Magnetic Filtering Device and Method

Abstract

A blood filtration system. In one embodiment, the blood filtration system includes: a container having a first surface, a second surface, and one or more wall surfaces that define a volume; an input port in fluid communication with the first surface; an output port in fluid communication with the second surface; a filter bed including a plurality of planar magnetic meshes stacked in a closely juxtaposed manner and positioned within the volume of the container and coplanar with the first and second surfaces; a first magnet positioned on the first surface of the container; a second magnet positioned on the second surface of the container; a first input conduit in fluid communication with the input port; and a first output conduit in fluid communication with the output port. In another embodiment, the blood filtration system includes a pump in the input conduit.

Description

Technical Field

[0001] The present invention generally relates to blood filtration systems, and more particularly to magnetic filtration systems. Background Art

[0002] Magnetic separation has been used in mineral processing for many years. Generally, magnetic separation is used to separate magnetic minerals from a mixture containing non-magnetic materials. In such a separation system, a suspension of particles in a liquid passes through a magnetizable filter constructed of magnetic wires. Near the wire, a high field gradient induces a magnetic holding force that attracts any magnetizable material passing through.

[0003] These magnetic separation techniques can be used with magnetic blood filters to remove any substance that is inherently magnetic (i.e., significantly deviates from the diamagnetism of normal blood and blood components) or magnetically labeled with magnetic nanoparticles or beads that target specific blood-borne agents that are accessible and clinically useful from the bloodstream.

[0004] What is needed is a magnetic filter that can extract magnetically labeled targets in the bloodstream quickly, efficiently, and at low cost.

[0005] The present invention meets these requirements. Summary of the Invention

[0006] One aspect of the present invention is a blood filtration system. In one embodiment, the blood filtration system includes: a container having a first surface, a second surface, and one or more wall surfaces that define a volume; an input port in fluid communication with the first surface; an output port in fluid communication with the second surface; a filter bed including a plurality of planar magnetic meshes that are stacked in a closely juxtaposed manner and positioned within the volume of the container in the fluid path from the input port to the output port; a first magnet positioned on the first surface of the container; a first input pipe in fluid communication with the input port; and a first output pipe in fluid communication with the output port, wherein the first magnet generates a magnetic field that is modified by the presence of the planar magnetic meshes so as to generate a sufficiently strong and non-uniform magnetic field in the free space within the filter bed to allow capture of blood-borne magnetic targets. In another embodiment, a second magnet is positioned on the second surface of the container.

[0007] In yet another embodiment, the blood filtration system includes a pump in the input conduit. In still another embodiment, the blood filtration system includes a saline drip unit in fluid communication with the input conduit. In yet another embodiment, the blood filtration system includes a saline reservoir and an infusion pump that is connected to a first conduit in parallel fluid communication via a T-joint. In still another embodiment, the blood filtration system includes an air detector in fluid communication with the output conduit. In one embodiment, the blood filtration system includes a pressure detector in fluid communication with the output conduit.

[0008] In another aspect, the present invention is a blood filter that includes: a container having a first surface, a second surface, and one or more wall surfaces that define a volume; an input port in fluid communication with the first surface; an output port in fluid communication with the second surface; a filter bed that includes a plurality of planar magnetic meshes stacked in a closely juxtaposed manner and positioned within the volume of the container and coplanar with the first and second surfaces; a first magnet positioned on the first surface of the container; a second magnet positioned on the second surface of the container; wherein the first and second magnets generate a magnetic field that is perpendicular to the planar magnetic meshes and creates a sufficiently strong and non-uniform magnetic field in the free space within the filter bed to allow for the capture of blood-borne magnetic targets.

[0009] In yet another embodiment, the filter is designed to produce a uniform flow characteristic of millimeter scale length to avoid dead spots and vortices, and to maintain an overall sufficient flow rate by creating a complex laminar flow path for each individual red blood cell passing through the filter. In one embodiment, the flow causes the red blood cells to deviate from an unobstructed flow by more than three times the diameter of the red blood cell. In another embodiment, the deviation from the unobstructed flow is about 20 microns or more.

[0010] Typically, a blood filter is designed to create a three-dimensional braided laminar flow on a portion of the blood passing through the filter. In this regard, the flow of blood is like a meandering riverbed, but through a three-dimensional volume rather than on a two-dimensional surface. In one embodiment, a stack of planar wire meshes is arranged such that the blood passing through the filter is separated into a series of laminar flow channels as it moves through each layer of the mesh, and these laminar flow channels continuously separate and recombine. The laminarity of the flow is maintained throughout the entire portion of the stacked meshes filled within the filter, such that there is no violent or potentially destructive turbulent motion during the passage of the blood. At the same time, the continuous separation and recombination of the laminar flow channels ensure that each portion of the blood - such as, for example, a given individual red blood cell or a magnetically labeled biomolecule - has a finite, non-zero probability of physically encountering at least one capture site (defined as a spatial volume sufficiently close to the magnetically actuated mesh), and for a magnetic or magnetically labeled entity moving at an expected speed and having expected magnetic characteristics, the entity will be captured (held and retained) as it passes through the portion of the filter filled with the stacked meshes.

