Systems and methods for controlled dosing of non-suspended particles

Abstract

Systems and methods for controlled administration of non-suspended particles are disclosed herein. The system can include an agitation mechanism, at least one reservoir, an infusion mechanism, and a delivery conduit. The system can be configured to infuse non-uniformly or uniformly dispersed non-suspended particles to a patient.

Description

Technical Field

[0001] This invention relates to systems and methods for controlled administration of non-suspended particles. The system may include a stirring mechanism, an infusion mechanism, at least one reservoir, and a delivery catheter. The system can be configured to infuse a patient with non-uniformly or uniformly dispersed non-suspended particles. Background Technology

[0002] In recent years, nanoparticles have played a crucial role in modern medicine, with applications ranging from contrast agents in medical imaging to carriers for delivering genes into individual cells. Nanoparticles possess many properties that distinguish them from bulk materials solely by their size, such as chemical reactivity, energy absorption, and biofluidity. In the medical field, an important subclass of nanoparticles is magnetic nanoparticles (MNPs). Magnetic nanoparticles (MNPs), including magnetic iron oxide nanoparticles, have enormous potential in many biomedical applications, such as biomolecule separation, MRI imaging, thermotherapy, iron supplementation, and tumor embolization. MNPs can be used as carriers for drugs, nucleic acids, peptides, and other bioactive compounds. Intravenous injection is a common method of nanoparticle administration.

[0003] Known nanoparticle infusion systems in the art require specially prepared suspensions to maintain uniformly dispersed particles for infusion into patients or devices used to analyze the particles. Some nanoparticle applications require magnetic nanoparticles; however, MNP suspensions require thick buffer layers to maintain uniform dispersion of magnetic nanoparticles. In many cases, thicker buffer layers reduce the effectiveness of the nanoparticle core and the overall magnetization of the nanoparticles, thus necessitating the use of stronger magnets to control the nanoparticles on demand.

[0004] Therefore, a system is needed for uniformly dispersing and controlling the administration of non-suspended nanoparticles, particularly for magnetic nanoparticles with thin buffer layers or coatings. Summary of the Invention

[0005] This document provides a system for controlled delivery of non-suspended particles. The system may include: at least one reservoir operable to contain a plurality of non-suspended particles and / or a carrier fluid; a stirring mechanism operable to stir the non-suspended particles in the at least one reservoir; and a delivery conduit in fluid communication with the at least one reservoir. In one aspect, the stirring mechanism provides mechanical agitation of the non-suspended particles to uniformly disperse the plurality of non-suspended particles. In another aspect, the at least one reservoir is the barrel of a syringe. In some aspects, the syringe includes a plunger operable to expel the plurality of non-suspended particles and / or the carrier fluid from the barrel into the delivery conduit. In one aspect, the stirring mechanism is a rocker plate coupled to the barrel. In another aspect, the system includes one or more stirring elements within the barrel of the syringe. In one aspect, the rocker plate is operable to stir the one or more stirring elements, thereby mechanically and uniformly dispersing the non-suspended particles in the barrel.

[0006] In another aspect, the stirring mechanism may be a circulation mechanism. The circulation mechanism may include a first syringe having a barrel and a plunger, and a second syringe having a barrel and a plunger. The first syringe may be in fluid communication with the second syringe. The circulation mechanism may also include a third syringe having a barrel and a plunger. The barrel of the third syringe may be the at least one reservoir containing the carrier fluid. In one aspect, the first syringe and the second syringe contain the plurality of unsuspended particles. In some aspects, the system may include a manifold in fluid communication with the first syringe, the second syringe, the third syringe, and the delivery conduit. The plungers of the first syringe and the second syringe are operable to compress and / or depressurize to circulate the unsuspended particles through the manifold between the first syringe and the second syringe, thereby mechanically and uniformly dispersing the unsuspended particles. The plunger of the third syringe is operable to be compressed and discharge the carrier fluid into the manifold. In one aspect, the carrier fluid in the manifold may entrain some of the plurality of unsuspended particles, thereby providing the entrained unsuspended particles to the delivery conduit.

[0007] In another aspect, the stirring mechanism may be a magnetic stirrer assembly. The magnetic stirrer assembly may include a magnetic stirrer fan. The at least one reservoir may be a syringe having a barrel and a plunger. In one aspect, the magnetic stirrer assembly may be coupled to the interior of the syringe barrel. The system may also include an external magnet subassembly configured to rotate to cause a change in the magnetic field operable to rotate the magnetic stirrer fan. Rotation of the magnetic stirrer fan mechanically and uniformly disperses the unsuspended particles in the syringe barrel. The plunger is operable to discharge the uniformly dispersed unsuspended particles and the carrier fluid into the delivery conduit.

[0008] In another aspect, the stirring mechanism may be a peristaltic pump. The carrier fluid may be contained in the at least one reservoir, and the unsuspended particles may be contained in the peristaltic reservoir. The peristaltic pump may provide pressure to the unsuspended particles in the peristaltic reservoir, thereby uniformly dispersing the unsuspended particles. In one aspect, the at least one reservoir is a syringe having a barrel and a plunger in fluid communication with the peristaltic reservoir. The plunger is operable to provide the carrier fluid to the peristaltic reservoir and entrain the uniformly dispersed unsuspended particles. In one aspect, the peristaltic reservoir is in fluid communication with the delivery conduit. The entrained unsuspended particles and the carrier fluid may be delivered to the delivery conduit by the pressure provided by the peristaltic pump.

[0009] In one aspect, the non-suspended particles may be magnetic nanoparticles, and the carrier fluid may be physiological saline.

[0010] This document also provides a system for controlled delivery of non-suspended particles. The system may include: at least one reservoir containing a plurality of non-suspended particles, a carrier fluid, and one or more agitators. The system may further include a stirring mechanism operable to mechanically agitate the one or more agitators, thereby uniformly dispersing the plurality of non-suspended particles. The system may also include a delivery conduit in fluid communication with the at least one reservoir. The delivery conduit is operable to deliver the uniformly dispersed non-suspended particles and the carrier fluid to a patient. In one aspect, the stirring mechanism may be a rocker plate coupled to the at least one reservoir.

[0011] This document also provides a system for controlled delivery of non-suspended particles. The system may include a first reservoir and a second reservoir containing a plurality of non-suspended particles. The first reservoir may be in fluid communication with the second reservoir. The first and second reservoirs may also be in fluid communication with a manifold. The system may include a third reservoir containing a carrier fluid. The third reservoir may be in fluid communication with the manifold. The system may also include a delivery catheter in fluid communication with the manifold. The non-suspended particles may be circulated between the first and second reservoirs via the manifold by means of a pressure source, thereby uniformly dispersing the plurality of non-suspended particles. The carrier fluid may be discharged from the third reservoir by means of a second pressure source, entraining some of the non-suspended particles that have passed through the manifold. The non-suspended particles entrained in the carrier fluid may be delivered to a patient via the delivery catheter.

[0012] This document also provides a system for controlled delivery of non-suspended particles. The system may include at least one reservoir containing a plurality of non-suspended particles and a carrier fluid. The system may include a magnetic stirrer fan assembly having a magnetic stirrer fan and being coupled within the at least one reservoir. An external magnet assembly may be located externally near the at least one reservoir. The system may include a delivery conduit in fluid communication with the at least one reservoir. Rotation of the external magnet assembly may cause rotation of the magnetic stirrer fan. Rotation of the magnetic stirrer fan may cause fluid mixing of the plurality of non-suspended particles in the at least one reservoir. The fluid-mixed non-suspended particles may be uniformly dispersed in the carrier fluid. The uniformly dispersed non-suspended particles and the carrier fluid may be discharged from the at least one reservoir into the delivery conduit by means of a pressure source.

[0013] This document also provides a system for controlled drug delivery of non-suspended particles. The system may include a first reservoir containing a carrier fluid. The first reservoir may be in fluid communication with a peristaltic reservoir containing a plurality of non-suspended particles. The system may include a peristaltic pump in fluid communication with the peristaltic reservoir. The peristaltic pump is operable to provide pressure to the peristaltic reservoir, thereby uniformly dispersing the plurality of non-suspended particles. The carrier fluid may be provided to the peristaltic reservoir by means of a pressure source. The carrier fluid may entrain the non-suspended particles in the peristaltic reservoir. The carrier fluid and the entrained non-suspended particles may be provided to a delivery conduit by means of the pressure provided by the peristaltic pump.

[0014] This article also provides a method for controlled administration of non-suspended particles. The method may include: providing a plurality of non-suspended particles to at least one reservoir; agitating the plurality of non-suspended particles in the at least one reservoir via a stirring mechanism; entraining the plurality of non-suspended particles in a carrier fluid; and delivering the plurality of non-suspended particles entrained in the carrier fluid to a patient or infusion device via a delivery conduit.

[0015] Other aspects and iterative forms of the invention are described more thoroughly below. Attached Figure Description

[0016] The description will be more fully understood with reference to the following accompanying drawings and graphs, which are presented as various embodiments of the invention and should not be construed as a complete statement of the scope of the invention. It should be noted that, for clarity, some elements in the various drawings may not be drawn to scale. It should be understood that these drawings depict only exemplary embodiments of the invention and should therefore not be considered as limiting its scope. The principles herein are described and explained in a more specific and detailed manner using the drawings, wherein:

[0017] Figure 1A This is an example of a system for controlled delivery of non-suspended particles.

[0018] Figure 1B This is an example of a system for controlled delivery of non-suspended particles.

[0019] Figure 1C This is an example of a system for controlled delivery of non-suspended particles.

[0020] Figure 1D This is an example of a system for controlled delivery of non-suspended particles.

[0021] Figure 2A This is an example of a system for controlled delivery of non-suspended particles.

[0022] Figure 2B This is an example of a system for controlled delivery of non-suspended particles.

[0023] Figure 2C This is an example of a system for controlled delivery of non-suspended particles.

[0024] Figure 2D This is an example of a system for controlled delivery of non-suspended particles.

[0025] Figure 3A This is an example of a system for controlled delivery of non-suspended particles.

[0026] Figure 3BThis is an example of a system for controlled delivery of non-suspended particles.

[0027] Figure 3C This is a sample magnetic stirrer component.

