may be treated at point 110, e.g., the controller 88 determining precisely where such particular cell is at any point in time.
- the cells or bodily fluid treated in step 94 may be returned to the body in step 122.
- body fluids which have been analyzed by cytometer 44, may be fed via line 50 to vessel 41, which may be the same or different from the blood vessel 40, from which the bodily fluid was sampled.
- vessel 41 which may be the same or different from the blood vessel 40, from which the bodily fluid was sampled.
- analyzed bodily fluids may be fed via line 52 to reservoir 54, which, in the embodiment depicted, is disposed in a blood vessel 56. Sorting
- the cells analyzed in step 82 may be sorted in sorting step
- this sorting step one may selectively segregate and collect certain cells within the bodily fluid.
- stem cells are sorted from the bodily fluid.
- the identification and separation of such stem cells may be conducted by conventional means such as, e.g., the means disclosed in United States patent 5,665,557, the entire disclosure of which is hereby incorporated by reference into this specification.
- quintruplicate aliquots of KGla cells 0.5 x 10 6 /analysis
- 2microliters biotinylated conjugates of 8A3, 7D1, 7C5 or 8A1 were then added to each of the 4 sets of the above samples (i.e.
- the stem cells sorted in step 118 may be collected and thereafter used for many different purposes. Maintenance
- Figure 7 is a schematic of a means for maintaining bodily fluid (and/or a portion thereof) in maintenance step 120. Referring to Figure 7, some or all of the cells, which have been sorted in sorter 118, may be passed via line 52 to reservoir 54. In one embodiment, not shown, sorter 118 is bypassed and bodily fluid is directly passed into reservoir 54.
- reservoir 54 is disposed within blood vessel 56, and which is composed of porous material.
- reservoir 54 may be disposed adjacent to a blood vessel, and/or be disposed adjacent to the intestines. This allows all necessary nutrients and supplies to be available to the retained cells. It also allows for waste products to be removed from reservoir 54.
- the porous material has a pore size that allows cells to remain within reservoir 54, but which allows nutrients and waste products to diffuse freely. Removal
- the flow cytometer 44 may be disposed either within or without the patient's body.
- a flow cytometer 44 is disposed in a patient's body.
- the flow cytometer 44 is disposed beneath a patient's skin, in the abdominal cavity.
- the flow cytometer 44 may be implanted within the patient's body by conventional means.
- one may implant flow cytometer 44 by the method disclosed in United States patent 6,198,950, the entire disclosure of which is hereby incorporated by reference into this specification.
- the implantable device is implanted under the skin in such a manner that the cannula projects into a blood vessel.
- flow cytometer 44 is disposed outside the body 14 rather than inside it.
- cytometer 44 may be removably attached to the body 14 by conventional means such as, e.g., belt 48 extending around the torso of the patient.
- the bodily fluid is sampled from, returned to or maintained in the body via cannulae tubes 26, 38, 50 or 52. Size
- the flow cytometer 44 preferably has a weight of less than 12 pounds and, more preferably, weighs less than about 6 pounds. In one embodiment, the flow cytometer 44 is made from miniaturized components and weighs less than about 3 pounds. Technologies that enable this size and weight to be achieved include low energy lasers and advanced flow chambers that allow cells to flow in a narrowly focused laminar flow stream. Power
- controller 64 is operatively connected to a power source 66.
- pump 18 provides power to power source 66.
- every output cycle of pump 18 provides some hydraulic pressure via line 68 to pump 66.
- This hydraulic pressure is converted into electrical power by conventional means such as, e.g., piezoelectric means.
- power source 66 is a battery.
- the battery may be rechargeable.
- the battery is recharged by electromagnetic radiation.
- the electromagnetic radiation may be transferred from a source disposed within the patient's body; or it may be transferred from a source external to the patient's body.
- a magnetic field may be produced by passing alternating current through a wire or coil, and this alternating magnetic field may be transmitted through a patient's skin into his body and coupled with an transducer, which produces alternating current from the alternating magnetic field.
- material and/or energy is fed to power source 66 via a line (not shown), and this material and or energy is adapted to furnish power to power source 66.
- the material charged to power source 66 may undergo and/or facilitate a reaction, which produces energy consumed by power source 66.
- the casing 22, of pump 18 is made from a flexible, elastic biocompatible material.
- the flow cytometer is made from biocompatible materials such as surgical steel or encased in biocompatible materials. All cannulae and tube are preferably made from flexible, biocompatible materials.
- Flow chamber 76 is preferably transparent to the desired light source. Bodily Fluids
- flow cytometer 44 is sampling blood.