[0011] In one embodiment, a multi-layer stack of wire-type meshes is arranged such that the laminar flow channels into which the blood separates as it passes through the portion of the filter filled with the stacked meshes are highly regularized, such that the three-dimensional pattern of the separation and recombination of the flow channels will adopt a regular, well-defined structure. This embodiment is achieved by arranging the mesh layers in a repetitive, ordered, and aligned pattern in space.

[0012] In another embodiment in this aspect of the blood filter, a multi-layer stack of wire-type meshes is arranged such that the laminar flow channels into which the blood separates as it passes through the portion of the filter filled with the stacked meshes are more arbitrary, random, or swirling, such that the three-dimensional pattern of the separation and recombination of the flow channels will adopt an irregular, arbitrary structure. This embodiment is achieved by arranging the mesh layers in a non-aligned, arbitrary pattern in space.

[0013] In another aspect, the blood filter is designed such that the Reynolds number of the blood passing through the region of the filter filled with the stacked meshes is a typical Reynolds number for laminar flow, rather than a Reynolds number for turbulent or transitional (meaning intermediate between laminar and turbulent) flow. The Reynolds number can be defined in several ways, and two of these ways are described herein for illustrative purposes, and the operator should apply the appropriate definition to the embodiment of the blood filter being used. In the first case, the Reynolds number is defined as Re = ρvL / μ, where ρ is the density of the blood (about 1.06×10 3 kg m ～3), where v is the average velocity of the blood as it passes through the filter, L is the characteristic size of the filter, such as the size of the mesh pores, and μ is the viscosity of the blood (about 3 - 4×10 ～3 Pa s). In this case, for laminar flow, Re is less than 2300 or about 2300. In the second case, the Reynolds number is defined for any packed bed of hard spheres, Re* = p u d / μ(1 - ε), where p and μ are as defined previously, u is the superficial flow rate of the blood through the filter (given by dividing the volumetric flow rate through the filter by the macroscopic cross-sectional area of the filter), d is the diameter of the spherical equivalent particle (i.e., the diameter of the sphere that would occupy the same volume of space as the given filter mesh material), and ε is the bed porosity (meaning the fraction of the volume of the filter that is not occupied by the filter material). In this case, for laminar flow, Re* is less than or about 10.

[0014] In yet another aspect, the blood filter is designed to provide efficient capture at flow rates and filtration volumes comparable to the flow rates of blood arriving at and leaving the arteries or veins of the human body, and to provide an acceptable safety limit for the amount of blood that can be retained outside the body at any given time. For children, this corresponds to flow rates from 40 to 200 ml / min, and an extracorporeal volume of about 8% of the total blood volume, e.g., for a 5-year-old child weighing 20 Kg it would be 0.08×1.6 liters = 128 ml. In adults, this corresponds to flow rates from 40 to 400 ml / min, and an extracorporeal volume of about 8% of the total blood volume, e.g., for an adult weighing 80 Kg it would be 0.08×6.4 liters = 512 ml.

[0015] In yet another aspect, the blood filter is designed to contain a stationary capture zone for holding and safely collecting fragile or difficult biological entities. This aspect requires that the capture zone be essentially active with respect to the flow - otherwise they would constitute "dead zones" through which the blood could not pass - while also being suitable as a receptacle for the targeted and captured biological entities. In one embodiment, these stationary capture zones are located along the length of opposite sides of the filaments, magnetized perpendicular to the orientation of the filaments and parallel to the direction of flow, creating regions of high magnetic force and low drag force, facilitating capture. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The structure and function of the present invention can be best understood from the description herein in conjunction with the accompanying drawings. These drawings are not necessarily to scale; rather, emphasis is generally placed on illustrative principles. These drawings are considered illustrative in all respects and are not intended to limit the present invention, the scope of which is defined only by the claims.