[0028] Figure 3D This is an exploded view of a magnetic stirrer component in an example.

[0029] Figure 4 This is an example of a system for controlled delivery of non-suspended particles.

[0030] Figure 5 This is a graph illustrating the transport of non-suspended particles in an example.

[0031] Figure 6 This is a graph illustrating the transport of non-suspended particles in an example.

[0032] Figure 7 This is a flowchart illustrating an example of a method for controlling the administration of non-suspended particles.

[0033] Reference numerals in the accompanying drawings denote corresponding elements in the views. The headings used in the drawings do not limit the scope of the claims. Detailed Implementation

[0034] Various embodiments of the present invention are discussed in detail below. While specific implementations are discussed, it should be understood that this is for illustrative purposes only. Those skilled in the art will recognize that other components and configurations can be used without departing from the spirit and scope of the invention. Therefore, the following description and drawings are illustrative and should not be construed as limiting. Numerous specific details are described to provide a thorough understanding of the invention. However, in some cases, well-known or conventional details have not been described to avoid obscuring the description. References to one embodiment or an embodiment in this invention may refer to the same embodiment or any embodiment; and such references imply at least one embodiment.

[0035] References to "one embodiment," "an embodiment," or "an aspect" mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the invention. The phrases "in one embodiment" or "in an aspect" appearing in various places in the specification do not necessarily refer to the same embodiment, nor are they necessarily separate or alternative embodiments that are mutually exclusive with other embodiments. Furthermore, various features that may be exhibited by some embodiments but not by others are described.

[0036] The terms used in this specification generally have their ordinary meaning in the art, in the context of this invention, and in the specific context in which each term is used. Alternative languages ​​and synonyms may be used for any one or more terms discussed herein, and whether or not a term is described or discussed in detail herein should not be considered to have a particular meaning. In some cases, synonyms for certain terms are provided. The recitation of one or more synonyms does not preclude the use of other synonyms. Examples used anywhere in this specification, including examples of any terms discussed herein, are merely illustrative and are not intended to further limit the scope and meaning of the invention or any of the example terms. Similarly, the invention is not limited to the various embodiments given in this specification.

[0037] As used herein, “about” refers to a numerical value, including integers, fractions, percentages, etc., whether explicitly stated or not. The term “about” generally refers to a series of numerical values, such as ±0.5-1%, ±1-5%, or ±5-10% of the stated value, which should be considered equal to the stated value, for example, having the same function or result.

[0038] In this invention, the terms "nanoparticle," "particle," "microbead," and "microparticle" are used interchangeably. A nanoparticle is a material having an overall size in the nanometer range (e.g., less than 100 nm). Some definitions extend this to 500 nm (or even 1000 nm), but here the definition of a nanoparticle will be those particles with an overall size less than 100 nm. For the purposes of this application, fine particles will have a size of 100 nm to 2500 nm, and coarse particles will have a size of 2500 nm to 10000 nm. Particles may also include embolic microbeads with a size of 50000 nm to 250000 nm. Embolizing microbeads include magnetic embolic microbeads. Nanoparticles, fine particles, coarse particles, and embolic microbeads are collectively referred to as particles in this application (although other known definitions of these terms use microparticle size to distinguish between particles and nanoparticles).

[0039] Additional features and advantages of the invention will be set forth in the description which follows (and some features and advantages will become apparent from the description), or may be learned by practicing the principles disclosed herein. The features and advantages of the invention can be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of the invention will become more apparent from the following description and the appended claims, or may be learned by practicing the principles described herein.

[0040] Intravenous injection is a common method for nanoparticle drug delivery. However, the systems and methods described herein can be used for intra-arterial and intrathecal drug delivery, as well as intravenous injection. In these applications, nanoparticles must typically be uniformly distributed in a carrier medium (such as saline) for controlled delivery of the intended nanoparticle therapy. This is usually achieved by formulating the nanoparticles as a suspended solid (or material) within the carrier medium. A suspended solid refers to small solid particles that remain suspended in a medium (such as saline) as a colloid or technically due to the movement of the medium. This suspension requirement (often referred to as particle stability) limits the design of nanoparticles. For magnetic nanoparticles (MNPs), this requirement and the addition of coatings can alter particle controllability, i.e., increase the magnetic field and / or force required to control the particles. For example, for suspended particles, to promote uniform dispersion, the coating must increase the distance between the cores to reduce the attraction of particles above the superparamagnetic size range, thereby reducing the magnetic properties of the particles. This minimum distance varies with the core size. Another function of the coating is to reduce the overall density of the particle, both for magnetic and non-magnetic particles with a high density relative to the carrier fluid.

[0041] This article provides a system for controlled delivery of non-suspended particles, eliminating the need to suspend the particles for intravenous injection or other applications. The delivery of non-suspended particles can be used in the medical field, or other technical fields such as engineering and agriculture. The system agitates the non-suspended particles to ensure uniform distribution for infusion.

[0042] The system described herein includes at least one reservoir for containing non-suspended particles, a delivery conduit, a stirring mechanism, and an infusion mechanism (e.g., a syringe). In some examples, at least one reservoir may be a component of the infusion mechanism (e.g., the barrel of a syringe). In some examples, the system may include a carrier fluid. In one example, the carrier fluid and non-suspended particles may be placed in the same reservoir. In other examples, the non-suspended particles and the carrier fluid may be placed in different reservoirs, and the carrier fluid may later be combined (mixed) with the non-suspended particles.

[0043] A stirring mechanism uniformly disperses non-suspended particles, which are then entrained in a carrier fluid. The entrained, uniformly dispersed non-suspended particles (e.g., a homogeneous mixture) can then be delivered to the patient or infusion device via a delivery catheter. In some examples, the non-suspended particles may be dispersed non-uniformly with a desired dispersion (i.e., distribution) profile. The system is operable to achieve the desired particle infusion over time, regardless of whether the infusion uses fully uniformly dispersed or non-uniformly dispersed non-suspended particles.

[0044] In some examples, the pressure source is operable to expel unsuspended particles and / or carrier fluid from the reservoir described herein. While specific examples of syringe systems are shown and described herein, the pressure source can be a pressure source different from the plunger of the syringe. In some examples, the pressure source can be any type of pump, mechanically or fluidly connected to the system, and operable to provide pressure to move unsuspended particles and / or carrier fluid through the various components of the system.

[0045] In one aspect, the non-suspended particles can be nanoparticles, microparticles, chemicals, metals, or any material with a density different from that of the carrier fluid. In one example, the non-suspended particles can be magnetic nanoparticles (MNPs). In other examples, the non-suspended particles can be liposomes, proteins, microvesicles, and / or polymer constructs. In some examples, the polymer construct can be embolic microbeads, such as polymers linked to gelatin or other absorbable polymers (e.g., polyacrylic acid, polyvinyl alcohol, etc.). It should be understood that the non-suspended particles can be any particles that can be used for infusion into a patient and / or for infusion into another application requiring a uniform or controlled non-uniform dispersion of particles.

[0046] MNPs for injectable applications typically range in size from 1 nm to 100 nm. Furthermore, nanostructures for injectable applications are often coated with polymers such as polyethylene glycol, dextran, or silanes to provide stability and prevent aggregation. Dextran-coated iron oxide (Fe3O4) nanoparticles with sizes ranging from 80 nm to 150 nm and dextran-coated MNPs with sizes ranging from 20 nm to 40 nm are examples of MNPs used for mononuclear phagocyte system imaging, lymph node and perfusion imaging, and cell labeling. Other MNPs with sizes ranging from about 50 nm to about 250 nm can be used with the systems described herein. MNPs can be administered using the systems described herein. Other particle sizes can be used in the systems and methods described herein. For example, particles with sizes from about 20 µm to about liposomes can be used. Additionally, embolic microbeads with sizes from about 50 µm to about 250 µm can be administered using the systems described herein. Other particles ranging in size from about 1 nm to about 250 µm can be administered using the systems described herein.

[0047] Figures 1A-1DA mechanical stirring system 100 for controlled administration of non-suspended particles is shown. The mechanical stirring system 100 may include an infusion mechanism. In some examples, the infusion mechanism may be a syringe 108. The syringe 108 may have a plunger 103 and a barrel 102 (e.g., a reservoir). The barrel 102 may be a cylindrical body. The plunger may have a plunger end 110 disposed within the barrel 102 (e.g., the cylindrical body) of the syringe 108. The plunger 103 may move linearly within the barrel 102. In some examples, the plunger may operate as a pressure mechanism for discharging the contents of the syringe into a tube or catheter. The syringe may be in fluid communication with a delivery catheter 114. The delivery catheter 114 is operable to provide non-suspended particles to a patient or infusion device. In other examples, the infusion mechanism may include any reservoir capable of containing a carrier fluid 104 and non-suspended particles 105, and any mechanism for moving the carrier fluid 104 and non-suspended particles into the delivery catheter 114.

[0048] In one example, syringe 108 can be oriented horizontally, such as Figures 1A-1D As shown. In another example, syringe 108 can be oriented vertically. In yet another example, syringe 108 can be oriented in any other configuration.

[0049] In one aspect, the carrier fluid 104 may be physiological saline. In other examples, other carrier fluids operable to be infused into a patient may be used. In other non-medical applications, other known carrier fluids may be used.

[0050] In some aspects, the syringe barrel 102 may be filled with a carrier fluid 104, non-suspended particles 105, and one or more agitators 106. In some examples, the agitator 106 may be biosafe, sterile, and / or non-reactive. The agitator 106 may be configured to prevent leaching or degassing. In some examples, the agitator 106 may be made of plastic, glass, metal, or other materials. In various examples, the agitator 106 may be specifically shaped such that the agitator 106 uniformly disperses the non-suspended particles 105 during agitation. For example, the agitator 106 may be a sphere, oblate spheroid, elongated sphere, cylinder, cone, cube, cuboid, pyramid, prism, or other geometry. The agitator 106 may have dimensions ranging from about 1 mm to about 10 mm. In one example, the agitator 106 may be a 4 mm sphere.