- the flow cytometer 44 is so disposed that it samples bodily liquids such as, e.g., lymph, bone marrow, spinal fluid, and the like.
- the flow cytometer 44 is adapted to sample and analyze and treat unmodified bodily liquids, that is, bodily liquids occurring in their natural state within the body. Another preferred process of the invention
- FIG 10 is a block diagram of a preferred process 161, which utilizes element 78 (see Figure 4).
- the output of flow cytometer 44 is fed through flow chamber 76 (see Figure 4) to marker/stripper 150, wherein the marker is removed from the cellular material flowing through chamber 76.
- the marker had first been affixed to such cellular material with injector 74 (see Figure 4); this marker is discussed elsewhere in this specification.
- flow cytometry FC is used to detect variations in cell types and/or particles by use of fluorescent labeling and endogenous cellular optical properties. Originally flow cytometric systems were used solely to rapidly count cells.
- the cells were traditionally isolated from tissue or blood and labeled with fluorescent markers or antibodies conjugated with fluorescent tags. A variety of cell types have been analyzed using these methods. Cell volume and type could also be characterized by the intensity and frequency component of transmitted light. Following isolation, cells were then fed through a flow chamber of specified dimensions.
- Optical flow cytometer systems are based on either the detection of intrinsic scattering properties of cells (which include the cellular membrane structure, organelle concentration and structure, cytoplasmic structure, and DNA/chromatin structure) and/or of detection of emitted light from fluorescently labeled cells.
- the cells are usually labeled with fluorescent conjugated antibodies to cell surface receptors or cytoplasmic proteins.
- a source for the emission of a specified frequency of energy i.e., a light source
- a light source is directed toward the stream of flowing cells tlirough a narrow flow cell.
- the bodily fluid is blood, and it is caused to flow by the action of a heart.
- the bodily fluid may be a non-hematologic fluid such as, e.g., lymph, urine, cerebrospinal fluid, and the like.
- the bodily fluid is comprised of red blood cells and/or leukocytes and/or neutrophils and/or other cells or cellular material. Each of these components will have a different optical response to a specified optical input.
- the cells of the bodily fluid preferably have either endogenous optical properties, and/or they are labeled to provide optical properties.
- the cells may be labeled with fluorescently conjugated antibodies.
- the flow cytometer will utilize either injected fluorescent contrast or emitted light energies intrinsic to specific cells themselves.
- antibodies may be conjugated with polymeric dies with fluorescent emission moieties such as aminostyryl pyridinium (see, e.g., United States patent number 5,994,143, the entire disclosure of which is hereby incorporated by reference into this specification).
- the function of a flow cytometry system is to determine which, if any, of four antigens are carried by blood cells, including cell
- respective antibodies for the antigens are derivatized with respective fluorochromes allophycocyanin (APC), peridinin chlorophyl protein (PerCP), fluorescein isothiocyanate (FITC), and R-phycoerythrin (RPE).
- APC fluorochromes allophycocyanin
- PerCP peridinin chlorophyl protein
- FITC fluorescein isothiocyanate
- RPE R-phycoerythrin
- United States patent 5,994,143 discloses another process for fluorescent antibody conjugation; the entire disclosure of this United States patent is hereby incorporated by reference into this specification.
- the first of two closely positioned fluorophores may be excited by light of a given wavelength. Then, instead of emitting light of a longer wavelength, the excited fluorophore transfers energy to the second fluorophore. That transferred energy excites the second fluorophore, which then emits light of an even longer wavelength than would have been emitted by the first fluorophore.
- An example of such an energy transfer arrangement involves phycobiliprotein-cyanine dye conjugates. Subjecting these conjugates to an about 488 nm laser light excites the phycobiliprotein. The phycobiliprotein will then, without itself irradiating, transfer energy to the cyanine fluorophore at the excitation wavelength of the cyanine, which is coincident with the emission wavelength of the phycobiliprotein, about 580 nm. Consequently, the cyanine fluorophore is thereby excited and subsequently emits light of its emission wavelength of about 680 nm.
- fluorescent dyes are injected upstream of the device 44, preferably into a venous blood supply.
- the dyes may be injected in a manner similar to that used to inject contrast agents for medical ultrasound techniques. See, e.g., United States patents 6,177,062 ("Agents and methods for enhancing contrast in ultrasound imaging"), the entire disclosure of each of which is hereby incorporated by reference into this specification.
- the fluorescent dyes preferably are not toxic to the living body and care must be taken in preparation of the fluorescent dyes.