[0017] Figure 1 is a block diagram of an embodiment of the system of the present invention;

[0018] Figure 2 is a perspective view of a magnetic filter housing;

[0019] Figure 3A is Figure 2 a side view of an embodiment of the magnetic filter housing shown in

[0020] Figure 3B is Figure 2 a bottom view of an embodiment of the magnetic filter housing shown in

[0021] Figure 3C is Figure 2 a cross-sectional view of a flow conditioner of an embodiment of the magnetic filter housing shown in

[0022] Figure 3D is Figure 3C a top view of a flow conditioner of an embodiment of the magnetic filter housing shown in

[0023] Figure 4A is Figure 2 a sectional view of an embodiment of the magnetic filter housing shown in

[0024] Figure 4B is Figure 4A a sectional view of an embodiment of the magnetic filter housing shown in through line DD';

[0025] Figure 5A is a perspective view of an embodiment of the mesh layer of a five-layer magnetic mesh filter;

[0026] Figure 5B is Figure 5A a top view of a part of the five-layer filter of , which is enlarged to show the staggered arrangement of the wires;

[0027] Figure 5C is a graph of the effect of the ratio of the wire diameter to the lateral length of the holes on the drag force on fluid flow;

[0028] Figure 6A is a top view of an embodiment of the mesh of a magnetic filter in a Dutch weave configuration;

[0029] Figure 6B is a side view of an embodiment of the mesh of a magnetic filter in a flat Dutch weave configuration;

[0030] Figure 6C is Figure 6B a perspective view of an embodiment of the mesh of the magnetic filter of ;

[0031] Figure 6D Top view of an embodiment of the mesh of a magnetic filter in a flat configuration or a woven configuration one on top of the other;

[0032] Figure 6E Top view of an embodiment of the mesh of a magnetic filter in a flat configuration or a woven configuration one on top of the other, wherein the spacing between the wires is different in each direction;

[0033] Figure 6F Top view of an embodiment of the mesh of a magnetic filter in a twill configuration or a woven configuration two on top and two on the bottom;

[0034] Figure 7 Block diagram showing an embodiment of a filter housing positioned near a magnet;

[0035] Figure 8 Block diagram of an embodiment of a dual-magnet assembly with a steel armature;

[0036] Figure 9 Field map of the magnetic field near a cylindrical wire, the cylindrical axis of which is perpendicular to the externally applied field;

[0037] Figure 10 Shows a stationary capture zone near the wire in a magnetic field;

[0038] Figure 11 Block diagram of an embodiment of a six-magnet magnetic assembly with a steel backplate and aluminum supports;

[0039] Figure 12 Perspective view of an embodiment of the upper and lower magnetic assemblies acting as magnets for the present invention;

[0040] Figure 13 Graph showing the ratio of parasite reduction to filtered volume. DETAILED DESCRIPTION

[0041] Referring Figure 1 , system 10 constructed in accordance with an embodiment of the present invention includes an input port 14 and an output port 18. In one embodiment, the input port 14 and output port 18 include Luer-type connectors configured to engage corresponding mating Luer-type connectors of a patient's fluid conduit. Blood from the patient is drawn into system 10 through input port 14 using a pump 22 connected to input tubing 25. In one embodiment, the pump is a peristaltic pump. Also included at the other end of the input line is a Luer-type connector 30 positioned to engage a corresponding mating Luer-type connector 32 of an input port 26 of a magnetic filter 34 configured as such.

[0042] The luer fitting at the output port 38 of the magnetic filter 34 engages the luer fitting 36 at one end of the output conduit 42 of the system. The other end of the system output conduit 42 includes a luer fitting that serves as the system output port 18. The luer output port engages a catheter that returns blood to the patient. In one embodiment, the peristaltic pump 22 is an infusion pump (infusion pump model BM-11 from Baxter International, Deerfield, IL) and includes an output circuit that includes a gas collector 43 with a filter and an air detector 46 to detect and / or filter air bubbles in the blood stream (arrow). In this embodiment, the peristaltic pump includes a pressure sensor 48 in the output circuit to ensure that the pressure of the blood flowing back to the patient is within the desired limits. Also in this embodiment, the output circuit includes an emergency clamp 47 that can stop the flow through the circuit if a bubble is detected. In various embodiments, the input conduit 25 and the output conduit 42 are constructed of air-permeable tubing. In one embodiment, the output conduit 42 is attached to a collection receptacle 74. In another embodiment, the output conduit 42 is connected to a cannula 77 to return the patient's blood to the patient.

[0043] In one embodiment, the controller 73 controls the syringe pump 64 and the peristaltic pump 22 via a digital port 61.

[0044] In another embodiment, the saline drip subsystem 54 is connected to the input line 25 through a luer fitting 63 via a first T-connector 50. In one embodiment, the saline drip subsystem 54 includes a saline storage drip bag 62 with a manual IV line control valve 65. The input line 26 is connected to the input of the peristaltic pump 22 via a second T-connector 67. The second port of the second T-connector 67 is connected to an input pressure sensor 69 to measure the fluid pressure at the input line 25 before the pump 22.