[0051] In one aspect, the mechanical mixing system 100 may include about 1 to about 5 mixing bodies 106, about 5 to about 10 mixing bodies 106, about 10 to about 15 mixing bodies 106, about 15 to about 20 mixing bodies 106, about 20 to about 25 mixing bodies 106, about 25 to about 30 mixing bodies 106, about 30 to about 35 mixing bodies 106, about 35 to about 40 mixing bodies 106, about 40 to about 45 mixing bodies 106, about 45 to about 5 mixing bodies 106. 0 mixing volumes 106, about 50 to about 55 mixing volumes 106, about 55 to about 60 mixing volumes 106, about 60 to about 65 mixing volumes 106, about 65 to about 70 mixing volumes 106, about 70 to about 75 mixing volumes 106, about 75 to about 80 mixing volumes 106, about 80 to about 85 mixing volumes 106, about 85 to about 90 mixing volumes 106, about 90 to about 95 mixing volumes, about 95 to about 100 mixing volumes, or more. In another example, the mechanical mixing system 100 may include about 1 to about 100 mixing bodies 106, about 100 to about 200 mixing bodies 106, about 200 to about 300 mixing bodies 106, about 300 to about 400 mixing bodies 106, about 400 to about 500 mixing bodies 106, about 500 to about 600 mixing bodies 106, about 600 to about 700 mixing bodies 106, about 700 to about 800 mixing bodies 106, about 800 to about 900 mixing bodies 106, about 900 to about 1000 mixing bodies 106, or more.

[0052] The agitator 106 may also have a hardness sufficient to prevent the formation of wear products. For example, the agitator 106 may have a hardness greater than that of the core of the particles. For example, if the core of the particles is a magnetite core, the agitator 106 may have a hardness of at least about 5.5 Mohs. In another example, if the core of the particles is silica, the agitator 106 may have a hardness of at least 7 Mohs. In some examples, the agitator may have a hardness of about 5.5 Mohs to about 6 Mohs, about 6 Mohs to about 6.5 Mohs, about 6.5 Mohs to about 7 Mohs, about 7 Mohs to about 7.5 Mohs, about 7.5 Mohs to about 8 Mohs, about 8 Mohs to about 8.5 Mohs, about 8.5 Mohs to about 9 Mohs, about 9 Mohs to about 9.5 Mohs, or about 9.5 Mohs to about 10 Mohs. It should be understood that the hardness of the agitator 106 can be selected for different applications based on the hardness of the particle core.

[0053] The stirrer 106 may have a different density than the carrier liquid 104. In some examples, the stirrer 106 may have a higher density than the carrier liquid 104. In another example, the stirrer 106 may have a lower density than the carrier liquid 104.

[0054] In one aspect, the mechanical stirring system 100 may include a stirring mechanism configured to stir one or more stirring elements 106 within the barrel 102 of the syringe to disperse unsuspended particles 105 in a carrier liquid 104. For example, the stirring mechanism may be a rocker 116 (e.g., a reciprocating plate). The rocker 116 may be coupled to the barrel 102 of the syringe 108. The rocker 116 may include a hub 117 and a base 118. The base 118 may be connected to a power source to power the rocker 116. In some examples, the rocker 116 may be actuated by a motor. The hub 117 may allow the rocker 116 to move. The rocker 116 may be configured to move such that the stirring elements 106 are stirred. The rocker 116 may cause the barrel 102 to reciprocate. The rocker movement 124 causes the stirring elements 106 to move within the barrel 102 of the syringe, thereby mechanically and uniformly dispersing the unsuspended particles 105 in the carrier liquid 104. The rocker motion 124 can be forward and backward, left and right, up and down, circular, elliptical, non-linear repetitive motion (e.g., tilting, swaying, metronome motion, pendulum motion, and / or other non-linear repetitive motion), or a combination thereof.

[0055] In some aspects, the rocker 116 may have one or more frequencies and one or more amplitudes. In some examples, the frequency of the rocker 116 may be about 0.5 Hz to about 5 Hz, about 5 Hz to about 10 Hz, about 10 Hz to about 15 Hz, about 15 Hz to about 20 Hz, about 20 Hz to about 25 Hz, about 25 Hz to about 30 Hz, about 30 Hz to about 35 Hz, about 35 Hz to about 40 Hz, about 40 Hz to about 45 Hz, about 45 Hz to about 50 Hz, about 50 Hz to about 55 Hz, about 55 Hz to about 60 Hz, or higher. The amplitude of the rocker 116 may depend on the type of motion. For example, the amplitude can be approximately 1 cm to approximately 2 cm, approximately 2 cm to approximately 3 cm, approximately 3 cm to approximately 4 cm, approximately 4 cm to approximately 5 cm, approximately 5 cm to approximately 6 cm, approximately 6 cm to approximately 7 cm, approximately 7 cm to approximately 8 cm, approximately 8 cm to approximately 9 cm, approximately 9 cm to approximately 10 cm, approximately 10 cm to approximately 15 cm, approximately 15 cm to approximately 20 cm, approximately 20 cm to approximately 25 cm, approximately 25 cm to approximately 30 cm, or greater. In one example, when the rocker motion 124 is circular, the amplitude can be approximately 3 cm. In another example, when the rocker motion 124 is circular, the amplitude can be approximately 1 cm to approximately 5 cm. In yet another example, the rocker motion 124 can be a metronome-like or pendulum-like motion, and the amplitude can be approximately 20 cm. In yet another example, the rocker motion 124 can be a metronome-like or pendulum-like motion, and the amplitude can be approximately 10 cm to approximately 30 cm.

[0056] In some respects, the frequency of the shaker can be selected to control the uniform dispersion of the non-suspended particles 105, the heating of the non-suspended particles 105 and the carrier liquid 104, and / or the vibration of the system. For example, the frequency of the shaker 116 can directly affect the heating of the carrier liquid 104 and the non-suspended particles 105 over a given duration. The higher the frequency of the shaker 116, the greater the increase in heat within the syringe barrel 102 due to the movement of the agitator 126 over a given duration.

[0057] In one aspect, syringe 108 may have a syringe interface 112 at its proximal end. Syringe interface 112 may be in fluid communication with a delivery conduit 114 (e.g., an infusion line). In some examples, delivery conduit 114 may have an inner diameter of about 0.1 mm to about 1 mm. In another example, the inner diameter of the delivery conduit may be about 0.1 mm to about 1 mm, about 1 mm to about 2 mm, about 2 mm to about 3 mm, about 3 mm to about 4 mm, or about 4 mm to about 5 mm. Syringe interface 112 may have a diameter smaller than the minimum size of the agitator 106, thereby preventing the agitator 106 from entering the delivery conduit 114. The agitator 106 may be retained within the barrel 102 throughout the infusion process.

[0058] In some respects, the movement of the agitator 106 can heat the carrier fluid 104 and / or non-suspended particles 105 within the syringe barrel 102. The heat generated can be below the patient's body temperature. In some examples, the non-suspended particles 105 and carrier fluid 104 are delivered to the patient at a temperature below the patient's body temperature.

[0059] In some examples, the mechanical stirring system 100 may also include a cooling mechanism. The cooling mechanism is operable to cool the non-suspended particles 105 and the carrier fluid 104 within the barrel 102 of the syringe. In some examples, the cooling mechanism may be a fan operable to supply cooling air to the outside of the barrel 102 of the syringe. In some examples, the cooling air may be at or below room temperature. In other examples, the cooling mechanism may be a chemical cooling mechanism. A cooling body may be placed within the barrel 102 of the syringe 108 such that when the rocker 116 begins to move the stirring body 106, the cooling body is activated, thereby providing a cooling effect on the carrier fluid 104 and the non-suspended particles 105. In a further example, the barrel 102 of the syringe may be enclosed in a cooling jacket to allow energy to be transferred from the syringe, thereby cooling the carrier fluid 104 and the non-suspended particles 105 within the barrel 102 of the syringe. The temperature of the carrier fluid 104 and the non-suspended particles 105 is approximately 4 degrees Celsius to approximately 37 degrees Celsius. In some examples, the non-suspended particles 105 and the carrier fluid 104 are delivered to the patient at a temperature below the patient's body temperature. In some examples, the non-suspended particles 105 and the carrier fluid 104 can be administered at a temperature around room temperature. It should be understood that a cooling mechanism can be used with any of the systems described herein.

[0060] Figures 1A-1D The movement of rocker 116 is shown. For example... Figure 1A As shown, the rocker 116 can start from the first position 101. The rocker 116 and the rocker hub 117 can initiate rocker movement 124 to the second position 121, for example as... Figure 1B As shown. In this example, the rocker 116 moves in a left-right or back-and-forth motion. When the rocker 116 begins its rocker movement 124 in a rearward direction (e.g., toward the plunger 103 of the syringe), the agitator 106 can move forward (e.g., toward the syringe port 112), as shown by the agitator movement 126. In the third position 131, as... Figure 1C As shown, the rocker plate moves 124 in the forward direction, thereby causing the agitator to move 126 in the rearward direction (e.g., toward the plunger 103 of the syringe). In the fourth position 141, as... Figure 1D As shown, the rocker motion 124 can be in a rearward direction (e.g., toward the plunger 103 of the syringe), thereby causing the agitator motion 126 to be in a forward direction (e.g., toward the syringe port 112). By generating the rocker motion 124 and the agitator motion 126, the non-suspended particles 105 become mechanically and uniformly dispersed in the carrier liquid 104.

[0061] In one aspect, the plunger 103 of the syringe is operable to deliver the unsuspended particles 105 to a patient by applying a force 122 (e.g., compressing the plunger 103) to the plunger 103, thereby pushing the unsuspended particles 105 and the carrier fluid 104 into the delivery catheter 114. In some examples, the rocker motion 124 and the agitator motion 126 may occur during a preheating period before delivery begins, by compressing the plunger 103 of the syringe. For example, the preheating period may be about 1 second to about 5 seconds, about 5 seconds to about 10 seconds, about 10 seconds to about 15 seconds, about 15 seconds to about 20 seconds, about 20 seconds to about 25 seconds, about 25 seconds to about 30 seconds, about 30 seconds to about 35 seconds, about 35 seconds to about 40 seconds, about 40 seconds to about 45 seconds, about 45 seconds to about 50 seconds, about 50 seconds to about 55 seconds, about 55 seconds to about 1 minute, about 1 minute to about 2 minutes, about 2 minutes to about 3 minutes, about 3 minutes to about 4 minutes, or about 4 minutes to about 5 minutes. In other examples, no preheating period is required, and the plunger 103 and rocker plate 116 of the syringe can be activated simultaneously.