- the combination of different wavelength fluorochromes conjugated to antibodies to different cells along with the endogenous optical properties of the cells will provide a complex multiparameter data set where differing signals from different cells will be discernable.
- the bodily fluid is comprised of plasma.
- the device 44 detects the intrinsic scattering properties of cells (which are influenced by the cellular membrane structure, organelle concentration and structure, cytoplasmic structure, and DNA/chromatin structure).
- the markers or markers are removed from the bodily fluid in marker/stripper 150.
- One may use conventional means from removing the marker(s) from the bodily fluid.
- the marker may be removed by means of an adsorption column 78 and or by other adsorption means.
- the dye may be removed by other means, including chemical means.
- processes for stripping dyes or decolorizing various materials are known in the art. For example, U.S. Pat. No.
- 4,227,881 discloses a process for stripping dyes from textile fabric which includes heating an aqueous solution of an ammonium salt, a sulfite salt and an organic sulfonate to at least 140 degrees F (60 degrees C) and adding the dyed fabric to the heated solution while maintaining the temperature of the solution.
- U.S. Pat. No. 4,783,193 discloses a process for stripping color from synthetic polymer products by contacting the colored polymer with a chemical system.
- dye separators are used in maker/stripper 150, and these dye separators may require additional plasma fluid, which may be obtained from a plasma reservoir (not shown), which is connected to the dye separators.
- the removed marker(s)/dye(s) are fed via line 152 to a controllable switch valve, which can feed the marker(s)/dye(s) to one or more different locations, depending upon the nature of the marker(s)/dye(s) .
- the dyes are fed via line 80 to dye reservoir 70 (see Figure 4).
- the dye(s)/marker(s) waste material is fed to another reservoir/holding tank (not shown), to be disposed of.
- the dye(s)/marker(s) may be fed to the patient's bladder and/or gastrointestinal tract, depending upon the toxicity and/or degradability of the dye(s)/marker(s).
- the controller 64 which includes one or more suitable sensors (see Figure 4), controls to which destination(s) the dye(s)/marker(s) are to be sent.
- the purified body fluid is fed via line 156 to a fluid tester 158, which determines the degree of purity of the body fluid. If tester 158 determines that the body fluid is not purified enough, it recycles the impure fluid via line 160 to pump 162 and thence via line 164 back into marker/stripper 150. If the tester 158 determines that the body fluid is adequately purified, it is fed via lines 50/52 back into the organism (see Figure 4).
- a hermetic enclosure 163 is disposed around flow cytometer 44 (see Figure 2) to isolate the flow cytometer from any living organism in which it might be implanted.
- FIG. 11 is a flow diagram of another preferred process of the invention. Referring to
- Flow cytometer 300 is comprised of a controller/processor 302, which preferably comprises a built-in programmable logic unit (PLU) and read only memory (RAM)/read and write memory (ROM) library interface.
- the flow cytometer 300 also comprises communications means 304, which, preferably, is telemetry communications means.
- the controller 302 is preferably so constructed as to control all adjustable parameters of all adjustable sub-components of flow cytometer 300.
- the telemetry communication means 304 is preferably so constructed as to enable the controller/processing unit 302 to receive and analyze (via the programmable logic unit) data information from all the sub-components of the flow cytometer 300 particle analyzer as well as to transmit action adjustment comments to said sub-components based on said analysis of sub-component's sensed or status data. Additionally, communications (telemetry) means 304 may optionally consist of means for communicating with an external programmer, enabling the controller/processor 302's programming of the programmable logic unit (PLU) to be modified. Additionally, the communication telemetry means 304 preferably has the ability to transmit information received from all the sub-components, raw and/or analyzed results performed by the programmable logic unit to an external programmer.
- the bodily fluid stream 306 enters a bypass valve 308 which optionally may allow the bodily fluid stream 306 to continue passing through the cytometer 300 and/or may be set, via the controller 302, to divert the bodily fluid stream 306 via channel 350 around the flow cytometer 300 and back into the primary path of the bodily fluid stream 360.
- a bypass valve 308 which optionally may allow the bodily fluid stream 306 to continue passing through the cytometer 300 and/or may be set, via the controller 302, to divert the bodily fluid stream 306 via channel 350 around the flow cytometer 300 and back into the primary path of the bodily fluid stream 360.
- the blood stream 306 may enter one-way flow valve 310 and/or one-way flow valve 330.
- These one way flow valves 310/330 ensure that no fluids nor any chemical additives dissolved in the fluids nor any foreign particles may move upstream of the flow valves 310 and 330, either by diffusion or by any other means.