[0045] The output of the peristaltic pump 22 is connected to a syringe pump 64 with a syringe pump driver 66 that controls the flow of an anticoagulant such as heparin from a syringe 70 through a third T-connector 74. The output end 78 of the third T-connector 74 is the second input to the input conduit 26. The anticoagulant subsystem ensures that the patient's blood does not clot as the patient's blood passes through the system 10.

[0046] More specifically, and referring to Figure 2 and Figures 3A to 3D, the magnetic filter 34 includes an outer container 82. In one embodiment, the outer container 82 is made of disposable plastic or a sterilizable material. In one embodiment, the plastic is a medical-grade plastic such as polyethylene, polycarbonate, or silicone. In one embodiment, the inner surface of the container and the mesh are coated with an anticoagulant. In one embodiment, the anticoagulant coating is a complex polysaccharide with heparin embedded therein. The outer container 82 is typically permanently sealed by a top cap 83 and a bottom cap 85, but the outer container can be configured to be openable for cleaning and refurbishment. The size of the housing of the container 82 is determined in part by the body size of the patient to whom the system is connected. If the volume of the filter is too large, the patient will experience a reaction due to excessive blood loss. If the volume is too small, the amount of time required to move most of the patient's blood through the device is excessive.

[0047] Typically, in nephrology, the maximum amount of blood withdrawn from a patient in an extracorporeal circuit is 8% of the patient's blood volume. The average adult has approximately five liters of blood, so the amount of blood in the extracorporeal circuit should be less than approximately 400 ml. Taking into account the fact that some patients will be anemic and reducing this amount of blood by a further 50%, the volume of the extracorporeal circuit becomes approximately 200 ml. For children, this volume must be reduced. For infants under 12 months of age, the volume of the system is approximately 30 ml. Assuming that the tubing and connectors of the system contain approximately 10 ml of blood, this means that the housing volume will vary from approximately 20 ml for an infant to approximately 190 ml for an adult.

[0048] Since the outer container 82 includes a magnetic metal mesh filter that occupies one-third of the container volume, the actual container volume is approximately one-third larger than the desired blood volume. Thus, a chamber sized for an adult (approximately 190 ml of blood) is approximately 250 ml in volume.

[0049] The shape of the container is designed to increase the flow rate through the container by reducing the drag force. To reduce the drag force, the container is constructed to have a pair of surfaces, such as the top and bottom, that have a larger surface area compared to the other (in this embodiment, four) surfaces of the container. Note that in this discussion, the filter is described as a rectangular parallelepiped, but without loss of generality, other shapes including cylindrical are contemplated. In one embodiment, the flow of blood is then directed vertically between the two larger surfaces. For example, if a volume of 125 ml is desired, it is advantageous to construct the container to have dimensions of 12.5 cm × 10 cm × 1 cm rather than constructing it such that each edge of the six surfaces is 5 cm (5 cm × 5 cm × 5 cm), so that the top and bottom surfaces are 125 cm 2 . In the first case (each edge of each surface is 5 cm), the largest surface area is 25 cm 2。In a second example, the area of the largest surfaces (top and bottom) is 125 cm 2 。Since the linear velocity of a liquid for a given volumetric flow rate depends on the area of the surface through which the liquid flows, maximizing the surface area minimizes the linear flow velocity and thus minimizes the drag force. Thus, for flow between the two largest surfaces, the drag force will be reduced by one fifth. However, it is important to note that increasing one side at the expense of the other will reduce the height of the filter bed.

[0050] To take advantage of the increased surface area, it is necessary to divert the incoming blood flow so that the incoming blood flow spreads out over the larger surface. Referring again to Figures 3A to 3D , the input port 26 of the container provides the blood flow through the flow equalizer or diffuser 80. As the blood travels down the tube 80 ( Figure 3C ), the tube becomes wider and flatter so that the blood spreads out over the surface as it fills the volume and ultimately reaches the output port 38. In some embodiments, the blood flows through a flow equalizer or splitter before leaving the output port 38 in order to maintain flow uniformity at the top of the chamber. Other forms of splitters or flow equalizers are feasible. It should be noted that although the system is generally described with the input port 26 at the bottom and the output port 38 at the top, the orientation of the container is not relevant, but the efficiency is increased if the volume of the blood flow is between the two largest surfaces.

[0051] One problem with a container having orthogonal walls is that the corners where the walls meet form "dead spaces" where fluid is collected and cannot flow with the majority of the flow through the container. In some embodiments, these dead spaces are removed by forming a continuous non-orthogonal surface at the meeting of the walls at the corners of the container ( Figure 3B ). In one embodiment, the inner surface of the container is coated with a hydrophobic coating. In one embodiment, the hydrophobic coating is a silicone-based polymer such as polydimethylsiloxane.