[0062] In some aspects, the inner diameter of the delivery conduit 114, the viscosity of the carrier fluid 104, the density of the unsustainable particles 105, and the hydrodynamic diameter of the unsustainable particles 105 can determine the critical flow rate for maintaining the unsustainable particles 105 entrained in the carrier fluid 104. Once the critical flow rate for maintaining the unsustainable particles entrained in the carrier fluid 104 is determined, this critical flow rate can be multiplied by the inner diameter of the delivery conduit 114 to determine the required flow rate of the carrier fluid 104 for entraining the unsustainable particles. Using this determined flow rate, the pressure required to achieve the required flow rate of the carrier fluid 104 for entraining the unsustainable particles 105 can be determined, thereby determining the force 122 supplied to the plunger 103 of the syringe. In some examples, the carrier fluid flow rate is sufficient to entrain the unsustainable particles 105 in the carrier fluid 104, thereby maintaining a uniform dispersion of the unsustainable particles 105. By entraining the unsustainable particles 105, it is ensured that the unsustainable particles 105 do not settle from the carrier fluid and accumulate on the sidewalls of the conduit. It should be understood that the determination of the critical flow rate and flow rate of the entrained carrier fluid 104 is applicable to all systems and methods disclosed herein.

[0063] In some examples, the critical flow rate for entraining the non-suspended particles 105 in physiological saline can be 10 cm / s. In this example, when the critical flow rate for entraining the non-suspended particles 105 in physiological saline is 10 cm / s, the required flow rate of the carrier fluid 104 for a delivery catheter 114 with an inner diameter of 0.5 mm is 1.2 mL / min. In another example, the critical flow rate for entraining the non-suspended particles 105 in water can be 3 cm / s. In this example, for a delivery catheter with an inner diameter of 1.7 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 4 mL / min. In another example, the flow rate of the carrier fluid 104 can be 6 cm / s. In this example, for a delivery catheter with an inner diameter of 0.5 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 0.66 mL / min. It should be understood that other flow rates can be selected based on the critical flow rate required to carry the non-suspended particles 105 and the inner diameter of the delivery conduit 114.

[0064] In other examples, the non-suspended particles 105 can be delivered at a desired non-uniform rate. The non-uniform rate can be achieved by continuously adding more carrier fluid 104 or dynamically changing the volumetric flow rate to dynamically adjust the concentration of non-suspended particles 105 in at least one reservoir (e.g., the barrel 102 of a syringe).

[0065] In another aspect, the non-suspended particles 105 can be mechanically and uniformly dispersed in the second reservoir. In this example, the non-suspended particles 105 and the agitator 106 are not placed in the barrel 102 of the syringe 108, but are held in the second reservoir. A rocker 116, a rocker hub 117, and a rocker seat 118 can be coupled to the second reservoir. The rocker 116 can move the agitator 106, thereby uniformly dispersing the non-suspended particles 105 in the second reservoir. The syringe port 112 can be in fluid communication with the second reservoir via a tube (e.g., a conduit). By compressing the plunger 103, the carrier fluid 104 can be discharged from the syringe port 112 and enter the tube connecting the syringe 108 to the second reservoir. The non-suspended particles 105 are then infused into the second reservoir together with the carrier fluid 104. The carrier fluid 104 enters the second reservoir at a sufficient flow rate so that the mechanically mixed non-suspended particles 105 are infused with the desired uniformity. In other examples, non-suspended particles 105 can be entrained in the carrier liquid 104 at a desired non-uniform rate.

[0066] Figures 2A-2DAnother example of a mechanical stirring system 200 is shown. The mechanical stirring system 200 may include a stirring mechanism (e.g., a circulation mechanism) comprising a first injector 256 (e.g., a stirring injector), a second injector 258 (e.g., a stirring injector), and a third injector 254 (e.g., an infusion injector). The third injector may have a plunger 232 and a barrel 230 (e.g., a third reservoir). A carrier fluid 233 (i.e., an infusion fluid for entraining non-suspended particles) may be held within the barrel 230 of the third injector 254. The interface of the third injector 254 may be in fluid communication with a first manifold 236. The first manifold is operable to supply the carrier fluid 233 to a manifold 240. The first injector 256, the second injector 258, and the third injector 254 may be in fluid communication with this manifold.

[0067] In some aspects, the first syringe 256 may have a plunger 212 and a barrel 210 (e.g., a first reservoir). Unsuspended particles 213 may be retained within the barrel 210 of the first syringe 256. The first syringe 256 may have an interface in fluid communication with a second manifold 216. The second manifold 216 is operable to supply unsuspended particles 213 to a manifold 240. In some examples, the second manifold 216 may also be operable to supply unsuspended particles 213 from the manifold 240 to the first syringe 256.

[0068] In one aspect, the second syringe 258 may have a plunger 222 and a barrel 220 (e.g., a second reservoir). Unsuspended particles 213 may be retained within the barrel 220 of the second syringe 258. The second syringe 258 may have an interface in fluid communication with a third manifold conduit 226. The third manifold conduit 226 is operable to supply unsuspended particles 213 to the manifold. In some examples, the third manifold conduit 226 may also be operable to supply unsuspended particles 213 from the manifold 240 to the second syringe 258.

[0069] In some aspects, manifold 240 may have four inlets / outlets. A first inlet of manifold 240 may be in fluid communication with a first manifold conduit 236. The first inlet may allow flow in only one direction (e.g., from the third injector 254 to manifold 240). The first inlet is operable to receive a carrier fluid 233 from the third injector 254. A second inlet / outlet of manifold 240 may be in fluid communication with a second manifold conduit 216. The second inlet / outlet of the manifold may allow flow in two directions. The second inlet / outlet may receive unsuspended particles 213 from the first injector 256 and may also supply unsuspended particles 213 from manifold 240 to the first injector 256. A third inlet / outlet may be in fluid communication with a third manifold conduit 226. The third inlet / outlet of manifold 240 may allow flow in two directions. The third inlet / outlet is operable to receive unsuspended particles 213 from the second injector 258 and to supply unsuspended particles 213 to the second injector 258. The fourth outlet of manifold 240 can supply the carrier fluid 233 and non-suspended particles 213 to delivery conduit 250. For example... Figures 2A-2D As shown, the carrier fluid 233 can entrain non-suspended particles 213 in the manifold 240 and deliver the entrained non-suspended particles 252 (e.g., a homogeneous mixture) to the patient or infusion device.

[0070] like Figures 2A-2D As shown, the first syringe 256 and the second syringe 258 can circulate the non-suspended particles 213 back and forth through the manifold 240. By circulating the non-suspended particles back and forth between the first syringe 256 and the second syringe 258, the non-suspended particles 213 can be uniformly distributed due to their kinetic energy. In some examples, the non-suspended particles 213 can circulate back and forth during a preheating period before the third syringe 254 begins to supply the carrier fluid 233 to the manifold 240. For example, the warm-up period can be approximately 1 second to approximately 5 seconds, approximately 5 seconds to approximately 10 seconds, approximately 10 seconds to approximately 15 seconds, approximately 15 seconds to approximately 20 seconds, approximately 20 seconds to approximately 25 seconds, approximately 25 seconds to approximately 30 seconds, approximately 30 seconds to approximately 35 seconds, approximately 35 seconds to approximately 40 seconds, approximately 40 seconds to approximately 45 seconds, approximately 45 seconds to approximately 50 seconds, approximately 50 seconds to approximately 55 seconds, approximately 55 seconds to approximately 1 minute, approximately 1 minute to approximately 2 minutes, approximately 2 minutes to approximately 3 minutes, approximately 3 minutes to approximately 4 minutes, or approximately 4 minutes to approximately 5 minutes.

[0071] After an optional preheating period, the plunger 232 of the third syringe 254 can begin to be compressed, as... Figures 2A-2DThe movement 234 of the third syringe plunger is shown. Circulating the non-suspended particles 213 between the first syringe 256 and the second syringe 258 includes compressing (e.g., pushing the plunger towards the syringe port) and depressurizing (e.g., pulling the plunger away from the syringe port) the plunger 212 of the first syringe 256 and the plunger 222 of the second syringe 258. Figure 2A As shown, circulation of the non-suspended particles 213 can begin at the first position 201. When circulation of the non-suspended particles 213 begins, the plunger 212 of the first syringe 256 is compressed, as indicated by the first syringe plunger movement 214, thereby reducing the volume of the non-suspended particles 213 in the first syringe 256. The plunger 222 of the second syringe 258 is depressurized, as indicated by the second syringe plunger movement 224. The first syringe plunger movement 214 causes the non-suspended particles 213 to be ejected from the first syringe 256 into the second manifold conduit 216 and manifold 240. Some of the non-suspended particles 213 from the first syringe 256 are entrained in the carrier fluid 233 provided by compressing the plunger 232 of the third syringe 254. The entrained non-suspended particles 252 (e.g., a homogeneous mixture) flow through the delivery conduit 250 to the patient or infusion device. The plunger 222 of the second syringe is depressurized, thereby allowing non-suspended particles 213 not entrained in the carrier fluid 233 to fill the barrel 220 of the second syringe 258 through the third manifold 226.

[0072] In some aspects, the inner diameter of the delivery conduit 250, the viscosity of the carrier fluid 233, the density of the unsustainable particles 213, and the hydrodynamic diameter of the unsustainable particles 213 can be used to determine the critical flow rate for maintaining the unsustainable particles 213 entrained in the carrier fluid 233. Once the critical flow rate for maintaining the unsustainable particles entrained in the carrier fluid 104 is determined, this critical flow rate can be multiplied by the inner diameter of the delivery conduit 250 to determine the required flow rate of the carrier fluid 233 for entraining the unsustainable particles. Using this determined flow rate, the pressure required to achieve the required flow rate of the carrier fluid 233 for entraining the unsustainable particles 213 can be determined, thereby determining the force 234 supplied to the plunger 232 of the third injector 254. In some examples, the carrier fluid flow rate is sufficient to entrain the unsustainable particles 213 in the carrier fluid 233, thereby maintaining a uniform dispersion of the unsustainable particles 213. By entraining the unsustainable particles 213, it is ensured that the unsustainable particles 213 do not settle from the carrier fluid and accumulate on the sidewalls of the conduit. It should be understood that the determination of the critical flow rate and flow rate of the entrained carrier fluid 233 is applicable to all systems and methods disclosed herein.