- the blood stream fluid is mixed with marker(s)/dye(s) from dye reservoir 314.
- Dye reservoir 314 may consist of several dyes either in individual chambers or mixed together into a single chamber. Alternatively, dye reservoir 314 may consist of a single dye.
- controller controls the control of the dye(s) injection into the mixing chamber 312 to the mixing chamber 312 effected by controller
- the dye reservoir contents may be monitored by said controller 302. If the reservoir 314 is empty of a dye, the patient or external programmer may be notified by communication means 304.
- the mixed blood fluid and dye enter the detection and/or sorting sub-component 316 (see Figure 4 and, in particular, element 76; also see Figure 5 and element 76). If the blood is to be sorted, the sorted fluid is channeled to a dye separator 324 and then stored into sorted reservoir 326 for future extraction and/or other utilization. That portion of the blood fluid and dye marker mix, which is not sorted, is preferably fed to dye separator 320.
- the functionality of the dye separators 320, 324 may require additional plasma fluid, which may be obtained from plasma reservoir 334, which is connected to the dye separators
- the fluid is returned to the blood stream 360.
- the by-pass valve 308 it may enter the one-way flow valve 330.
- the blood On passing through the one-way valve 330, the blood enters a plasma fluid separator
- Said plasma separator 332 filters and directs a portion of the plasma fluid into plasma reservoir 334 for latter use, as described above. That portion of the fluid, which is not diverted to the plasma reservoir 334, is returned to the blood stream 360 through channel 352.
- FIG 12 is a block diagram of one preferred dye separation means, which may be used in the process of Figure 11.
- dye separator 400 is illustrated.
- a blood/dye mixture enters the dye stripper 400 through connector 402 and passes into a control valve 404.
- the control valve 404 may direct the blood/dye mix to either dye stripper 406 or dye stripper 414. This allows one of the dye separators 406, 414 to process the fluid while the other dye separator is performing an alternate function, e.g. self-diagnostics, and or cleaning of filters and/or other maintenance functions.
- control valve 404 as well as the dye strippers 406, 414 are controlled by the controller 302.
- the blood fluid dye mix e.g., is directed to dye stripper 406.
- the waste material, dye, or other stripped or filtered waste is directed to control valve 408, which may direct the stripped dye via channel 410 back to the dye reservoir 314 of
- Figure 11 may direct said material, e.g. to the bladder or other locations via channel 412.
- the blood fluid which has been stripped of dye material, is passed from the dye stripper
- tester 422 which is used to verify that all the dye has been remove from the blood fluid.
- the blood fluid is directed back into the dye separator 400 via connections 424 and 402.
- the tester 422 determines that the blood fluid is safe to return to the blood stream, then the blood fluid is passed to the blood stream 440.
- the controller 404 may direct the blood/dye mix to enter dye stripper 414 rather than dye stripper 406.
- the functionality of sub-components 414, 416, 418, 420, 432 are the same as described for sub-components 406, 408, 412, 410, 430 respectively.
- the dye strippers 406, 414 of Figure 12 may be placed into a diagnostic and cleaning mode, hi this mode, filters and or surfaces, not shown, of the dye strippers 406, 414, may be cleansed by a variety of methods including, but not limited to, chemical means, electromagnetic means, heat, mechanical means, cross-fluid flow, back-fluid flow, or other means. Such cleaning methods may require additional fluids. This is provided for by the plasma reservoir 334 of Figure 11, which is connected to the dye stripper 406, 414 of Figure 12, via connections 430, 432, respectively, of Figure 11.
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US09/918,078 US6743190B2 (en) | 2001-05-07 | 2001-07-30 | Flow cytometer shunt |
US09/918,078 | 2001-07-30 |
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WO2003011385A1 true WO2003011385A1 (en) | 2003-02-13 |
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PCT/US2002/023780 WO2003011385A1 (en) | 2001-07-30 | 2002-07-29 | Flow cytometer shunt |
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US8647292B2 (en) | 2007-08-17 | 2014-02-11 | The Invention Science Fund I, Llc | Systems, devices, and methods including catheters having components that are actively controllable between two or more wettability states |
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US8162924B2 (en) | 2007-08-17 | 2012-04-24 | The Invention Science Fund I, Llc | System, devices, and methods including actively-controllable superoxide water generating systems |
US8702640B2 (en) | 2007-08-17 | 2014-04-22 | The Invention Science Fund I, Llc | System, devices, and methods including catheters configured to monitor and inhibit biofilm formation |
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