[0052] Referring to Figure 5A 、 Figure 5B, within the container 82 is a filter bed through which the blood flowing to the output port 38 passes as it enters the container 82. In one embodiment, the filter bed is constructed as a plurality of planar meshes 100, 100'... 100" (generally 100) stacked together. In one embodiment, the planes of the meshes are preferably perpendicular to the blood flow through the container volume. The mesh is constructed of non-magnetic wires 104'... 104" (generally 104) (including but not limited to iron wire or strands of iron wire), and the non-magnetic wires are woven such that the pore spacing (generally 108) between the wires is 10 - 1000 microns, and preferably 50 microns. In one embodiment, the non-magnetic wire is SS430 stainless steel having a wire diameter of 10 - 1000 microns and preferably 250 microns. In one embodiment, such a construction of at least one hundred layers of mesh corresponds to a thickness of approximately thirty mm. The stacked meshes 100, each mesh being arbitrarily offset from the previous layer such that the spacing between the wires of each mesh is staggered to form an interrupted (irregular) passage through the filter bed ( Figure 5B ). Thus, the blood cells flowing through the filter bed are highly likely to encounter multiple wires as they flow through the passage. As described below, due to the higher magnetic field in the free space adjacent to the wires, magnetic or magnetically labeled components within the blood flow experience a magnetic drag force component that slows down the flow. Figure 5C is a graph of the effect of the ratio of the wire diameter to the lateral length of the pore on the drag force. That is, when the wire diameter becomes larger relative to the side of the pore, the drag force increases sharply due to the decrease in the pore size.

[0053] Referring to Figures 6A to 6F , the magnetic mesh filter can take many forms or weaves; several embodiments are described herein. Figure 6A is an embodiment of a magnetic mesh filter in a Dutch weave construction. In a Dutch weave, the "warp" wires and "weft" wires have different diameters. Figure 6B is a side view of an embodiment of the mesh of a magnetic filter in a Dutch weave construction, Figure 6C is Figure 6B a perspective top view of the mesh of the same magnetic filter. Figure 6D is a top view of the mesh of a magnetic filter in a flat or one - on - top - of - another weave construction. Figure 6E is Figure 6D an embodiment of the mesh of a magnetic filter in which the spacing between the wires is different in each direction. Figure 6FAn embodiment of the mesh of a magnetic filter in a twill weave configuration. Generally, a weave is selected such that the area (regions, areas) of substantially maximized magnetic drag force overlaps with the area of substantially minimized viscoelastic drag force, as discussed below.

[0054] Referring Figure 7 , to establish a suitable magnetic field in the mesh, in one embodiment, a container 82 containing the mesh filter is placed near a permanent magnet 120. In a second embodiment Figure 8 , to enhance the magnetic field, two permanent magnets 120, 120' oriented in the same polarity are applied to opposite sides of the container 82 such that the magnetic field 124 is perpendicular to the plane of the mesh 100. This embodiment includes an armature 126 to provide a return path for the magnetic field.

[0055] This configuration causes the magnetic fields acting on each of the wires 100 and 104 forming each hole 108 in the mesh to be approximately equal. However, assuming the mesh is made of a ferromagnetic or ferrimagnetic material that is inherently magnetizable (inducing an induced magnetization within the wires), the magnetic field acting within each hole 108 in the mesh is modified to become a superposition of fields due to the permanent magnets 120 and 120', and the magnetic fields generated by the magnetized wires 100, 100', 100", etc. and 104, 104', 104", etc. The field due to the magnetized wires approximately has a magnetic dipole, and thus is maximized in the direction of the magnetization field and drops sharply (reduced to 1 / r 3 , where r is the distance from the wire) ( Figure 9 ). The first pair of dotted arrows extends from the top of the left - hand legend in the figure and points to high - field values (about 0.6 Tesla) in the direction of the magnetic field as shown near the top and bottom of the cross - section of the wire. The second pair of arrows extends from the bottom of the legend and points to low - field values (close to zero) on the left and right sides of the cross - section of the wire. Solid arrows and another dotted arrow are also included to emphasize two additional points in the field (about 0.15 Tesla and about 0.48 Tesla) for further elaboration of the legend. The overall magnetic field is thus strongest and has the highest field gradient in the vicinity of each wire. If a fluid containing magnetic targets then passes through the mesh of the filter such that the flow direction is parallel to the direction of the magnetization field, then as Figure 10 shown, a maximized magnetic capture zone is created near each wire of the mesh, which is characterized as a zone that combines a relatively large magnetic drag force with a relatively small viscoelastic drag force.