[0073] In some examples, the critical flow rate for entraining non-suspended particles 213 in physiological saline can be 10 cm / s. In this example, when the critical flow rate for entraining non-suspended particles 213 in physiological saline is 10 cm / s, the required flow rate of the carrier fluid 104 for a delivery catheter 250 with an inner diameter of 0.5 mm is 1.2 mL / min. In another example, the critical flow rate for entraining non-suspended particles 105 in water can be 3 cm / s. In this example, for a delivery catheter with an inner diameter of 1.7 mm, the flow rate of the carrier fluid 104 entraining non-suspended particles 105 can be approximately 4 mL / min. In another example, the flow rate of the carrier fluid 233 can be 6 cm / s. In this example, for a delivery catheter with an inner diameter of 0.5 mm, the flow rate of the carrier fluid 213 entraining non-suspended particles 213 can be approximately 0.66 mL / min. It should be understood that other flow rates can be selected based on the critical flow rate required to carry the non-suspended particles 213 and the inner diameter of the delivery conduit 250.

[0074] like Figures 2B-2C As shown, the first syringe plunger movement 214 can continue until all non-suspended particles 213 have been discharged from the first syringe 256. Figure 2B The second position 202 of the cycle is shown. In the second position 202, the first syringe plunger movement 214 continues to expel unsuspended particles 213 from the first syringe 256. In the second position 202, the second syringe plunger movement 224 continues in a rearward direction, thereby allowing unsuspended particles 213 not entrained in the carrier fluid to fill the barrel 220 of the second syringe 258. In the third position 203, as... Figure 2C As shown, all non-suspended particles 213 have been discharged from the first syringe 256. At the third position 203, all non-suspended particles 213 not entrained in the carrier liquid 233 are located in the barrel 220 of the second syringe 258.

[0075] like Figure 2DAs shown, once all the non-suspended particles 213 have been discharged from the barrel 210 of the first syringe 256, the first syringe plunger movement 214 can be reversed, causing the plunger 212 of the first syringe 256 to begin depressurization. Similarly, the direction of the second syringe plunger movement 224 can be reversed, causing the plunger 222 of the second syringe 258 to begin compression. The volume of the non-suspended particles 213 will be smaller than the original volume of the non-suspended particles because some of the non-suspended particles 213 have been entrained in the carrier fluid 233. The cycle can then continue in essentially the same manner as described above. For example, the second syringe plunger movement 224 can continue in a forward direction until all the non-suspended particles 213 have been discharged from the barrel 220 of the second syringe 258. The first syringe plunger movement 214 can continue in a backward direction to allow a certain volume of non-suspended particles 213 (which were not entrained in the carrier fluid 233 when in the manifold 240) to fill the barrel 210 of the first syringe 256. The circulation of non-suspended particles 213 can continue in essentially the same manner until all non-suspended particles 213 have been entrained in the carrier liquid 233.

[0076] In some aspects, the third syringe plunger movement 234 can be configured to ensure a sufficient flow rate of the carrier fluid 233 to allow entrainment of unsuspended particles 213. In some examples, the combination of the third syringe plunger movement 234 (e.g., compression velocity) and the diameter of the first manifold conduit 236 can provide a sufficient flow rate of the carrier fluid 233 to entrain at least some of the unsuspended particles 213 flowing from the first syringe 256 and the second syringe 258 through the manifold 240. The pressure difference between the flow of the carrier fluid 233 and the flow of unsuspended particles 213 allows some particles to be entrained in the carrier fluid 233 within the manifold 240. This pressure difference allows for the continuous delivery of unsuspended particles 213 to the delivery conduit 250.

[0077] In some examples, the third syringe 254, the first syringe 256, and the second syringe 258 may be motorized and controlled by at least one processor. The syringes may be automatically actuated by the processor (e.g., compression or decompression). The motorized syringes can then provide a constant flow rate of entrained non-suspended particles 252 (e.g., a homogeneous mixture) to the patient or infusion device.

[0078] Figures 5-6A constant delivery rate of entrained non-suspended particles 252 (e.g., a homogeneous mixture) based on the volumes of the first and second syringes is shown. The first syringe volume 504 begins to be completely filled with non-suspended particles 213. The first syringe volume can be about 1 mL to about 10 mL, about 10 mL to about 20 mL, about 20 mL to about 30 mL, about 30 mL to about 40 mL, about 40 mL to about 50 mL, about 50 mL to about 60 mL, about 60 mL to about 70 mL, about 70 mL to about 80 mL, about 80 mL to about 90 mL, or about 90 mL to about 100 mL. In another example, the first syringe volume can be about 5 mL to about 100 mL. Figure 5 In the example shown, the first syringe has a volume of 30 mL. In other examples, different volumes of non-suspended particles 213 can be used. The volume of the second syringe can be the same as that of the first syringe. In some examples, the volume of the third syringe (e.g., the volume of the fluid carrier) can be about 5 mL to about 10 mL, about 10 mL to about 20 mL, about 20 mL to about 30 mL, about 30 mL to about 40 mL, about 40 mL to about 50 mL, about 50 mL to about 60 mL, about 60 mL to about 70 mL, about 70 mL to about 80 mL, about 80 mL to about 90 mL, about 90 mL to about 100 mL, about 100 mL to about 110 mL, about 110 mL to about 120 mL, about 120 mL to about 130 mL, about 130 mL to about 140 mL, about 140 mL to about 150 mL, about 150 mL to about 160 mL, about 160 mL to about 170 mL, about 170 mL to about 180 mL, about 180 mL to about 190 mL, about 190 mL to about 200 mL, or more.

[0079] As the plunger of the first syringe is compressed, as described above, the volume of the first syringe 504 decreases, while the volume of the second syringe 502 increases. When the plunger of the first syringe begins to depressurize, while the plunger of the second syringe begins to compress, the volume of the second syringe 502 decreases, while the volume of the first syringe 504 increases. Figure 5 and Figure 6As shown, the delivered non-suspended particles 500 correspond to a reduction in the total volume between the first and second syringes. This reduction in total volume is due to some non-suspended particles being entrained in the carrier fluid. In some examples, the circulation period (e.g., the time between the syringe's full volume and zero volume) can be approximately 5 seconds to approximately 10 seconds, approximately 10 seconds to approximately 15 seconds, approximately 15 seconds to approximately 20 seconds, approximately 20 seconds to approximately 25 seconds, approximately 25 seconds to approximately 30 seconds, approximately 30 seconds to approximately 35 seconds, approximately 35 seconds to approximately 40 seconds, approximately 40 seconds to approximately 45 seconds, approximately 45 seconds to approximately 50 seconds, approximately 50 seconds to approximately 55 seconds, or approximately 55 seconds to approximately 1 minute.

[0080] In some respects, a processor can be used to determine the critical velocity required for infusion of unsustainable particles entrained in a carrier fluid, as described above. In one example, the processor can communicate with a display to show information related to the administration of unsustainable particles. The display can be a visual display operable to receive input from a user of various parameters (e.g., particle concentration, volume of the unsustainable particles to be administered, mass of the unsustainable particles, particle density, carrier fluid density, carrier fluid viscosity, diameter of the delivery catheter, hydrodynamic diameter of the particles, etc.). The processor can then apply the necessary pressure to the carrier fluid to achieve the critical velocity required to entrain the particles.

[0081] like Figures 3A-3B As shown, a system for controlled delivery of non-suspended particles can be a magnetic stirrer system 300. The magnetic stirrer system 300 may include a magnetic stirrer assembly 350 (e.g., a magnetic rotating element), a syringe having a barrel 102 (e.g., a reservoir) and a plunger 103 (e.g., a pressure source), and an external magnet subassembly 310. The magnetic stirrer system 300 may also include a delivery conduit 114 in fluid communication with the syringe interface 112. The magnetic stirrer assembly 350 may be a stirring mechanism. The syringe barrel 102 may be loaded with a carrier liquid 104 and non-suspended particles 105.

[0082] like Figures 3C-3D As shown, the magnetic stirrer assembly 350 may include a base 358, a magnetic stirring fan 352, a stirring fan magnet 355, a first retaining cover 356, and a second retaining cover 359. The second retaining cover 359 can hold the magnetic stirring fan 352 connected to the base 358. The first retaining cover 356 can be configured to hold the stirring fan magnet 355 within a recess of the magnetic stirring fan 352. Figure 3C The rotation axis 354 of the magnetic stirring fan 352 is shown.

[0083] In some aspects, the magnetic stirring fan 352 can have various shapes. For example, the magnetic stirring fan 352 can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more blades. In some examples, the blades can be evenly spaced apart from each other. In another example, the blades can be unevenly spaced apart from each other (e.g., the space between two blades can be smaller than the space between a third blade). In some examples, the blades can have any shape profile known in the art (e.g., curved, flat, round, etc.). In some examples, the blades can extend from the center of the magnetic stirring fan 352 at an angle. In one example, each blade can extend from the center of the magnetic stirring fan 352 in any direction at an angle of about 10 degrees to about 20 degrees, about 20 degrees to about 30 degrees, about 30 degrees to about 40 degrees, about 40 degrees to about 50 degrees, about 50 degrees to about 60 degrees, about 60 degrees to about 70 degrees, about 70 degrees to about 80 degrees, or about 80 degrees to about 90 degrees.

[0084] like Figures 3A-3B As shown, the magnetic stirrer system 300 may include an external magnet subassembly 310. The external magnet subassembly 310 may include an external magnet having a north pole 312 and a south pole 314. The external magnet can rotate about an external magnet rotation axis 316. The external magnet subassembly 310 can generate a sufficient magnetic field to rotate the magnetic stirring fan 352. The external magnet subassembly 310 may be located near the exterior of the syringe barrel 102. In some examples, the magnetic field can be approximately 25 millitalas (mT) to approximately 50 mT, approximately 50 mT to approximately 75 mT, approximately 75 mT to approximately 100 mT, approximately 100 mT to approximately 125 mT, approximately 125 mT to approximately 150 mT, approximately 150 mT to approximately 175 mT, approximately 175 mT to approximately 200 mT, approximately 200 mT to approximately 225 mT, approximately 225 mT to approximately 250 mT, approximately 250 mT to approximately 275 mT, approximately 275 mT to approximately 300 mT, approximately 300 mT to approximately 325 mT, approximately 325 mT to approximately 350 mT, approximately 350 mT to approximately 375 mT, approximately 375 mT to approximately 400 mT, approximately 400 mT to approximately 425 mT, approximately 425 mT to approximately 450 mT, approximately 450 mT to approximately 475 mT, approximately 475 mT to approximately 475 mT. mT to approximately 500 mT or more.