[0056] The magnetic force (F m ) experienced by magnetic particles passing near the wires of the mesh is given by:

[0057]

[0058] where μ 0 is the permeability of free space, χ is the volume magnetic susceptibility of the magnetic material, V is the volume of the magnetic material in particulate form, H is the magnetic field of the adjacent wire (χVH is the total magnetic moment M of the particle), is the magnetic field gradient near each wire, and boldface indicates a vector. For wires closer to the mesh, the magnetic field gradient increases.

[0059] Similarly, the drag force (F d ) exerted on a spherical object in a liquid flow is described by Stokes' law, and this drag force closely approximates the drag force experienced by magnetized and / or magnetizable entities to be captured by the filter:

[0060] F d = 6πμRν

[0061] where μ is the viscosity of the liquid, R is the radius of the cell, and v is the velocity of the liquid relative to the cell. The velocity v of the liquid applying the force on the particle depends on the volumetric flow rate f (ml / min) and the cross-sectional flow area C, and is given by:

[0062]

[0063] Since the cross-sectional area of the filter chamber is reduced by the amount of space occupied by the wires of the mesh, the actual cross-sectional area of the filter is reduced, and thus the flow rate of the liquid and hence the drag force F d depends on γ, where γ is the fractional change in area, and γ in turn depends on x, where x is the ratio of the diameter d of each wire in the mesh to the length l of one side of the pore,

[0064]

[0065]

[0066] If the wire diameter is 1 / 5 of the lateral length of the pore, the cross-sectional area of the filter is reduced to 70%, and the flow rate is reduced to 44%. The effect of the ratio x on the drag force is shown in Figure 5C .

[0067] For capture to occur, the drag force F d must be less than the magnetic force F m . To ensure compliance with this relationship, the following options can be used in the design and deployment of the device. The magnetic field H can be enhanced by changing the type and configuration of the permanent magnet or electromagnet creating the external field to increase the magnetic force (discussed below). Alternatively, the magnetic field gradient It can be changed or optimized as follows: optimizing the magnitude of H for the particular dimensions and magnetic properties of the wire; using a ferromagnetic mesh with a higher magnetic susceptibility or a higher magnetic saturation; or optimizing the diameter of the wire consistent with the magnetic field. The capture of specific targets such as magnetic particles can be improved by increasing the volume of the magnetic material of the target or by using a material with a higher magnetic susceptibility to increase the magnetic moment of the magnetic particles.

[0068] In addition, the possibility of the target passing through the region of high field gradient can be increased. In the case where the target flows through the pores of the mesh, the magnetic force is minimized at the center of the pore. Using a design of an arbitrarily stacked mesh with a large number of layers ensures that the probability that the target never passes through the high gradient region (i.e., near the surface of the wire) is very low. Additionally, reducing the drag force can also be accomplished by the following: reducing the velocity of the target (which may be undesirable as it will increase the overall processing time); increasing the cross-sectional flow area (which may also be undesirable as it is limited by the total volume of blood that can be removed from the patient in the extracorporeal loop (usually 8% of the TBV)); or using a mesh with a higher ratio of pore size to wire diameter (i.e., a smaller x). The last option must be balanced to ensure that the pores are small enough so that a sufficient number of targets can pass through to approach the wire, because large pores can create a flow path through the channel in which the particles never enter the region of high magnetic gradient.

[0069] Due to the cost and difficulty of producing and handling large magnets and in order to obtain a favorable magnetic circuit design, in one embodiment ( Figure 11 ), a plurality of smaller magnets 120 are assembled together before being placed on opposite sides of the container 82. In one embodiment, pairs of magnets 120 are magnetically or otherwise attached to a steel backplate 134 that extends a short distance beyond the magnets 120. The steel backplate 134 helps to focus the magnetic field and shield the adjacent region of the filter. The steel backplate 134 then rests on an edge 138 in a first portion 142 of the frame. The second portion 146 of the frame has a plurality of openings sized and shaped to allow the magnets 130 to project through the frame 146 and still remain aligned. The first portion 142 and the second portion 146 of the aluminum frame are bolted together 160 ( Figure 12 ) to form a magnet assembly, and the magnet assembly together with a second magnet assembly are two magnets 120, 120' positioned on opposite surfaces of the container 82. In this way, the container 82 can be removed between the magnet assemblies 160 and replaced for use by another patient.

[0070] In one embodiment, the magnet is an N42 grade NdFeB (neodymium iron boron) with a pulling force of 32.2 Kg, a surface flux density of 3,000 gauss, and a maximum magnetic energy product BH of 40 - 43 Oe. The magnet 130 is strong enough to generate a force of 45 N at a spacing of 30 mm between a pair of magnets and a force of 200 N at a spacing of 10 mm.

[0071] How to clinically use the system to remove harmful material from the blood is partly determined by the nature of the material to be removed. Materials that are not diamagnetic per se - such as malaria-infected red blood cells that are essentially paramagnetic (due to the presence of malarial pigment - a paramagnetic mineral byproduct of the parasite's hemoglobin metabolism) - can be directly removed by passing the cells through the magnetic filter 34. These targets such as viruses, bacteria, or other toxins can be removed by labeling diamagnetic targets with non-antidiamagnetic entities such as, for example, appropriately surface-functionalized ferromagnetic or ferrimagnetic nanoparticles. The principle is, for example, to coat magnetic nanoparticles with appropriate entities such as antibodies or antibody fragments or appropriate ligands, for which the corresponding antigen or receptor is present on the surface of the target entity in a certain abundance. Under favorable conditions and with appropriately designed selective targeting, the surface-functionalized magnetic nanoparticles can then be mixed with the patient's blood - for example, by injecting the functionalized nanoparticles into the patient's bloodstream or into an extracorporeal loop at a location upstream of the magnetic filter 34 - thereby magnetically labeling the targets and subsequently removing these entities by passing these entities through the magnetic filter 34.

[0072] In operation, a catheter is placed within a patient's blood vessel, and the luer-type or other connector of the catheter is connected to the luer-type connector 14 of the input conduit 25. In one embodiment, the catheter has: an input lumen that is connected to the input conduit 25 of the system 10; and an output lumen that is connected to the output conduit 42 of the system 10. The input conduit 25 draws blood from the input lumen of the catheter upstream of blood drainage, and the blood is returned through the output lumen of the catheter from the output conduit 42. In another embodiment, the input conduit of the system is connected to a single-lumen catheter, and the output conduit is connected to a second single-lumen catheter. Then the two catheters can be introduced into different veins or arteries of the patient.

[0073] More specifically, the pump 22 in the input conduit 26 draws blood from the patient and passes the blood through the magnetic filter 34. The saline drip 62 is mixed with heparin from the infusion pump 64 and mixed with the blood flowing through the input conduit 25. Once the blood passes through the filter 34, the blood is pumped through the output conduit 42 to return to the patient through another lumen of the catheter in the patient's blood vessel or through another catheter.

[0074] The air detector 46 ensures that there are no air bubbles in the blood stream returning to the patient. An air bubble removal device 43 may be included to remove any bubbles from the blood stream. In one embodiment, the air bubble removal is achieved by using a gas permeable plastic tube through the blood circuit.

[0075] Figure 13 It is a graph calculated from a model of the total filtered blood for removing blood cells infected with parasites such as malaria from the blood, assuming 90% one-way efficiency, 2% initial parasitemia load, and a total blood volume of 5 L. As shown in this graph, using simple filtration with this system can remove or reduce bacteria, viruses, parasites, or toxins loaded on the patient. This is especially important in areas where it is difficult to obtain drugs for treating infections.

[0076] Numerous embodiments have been described. Nevertheless, it should be understood that various modifications can be made without departing from the spirit and scope of the present disclosure. For example, various processes shown above can be used, reordering steps, adding or removing steps. Accordingly, other embodiments are within the scope of the appended claims.

[0077] The embodiments shown herein are intended to illustrate potential and specific embodiments of the present disclosure. These embodiments are mainly intended to explain the purpose of the present invention to those skilled in the art. One or more specific aspects of these embodiments are not intended to limit the scope of the present invention. The drawings and descriptions of the present invention have been simplified to illustrate the elements relevant to and clearly understand the present invention, while other elements have been omitted for clarity purposes. However, those of ordinary skill in the art can recognize that a slightly more focused discussion of other elements is not conducive to a better understanding of the present disclosure, and therefore, a more detailed description of such elements is not provided herein.

[0078] The processes associated with this embodiment can be executed by programmable equipment such as a computer. Software or other instruction sets that can be employed to cause the programmable equipment to execute the processes can be stored in any storage device such as, for example, a computer system (non-volatile) memory, a compact disc, a magnetic tape, or a magnetic disk. In addition, some of the processes can be programmed when the computer system is manufactured or programmed via a computer-readable storage medium.

[0079] Although the present disclosure contains many details, these details should not be construed as limiting the scope of the present disclosure or the scope that may be claimed, but rather as a description of specific embodiments of the present disclosure. Certain features described in the context of separate embodiments in the present disclosure may also be provided in combination in a single embodiment. Conversely, the various features described in the context of a single embodiment may also be provided separately or in any suitable sub-combination in multiple embodiments. In addition, although the features may be described above as acting in certain combinations and even initially claimed as such, one or more features from the claimed combination may in some cases be deleted from the combination, and the claimed combination may be intended to be a sub-combination or a variation of a sub-combination.