[0085] A magnetic stirrer assembly 350 may be attached to or placed inside the syringe barrel 102. In some examples, the magnetic stirrer assembly 350 may be attached to the distal portion of the syringe (e.g., near the syringe port 112). In other examples, the magnetic stirrer assembly 350 may be attached to the proximal portion of the syringe (e.g., at the end of the plunger 103 within the barrel 102). In further examples, the magnetic stirrer assembly 350 may have the same diameter as the barrel 102. In one example, the magnetic stirrer assembly 350 may be mounted within the barrel 102 using a friction fit. In another example, the magnetic stirrer assembly 350 may be operable to slide back and forth within the barrel 102. In some examples, more than one magnetic stirrer assembly may be placed within the syringe barrel 102. For example, one magnetic stirrer assembly 350 may be attached to the distal portion of the syringe, while another magnetic stirrer assembly 350 may be attached to the proximal portion of the syringe.

[0086] like Figure 3B As shown, the external magnet subassembly 310 can rotate clockwise as indicated by the rotation arrow 318. Rotation of the external magnet subassembly 310 causes rotation of the magnetic stirring fan 352. Rotation of the magnetic stirring fan 352 causes fluid mixing of the non-suspended particles 105. Fluid mixing of the non-suspended particles results in uniform dispersion of the non-suspended particles 105. In some examples, the rate of change of the magnetic field provided by the rotation of the external magnet subassembly 310 can determine the rate of fluid mixing. In some examples, the rate of change of the magnetic field can be approximately 1 Hz to approximately 2 Hz, approximately 2 Hz to approximately 3 Hz, approximately 3 Hz to approximately 4 Hz, approximately 4 Hz to approximately 5 Hz, approximately 5 Hz to approximately 6 Hz, approximately 6 Hz to approximately 7 Hz, approximately 7 Hz to approximately 8 Hz, approximately 8 Hz to approximately 9 Hz, or approximately 9 Hz to approximately 10 Hz. In another example, the rate of change of the magnetic field can be about 1 Hz to about 10 Hz, about 10 Hz to about 20 Hz, about 20 Hz to about 30 Hz, about 30 Hz to about 40 Hz, about 40 Hz to about 50 Hz, about 50 Hz to about 60 Hz, about 60 Hz to about 70 Hz, about 70 Hz to about 80 Hz, about 80 Hz to about 90 Hz, about 90 Hz to about 100 Hz, or higher. Increasing the rotational speed of the external magnet subassembly 310 increases the rate of change of the magnetic field, thereby increasing the speed of fluid mixing. Decreasing the rotational speed of the external magnet subassembly 310 decreases the rate of change of the magnetic field, thereby decreasing the speed of fluid mixing.

[0087] In another aspect, the external magnet subassembly 310 may be an electrical coil wound around the syringe barrel 102. This electrical coil is operable to provide a magnetic field to rotate the magnetic stirring fan 352. In another example, the electrical coil is operable in place of both the external magnet subassembly 310 and the magnetic stirrer assembly 352. The electrical coil is operable to provide a varying magnetic field to the non-suspended particles 105. When the non-suspended particles 105 are magnetic particles, the magnetic field provided by the electrical coil is operable to uniformly disperse the non-suspended particles 105.

[0088] In some aspects, the non-suspended particles 105 may be agitated before being infused into the delivery conduit 114 to ensure uniform dispersion. This period is referred to as an optional preheating period. For example, the preheating period may be approximately 1 second to approximately 5 seconds, approximately 5 seconds to approximately 10 seconds, approximately 10 seconds to approximately 15 seconds, approximately 15 seconds to approximately 20 seconds, approximately 20 seconds to approximately 25 seconds, approximately 25 seconds to approximately 30 seconds, approximately 30 seconds to approximately 35 seconds, approximately 35 seconds to approximately 40 seconds, approximately 40 seconds to approximately 45 seconds, approximately 45 seconds to approximately 50 seconds, approximately 50 seconds to approximately 55 seconds, approximately 55 seconds to approximately 1 minute, approximately 1 minute to approximately 2 minutes, approximately 2 minutes to approximately 3 minutes, approximately 3 minutes to approximately 4 minutes, or approximately 4 minutes to approximately 5 minutes.

[0089] While the non-suspended particles 105 are uniformly dispersed by the magnetic stirrer assembly 350, the non-suspended particles 105 can be delivered to the delivery conduit 114 by compressing the plunger 103 of the syringe (e.g., by applying force to the plunger 103) (as shown by force 122). In some aspects, the inner diameter of the delivery conduit 114, the viscosity of the carrier fluid 104, the density of the non-suspended particles 105, and the hydrodynamic diameter of the non-suspended particles 105 can determine the critical flow rate for maintaining the non-suspended particles 105 entrained in the carrier fluid. Once the critical flow rate for maintaining the non-suspended particles entrained in the carrier fluid 104 is determined, this critical flow rate can be multiplied by the inner diameter of the delivery conduit 114 to determine the flow rate of the carrier fluid 104 required to entrain the non-suspended particles. Using this determined flow rate, the pressure required to achieve the required flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be determined, thereby determining the force 122 supplied to the plunger 103 of the syringe. In some examples, the carrier fluid flow rate is sufficient to entrain the non-suspended particles 105 within the carrier fluid 104, thereby maintaining a uniform dispersion of the non-suspended particles 105. By entraining the non-suspended particles 105, it is ensured that the non-suspended particles 105 do not settle from the carrier fluid and accumulate on the sidewalls of the pipe. It should be understood that the determination of the critical flow velocity and carrier fluid flow rate for the entrainment carrier fluid 104 is applicable to all systems and methods disclosed herein.

[0090] In some examples, the critical flow rate for entraining the non-suspended particles 105 in physiological saline can be 10 cm / s. In this example, when the critical flow rate for entraining the non-suspended particles 105 in physiological saline is 10 cm / s, the required flow rate of the carrier fluid 104 for a delivery catheter 114 with an inner diameter of 0.5 mm is 1.2 mL / min. In another example, the critical flow rate for entraining the non-suspended particles 105 in water can be 3 cm / s. In this example, for a delivery catheter with an inner diameter of 1.7 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 4 mL / min. In another example, the flow rate of the carrier fluid 104 can be 6 cm / s. In this example, for a delivery catheter with an inner diameter of 0.5 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 0.66 mL / min. It should be understood that other flow rates can be selected based on the critical flow rate required to carry the non-suspended particles 105 and the inner diameter of the delivery conduit 114.

[0091] In another aspect, the non-suspended particles 105 can be uniformly dispersed in the second reservoir. In this example, the non-suspended particles 105 are not placed in the barrel 102 of the syringe 108, but are held in the second reservoir. A magnetic stirrer assembly 350 can be located (e.g., attached to or placed) in the second reservoir. The magnetic stirrer assembly 350 can cause fluid mixing of the non-suspended particles 105 in the second reservoir, thereby uniformly dispersing the non-suspended particles 105 in the second reservoir. The syringe port 112 can be connected to the second reservoir via a tube. By compressing the plunger 103, the carrier fluid 104 can be discharged from the syringe port 112 and enter the tube connecting the syringe to the second reservoir. The non-suspended particles 105 are then infused into the second reservoir by the carrier fluid 104. The carrier fluid 104 enters the second reservoir at a sufficient flow rate so that the fluid-mixed non-suspended particles 105 are infused with the desired uniformity. In other examples, the non-suspended particles 105 can be entrained in the carrier fluid 104 at a desired non-uniform rate. The entrained non-suspended particles 105 can then be delivered to the patient via a delivery conduit 114 in fluid communication with the second reservoir.

[0092] like Figure 4As shown, a system for controlled drug delivery of non-suspended particles can be a peristaltic stirring system 400. The peristaltic stirring system may include a syringe having a barrel 102 (e.g., a liquid reservoir) and a plunger 103 (e.g., a pressure source). The barrel 102 may contain a liquid 104. The liquid 104 may be discharged from a syringe port 112 to deliver the liquid 104 to a peristaltic reservoir 404 (e.g., a fluid circuit). The peristaltic stirring system 400 may include a peristaltic pump 402. The barrel 102 (e.g., a liquid reservoir) may be in fluid communication with the peristaltic reservoir 404 (e.g., a fluid circuit) at one end, and a delivery conduit 410 may be in fluid communication with the peristaltic reservoir 404 at the opposite end.

[0093] like Figure 4 As shown, non-suspended particles 105 can be loaded into the peristaltic reservoir 404. The peristaltic pump 402 can cause the non-suspended particles 105 in the peristaltic reservoir 404 to move in the direction shown by arrow 406. The movement of the non-suspended particles 105 in the peristaltic reservoir 404 can make the non-suspended particles 105 in the peristaltic reservoir 404 uniformly dispersed.

[0094] The carrier fluid 104 can be supplied to the peristaltic reservoir 404 by compressing the plunger 103 (e.g., by applying force to the plunger 103). The carrier fluid 104 can travel to the peristaltic reservoir 404 via the peristaltic reservoir inlet conduit 408. Once the carrier fluid 104 reaches the peristaltic reservoir 404, unsuspended particles 105 can be entrained in the carrier fluid. The entrained unsuspended particles 105 and the carrier fluid can then travel to the patient or infusion device via a delivery conduit 410 in fluid communication with the peristaltic reservoir 404.

[0095] In some aspects, the inner diameter of the delivery conduit 410, the viscosity of the carrier fluid 104, the density of the unsustainable particles 105, and the hydrodynamic diameter of the unsustainable particles 105 can determine the critical flow rate required to keep the unsustainable particles 105 entrained in the carrier fluid. Once the critical flow rate is determined, it can be multiplied by the inner diameter of the delivery conduit 410 to determine the flow rate required for the carrier fluid 104 to entrain the unsustainable particles. Using this determined flow rate, the pressure required to achieve the required flow rate for the carrier fluid 104 to entrain the unsustainable particles 105 can be determined, thereby determining the force 122 supplied to the plunger 103 of the syringe and / or the pressure provided by the peristaltic pump 402. In some examples, the carrier fluid flow rate is sufficient to entrain the unsustainable particles 105 in the carrier fluid 104, thereby maintaining a uniform dispersion of the unsustainable particles 105. By entraining the unsustainable particles 105, it is ensured that the unsustainable particles 105 do not settle from the carrier fluid and accumulate on the sidewalls of the conduit. It should be understood that the determination of the critical flow rate and flow rate of the entrained carrier fluid 104 is applicable to all systems and methods disclosed herein.

[0096] In some examples, the critical flow rate for entraining the non-suspended particles 105 in physiological saline can be 10 cm / s. In this example, when the critical flow rate for entraining the non-suspended particles 105 in physiological saline is 10 cm / s, the required flow rate of the carrier fluid 104 for a delivery catheter 410 with an inner diameter of 0.5 mm is 1.2 mL / min. In another example, the critical flow rate for entraining the non-suspended particles 105 in water can be 3 cm / s. In this example, for a delivery catheter with an inner diameter of 1.7 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 4 mL / min. In another example, the flow rate of the carrier fluid 104 can be 6 cm / s. In this example, for a delivery catheter with an inner diameter of 0.5 mm, the flow rate of the carrier fluid 104 entraining the non-suspended particles 105 can be approximately 0.66 mL / min. It should be understood that other flow rates can be selected based on the critical flow rate required to carry the non-suspended particles 105 and the inner diameter of the delivery conduit 410.

[0097] In another aspect, all systems 100, 200, 300, and 400 described herein can be controlled by a processor. The processor can automate the delivery of non-suspended particles by automating the actuation of the stirring mechanisms (e.g., rocker plates, circulating syringe systems, magnetic stirrer assemblies, and peristaltic pumps) and infusion mechanisms (e.g., infusion syringe plungers) described herein. It should be understood that the syringes described herein can be replaced by equivalent systems known in the art. For example, a reservoir and pump system can be used in place of or in combination with the syringes described herein. In some examples, the reservoir can be a vial, syringe barrel, or any type of container.

[0098] This document also describes a method for controlled drug delivery of non-suspended particles. This method can use the system described herein to deliver uniformly defined non-suspended particles. In other examples, the method can use the system described herein to deliver non-suspended particles in a desired non-uniformly dispersed state. Figure 7 A method 700 for controlled administration of non-suspended particles is shown.

[0099] At block 702, the method may include providing a plurality of non-suspended particles to at least one reservoir. The at least one reservoir may be the barrel of a syringe as described herein. In another example, the plurality of non-suspended particles may be placed in a reservoir of another type (e.g., a second reservoir) as described herein.

[0100] At box 704, the method may include agitating non-suspended particles in at least one reservoir via a stirring mechanism. In some examples, as described herein, the stirring mechanism may be a rocker, a circulation mechanism (e.g., two syringes), a magnetic stirrer assembly, or a peristaltic pump. The stirring mechanism may be operable to uniformly or non-uniformly disperse a plurality of non-suspended particles.

[0101] In block 706, the method may include entraining non-suspended particles in a carrier fluid. The conduits and tubing described herein can be used to entrain non-suspended particles in the carrier fluid.

[0102] At box 708, the method may include delivering non-suspended particles entrained in a carrier fluid to a patient or infusion device. The non-suspended particles entrained in the carrier fluid may be delivered to the patient or infusion device via the delivery catheter described herein. In some examples, the non-suspended particles may be delivered in a uniformly dispersed manner. In other examples, non-suspended particles in a desired non-uniformly dispersed state may be delivered.

[0103] Example

[0104] In the first example, using Figures 2A-2D A mechanical stirring system 200 is used to deliver the non-suspended particles. The circulation period is 30 seconds (e.g., including the time it takes for the first syringe to change from full volume to zero volume within the barrel). 30 mL of non-suspended particles are infused over 5 minutes. Figure 5 The conveying rate 500 of the entrained non-suspended particles is shown, as well as the syringe volume 504 of the first syringe and the syringe volume 502 of the second syringe.

[0105] exist Figure 6 In the second example shown, using Figures 2A-2C A mechanical stirring system 200 delivers iron oxide nanoparticles (INOP) to the patient. The INOP volume is 30 mL. The INOP concentration is 16.7 mg / mL. The circulation period is 30 seconds (e.g., including the time it takes for the first syringe to go from a 30 mL volume to zero). The total mass of INOP delivered is 450 mg. The equivalent INOP volume is 27 mL. The infusion time is 15 minutes. The carrier fluid is normal saline. The carrier fluid volume is 200 mL. The total volume of normal saline administered is 173 mL. The flow rate of normal saline is 11.53 mL / min. The flow rate of INOP during the infusion duration is 30 mg / mL. The infusion rate of non-suspended particles entrained in the saline is 13.3 mL / min. Figure 6 The figure shows the delivery rate 500 of the entrained non-suspended particles, as well as the syringe volume 504 of the first syringe and the syringe volume 502 of the second syringe.

[0106] The disclosures shown and described above are merely examples. While many features and advantages of the present technology, as well as details of the structure and function of the invention, have been set forth in the foregoing description, the invention is illustrative only, and changes to details may be made to the maximum extent indicated by the broad meaning of the terms used in the appended claims, particularly in terms of shape, size, and arrangement of components, within the principles of the invention. Therefore, it should be understood that the above examples can be modified within the scope of the appended claims.

[0107] Exemplary Implementation

[0108] The following is a list of non-limiting exemplary implementations, and combinations thereof may be included.

[0109] Implementation 1: A system for controlled delivery of non-suspended particles, the system comprising: at least one reservoir operable to contain a plurality of non-suspended particles and / or a carrier fluid; a stirring mechanism operable to stir the non-suspended particles in the at least one reservoir; and a delivery conduit in fluid communication with the at least one reservoir.

[0110] Implementation Method 2: The system as described in Implementation Method 1, wherein the stirring mechanism provides mechanical stirring for the non-suspended particles to uniformly disperse the plurality of non-suspended particles.

[0111] Implementation 3: The system as described in Implementation 1, wherein the at least one reservoir is the barrel of a syringe.

[0112] Implementation 4: The system as described in Implementation 3, wherein the syringe further includes a plunger operable to discharge the plurality of unsuspended particles and / or the carrier fluid from the barrel into the delivery conduit.

[0113] Implementation method 5: The system as described in implementation method 4, wherein the stirring mechanism is a rocker plate connected to the cylinder.

[0114] Embodiment 6: The system as described in Embodiment 5 further includes one or more agitators within the barrel of the syringe.

[0115] Implementation 7: The system as described in Implementation 6, wherein the rocker stirs the one or more stirring bodies, thereby mechanically and uniformly dispersing the non-suspended particles in the cylinder.

[0116] Implementation method 8: The system as described in implementation method 7, wherein the stirring mechanism is a circulation mechanism.

[0117] Implementation 9: The system as described in Implementation 8, wherein the circulation mechanism includes a first syringe having a barrel and a plunger, and a second syringe having a barrel and a plunger, wherein the first syringe and the second syringe are in fluid communication.

[0118] Embodiment 10: The system as described in Embodiment 9 further includes a third syringe having a barrel and a plunger, wherein the barrel of the third syringe is the at least one reservoir containing the carrier liquid.

[0119] Implementation 11: The system as described in Implementation 10, wherein the barrels of the first syringe and the barrels of the second syringe contain the non-suspended particles.

[0120] Implementation 12: The system as described in Implementation 11 further includes a manifold in fluid communication with the first syringe, the second syringe, the third syringe, and the delivery conduit.

[0121] Implementation 13: The system as described in Implementation 12, wherein the plunger of the first syringe and the plunger of the second syringe are operable to compress and / or depressurize to allow the unsuspended particles to circulate between the first syringe and the second syringe through the manifold, thereby mechanically and uniformly dispersing the unsuspended particles.

[0122] Embodiment 14: The system as described in Embodiment 13, wherein the plunger of the third syringe is operable to be compressed and discharge the carrier fluid into the manifold.

[0123] Implementation 15: The system as described in Implementation 14, wherein the carrier fluid in the manifold entrains some of the plurality of non-suspended particles, thereby providing the entrained non-suspended particles to the delivery conduit.

[0124] Implementation 16: The system as described in Implementation 1, wherein the stirring mechanism is a magnetic stirrer assembly.

[0125] Embodiment 17: The system as described in Embodiment 16, wherein the magnetic stirrer assembly includes a magnetic stirrer fan.

[0126] Embodiment 18: The system as described in Embodiment 17, wherein the at least one reservoir comprises a syringe having a barrel and a plunger.

[0127] Embodiment 19: The system as described in Embodiment 18, wherein the magnetic stirrer assembly is coupled to the interior of the syringe barrel.

[0128] Implementation 20: The system as described in Implementation 19 further includes an external magnet subassembly configured to rotate to cause a change in the magnetic field operable to rotate the magnetic stirrer fan.

[0129] Implementation 21: The system as described in Implementation 20, wherein the rotation of the magnetic stirrer fan mechanically and uniformly disperses the non-suspended particles in the syringe barrel.

[0130] Implementation 22: The system as described in Implementation 21, wherein the plunger is operable to discharge uniformly dispersed non-suspended particles and the carrier fluid into the delivery conduit.

[0131] Implementation method 23: The system as described in implementation method 1, wherein the stirring mechanism is a peristaltic pump.

[0132] Implementation 24: The system as described in Implementation 23, wherein the carrier liquid is in the at least one reservoir and the non-suspended particles are in a peristaltic reservoir.

[0133] Implementation 25: The system as described in Implementation 24, wherein the peristaltic pump provides pressure to the non-suspended particles in the peristaltic reservoir, thereby causing the non-suspended particles to be uniformly dispersed.