[0080] Similarly, although the operations are depicted in the drawings in a particular order, this should not be construed as requiring that the operations be performed in the particular order shown or in a sequential order, or that all of the operations shown be performed to achieve the desired result. In some cases, multitasking and parallel processing may be advantageous. In addition, the separation of the various system components in the above-described embodiments should not be construed as requiring such separation in all embodiments, and it should be understood that the described components and systems can generally be integrated together in a single product.

[0081] Aspects, embodiments, features, and examples of the present disclosure are considered illustrative in all respects and are not intended to limit the present disclosure, the scope of which is defined only by the claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.

[0082] Unless otherwise indicated, all numbers used in the specification and claims to indicate lengths, widths, depths, or other dimensions, etc. should be understood in all instances to refer to both the exact value as shown and the value modified by the term "about". As used herein, the term "about" means a variation of ±20% from the nominal value.

[0083] Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and the appended claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Any particular value may vary by 20%.

[0084] The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. Accordingly, the foregoing embodiments are to be considered in all respects illustrative rather than limiting of the invention described herein. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.

[0085] Those skilled in the art should understand that various modifications and changes can be made without departing from the scope of the described technology. Such modifications and changes are intended to fall within the scope of the described embodiments. Those skilled in the art will also understand that the features included in one embodiment can be interchanged with those of other embodiments; and one or more features from the described embodiments can be included in any combination with other described embodiments. For example, any of the various components described herein and / or depicted in the drawings can be combined with, interchanged with, or excluded from other embodiments.

Claims

1. A magnetic blood filter assembly, comprising: a first magnet; a filter housing defining an input port and an output port, the input port being configured to receive blood; the filter housing having a first surface, a second surface, and one or more wall surfaces, the first surface, the second surface, and the one or more wall surfaces defining a volume, the first magnet being positioned on the first surface of the filter housing; and a stack of a plurality of meshes, wherein the plurality of meshes includes a first mesh, the first mesh including a plurality of filaments, the stack of the plurality of meshes being disposed within the filter housing, the first mesh being in fluid communication with the input port, and the plurality of filaments including magnetizable material; wherein a magnetic field generated by the first magnet is substantially perpendicular to the stack of the plurality of meshes and strong enough to induce a magnetic field in the magnetizable material, thereby generating a high magnetic field gradient in one or more regions near the surface of each of the plurality of filaments, wherein a blood-borne magnetic target is captured in the one or more regions having the high magnetic field gradient, and the magnetic field is substantially parallel to the fluid flow through the filter housing; wherein the first magnet is arranged to generate a non-uniform magnetic field near one or more of the plurality of filaments.

2. The blood filter assembly according to claim 1, wherein the one or more regions define a stationary capture region configured to capture magnetically labeled biomolecules.

3. The blood filter assembly according to claim 1, wherein the stack of the plurality of meshes is arranged to define a laminar flow path through at least one of the volumes.

4. The blood filter assembly according to claim 1, wherein the plurality of meshes are arranged in a random and misaligned configuration.

5. The blood filter assembly according to claim 1, wherein the sizes of the input port and the output port are selected to support a flow rate range between the input port and the output port from 40 to 400 ml / min.

6. The blood filter assembly according to claim 1, wherein the first mesh defines a weave of the plurality of filaments, wherein the weave is configured such that an area of substantially maximized magnetic drag force overlaps an area of substantially minimized viscoelastic drag force.

7. The blood filter assembly according to claim 1, wherein the plurality of mesh pores are arranged such that blood passing therethrough separates into one or more laminar flows, and the one or more laminar flows separate and recombine as the one or more laminar flows move through one or more of the plurality of meshes.

8. The blood filter assembly according to claim 1, wherein the first mesh is selected such that the Reynolds number of the blood passing through the stack of the plurality of meshes is less than 2300 or 2300.

9. The blood filter assembly according to claim 1, wherein the arrangement of the stack of the plurality of meshes is selected to avoid dead spots with respect to blood flowing through the stack of the plurality of meshes.

10. The blood filter assembly according to claim 1, wherein The stacking of the plurality of meshes defines one or more stationary capture zones to keep one or more targets in the blood flowing near one or more of the plurality of filaments.

11. The blood filter assembly according to claim 1, wherein, the first magnet is one of a plurality of magnets or a pair of magnets.

12. The blood filter assembly according to claim 1, wherein, the first mesh is woven from the plurality of filaments, and the first mesh has a pore spacing ranging from 10 to 1000 microns.

13. The blood filter assembly according to claim 1, further comprising a second magnet, wherein the first magnet and the second magnet are arranged on opposite sides of the filter housing.

14. The blood filter assembly according to claim 1, wherein, the filter housing is configured to increase the flow rate by reducing the drag force.

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