[0134] Embodiment 26: The system as described in Embodiment 25, wherein the at least one reservoir is a syringe having a barrel and a plunger in fluid communication with the peristaltic reservoir.

[0135] Implementation 27: The system as described in Implementation 26, wherein the plunger is operable to provide the carrier fluid to the peristaltic reservoir and entrain the uniformly dispersed non-suspended particles.

[0136] Implementation 28: The system as described in Implementation 27, wherein the peristaltic reservoir is in fluid communication with the delivery conduit.

[0137] Implementation 29: The system as described in Implementation 28, wherein the carrier fluid and the entrained non-suspended particles are delivered to the delivery conduit by pressure provided by the peristaltic pump.

[0138] Implementation Method 30: The system as described in Implementation Method 1, wherein the non-suspended particles are magnetic nanoparticles and the carrier liquid is physiological saline.

[0139] Embodiment 31: A system for controlled delivery of non-suspended particles, the system comprising: at least one reservoir containing a plurality of non-suspended particles, a carrier fluid, and one or more agitators; a stirring mechanism operable to mechanically agitate the one or more agitators to uniformly disperse the plurality of non-suspended particles; and a delivery conduit in fluid communication with the at least one reservoir, operable to deliver the uniformly dispersed non-suspended particles and the carrier fluid to a patient; wherein the stirring mechanism is a rocker connected to the at least one reservoir.

[0140] Embodiment 32: A system for controlled delivery of non-suspended particles, the system comprising: a first reservoir and a second reservoir containing a plurality of non-suspended particles, the first reservoir and the second reservoir being in fluid communication with a manifold; a third reservoir containing a carrier fluid, the third reservoir being in fluid communication with the manifold; and a delivery conduit in fluid communication with the manifold; wherein the non-suspended particles circulate between the first reservoir and the second reservoir by means of a pressure source, thereby uniformly dispersing the plurality of non-suspended particles; wherein the carrier fluid is discharged from the third reservoir, entraining some of the plurality of non-suspended particles in the manifold; and wherein the non-suspended particles entrained in the carrier fluid are delivered to a patient via the delivery conduit.

[0141] Embodiment 33: A system for controlled delivery of non-suspended particles, the system comprising: at least one reservoir containing a plurality of non-suspended particles and a carrier fluid; a magnetic stirrer fan assembly coupled within the at least one reservoir; an external magnet assembly located near the exterior of the at least one reservoir; and a delivery conduit in fluid communication with the at least one reservoir; wherein rotation of the external magnet assembly causes rotation of the magnetic stirrer fan; wherein rotation of the magnetic stirrer fan assembly causes fluid mixing of the plurality of non-suspended particles in the at least one reservoir; wherein the fluid-mixed non-suspended particles and the carrier fluid are discharged from the at least one reservoir to the delivery conduit by means of a pressure source.

[0142] Embodiment 34: A system for controlled delivery of non-suspended particles, the system comprising: a first reservoir containing a carrier fluid, the first reservoir being in fluid communication with a peristaltic reservoir containing a plurality of non-suspended particles; a peristaltic pump in fluid communication with the peristaltic reservoir, the peristaltic pump being operable to provide pressure to the peristaltic reservoir to uniformly disperse the plurality of non-suspended particles; and a delivery conduit in fluid communication with the peristaltic reservoir; wherein the carrier fluid is provided to the peristaltic reservoir by means of a pressure source; wherein the carrier fluid entrains the non-suspended particles in the peristaltic reservoir; and wherein the carrier fluid and the non-suspended particles are provided to the delivery conduit by means of pressure provided by the peristaltic pump.

[0143] Implementation 35: A method for controlled administration of non-suspended particles, the method comprising: providing a plurality of non-suspended particles to at least one reservoir; agitating the plurality of non-suspended particles in the at least one reservoir via a stirring mechanism; entraining the plurality of non-suspended particles in a carrier fluid; and delivering the plurality of non-suspended particles entrained in the carrier fluid to a patient or infusion device via a delivery conduit.

[0144] Embodiment 36: A system for controlled administration of non-suspended particles to a patient, comprising: at least one reservoir, the at least one reservoir containing the non-suspended particles in a carrier fluid at least before completely administering the non-suspended particles to the patient; a stirrer configured to agitate the non-suspended particles in the carrier fluid to dispense the non-suspended particles within the at least one reservoir, wherein the stirrer includes one of: i) a reciprocating plate coupled to the at least one reservoir and configured to reciprocate the at least one reservoir, ii) a reciprocating plate configured to reciprocate within the at least one reservoir. The system comprises: a circulation mechanism for circulating the unsuspended particles in the carrier fluid within the container; and iii) a magnetic stirring system configured to alter the magnetic field surrounding the at least one reservoir containing the unsuspended particles in the carrier fluid; a delivery tube fluidly connected to the at least one reservoir and configured to receive a homogeneous mixture of the unsuspended particles in the carrier fluid for controlled administration of the unsuspended particles to the patient; and a pressure mechanism fluidly connected to the at least one reservoir and configured to guide the homogeneous mixture of the unsuspended particles in the carrier fluid into the delivery tube.

[0145] Implementation method 37: The system as described in implementation method 36, wherein the non-suspended particles are nanoparticles.

[0146] Implementation method 38: The system as described in implementation method 37, wherein the nanoparticles are magnetic nanoparticles.

[0147] Embodiment 39: The system as described in Embodiment 36, wherein the stirrer includes a reciprocating plate coupled to the at least one reservoir and configured to reciprocate the at least one reservoir.

[0148] Implementation 40: The system as described in Implementation 39, wherein only one reservoir is provided to contain the non-suspended particles in the carrier liquid.

[0149] Embodiment 41: The system as described in Embodiment 40, wherein the at least one reservoir is formed as a cylindrical body.

[0150] Implementation 42: The system as described in Implementation 41, wherein the pressure mechanism is a linearly movable plunger received within one end of the cylindrical body.

[0151] Implementation method 43: The system as described in implementation method 42, wherein the delivery pipe is connected to the interface of the cylindrical body.

[0152] Embodiment 44: The system as described in Embodiment 43 further includes a stirring element held within the cylindrical body.

[0153] Embodiment 45: The system as described in Embodiment 36, wherein the agitator includes a circulation mechanism configured to circulate the non-suspended particles in the carrier liquid within the at least one reservoir.

[0154] Embodiment 46: The system as described in Embodiment 45, wherein two reservoirs are provided that contain the non-suspended particles in the carrier liquid and are fluidly connected to each other.

[0155] Implementation 47: The system as described in Implementation 46, wherein the circulation mechanism includes two linearly movable plungers, each plunger being received at one end of a reservoir containing the non-suspended particles in the carrier fluid.

[0156] Implementation 48: The system as described in Implementation 47, wherein the pressure mechanism includes a liquid reservoir and a linearly movable plunger received in one end of the liquid reservoir.

[0157] Embodiment 49: The system as described in Embodiment 48, wherein the at least one reservoir containing the unsuspended particles within the carrier fluid stirrer includes a fluid loop, and the circulation mechanism is configured to circulate the unsuspended particles within the carrier fluid around the fluid loop.

[0158] Implementation 50: The system as described in Implementation 49, wherein the fluid loop is formed by a pipe and the circulation mechanism is a peristaltic pump.

[0159] Implementation 51: The system as described in Implementation 50, wherein the pressure mechanism includes a liquid reservoir and a linearly movable plunger received in one end of the liquid reservoir.

[0160] Embodiment 52: The system as described in Embodiment 51, wherein the liquid reservoir is connected to one end of the fluid circuit and the delivery pipe is connected to the opposite end of the fluid circuit.

[0161] Implementation 53: The system as described in Implementation 36, wherein the stirrer includes a magnetic stirring system configured to change the magnetic field around the at least one reservoir containing the non-suspended particles in the carrier liquid.

[0162] Embodiment 54: The system as described in Embodiment 53 further includes a magnetic rotating element within the at least one reservoir.

[0163] Implementation method 55: The system as described in implementation method 36, wherein the non-suspended particles are microparticles.

Claims

1. A system for controlled delivery of non-suspended particles, the system comprising: At least one reservoir, said at least one reservoir being operable to contain a plurality of non-suspended particles and / or a carrier liquid; A stirring mechanism, operable to stir the non-suspended particles in the at least one reservoir; as well as A delivery conduit, which is in fluid communication with the at least one reservoir.

2. The system as claimed in claim 1, wherein, The stirring mechanism provides mechanical stirring for the non-suspended particles to uniformly disperse the plurality of non-suspended particles.

3. The system as described in claim 1, wherein, The at least one reservoir is the barrel of a syringe.

4. The system as described in claim 3, wherein, The syringe also includes a plunger operable to discharge the plurality of non-suspended particles and / or the carrier fluid from the barrel into the delivery conduit.

5. The system as described in claim 4, wherein, The stirring mechanism is a rocker plate connected to the cylinder.

6. The system of claim 5, further comprising one or more agitators within the barrel of the syringe.

7. The system of claim 6, wherein, The rocker plate stirs the one or more stirring bodies, thereby mechanically and uniformly dispersing the non-suspended particles in the cylinder.

8. The system of claim 7, wherein, The stirring mechanism is a circulation mechanism.

9. The system of claim 8, wherein, The circulation mechanism includes a first syringe having a barrel and a plunger, and a second syringe having a barrel and a plunger, wherein the first syringe and the second syringe are in fluid communication.

10. The system of claim 9, further comprising a third syringe having a barrel and a plunger, wherein, The barrel of the third syringe is the at least one reservoir that contains the carrier liquid.

11. The system of claim 10, wherein, The barrels of the first syringe and the second syringe contain the plurality of non-suspended particles.

12. The system of claim 11, further comprising a manifold in fluid communication with the first syringe, the second syringe, the third syringe, and the delivery conduit.

13. The system of claim 12, wherein, The plungers of the first syringe and the second syringe are operable to compress and / or depressurize to allow the unsuspended particles to circulate between the first and second syringes through the manifold, thereby mechanically and uniformly dispersing the unsuspended particles.

14. The system of claim 13, wherein, The plunger of the third syringe is operable to be compressed and discharge the carrier fluid into the manifold.

15. The system of claim 14, wherein, The carrier fluid in the manifold entrains some of the multiple non-suspended particles, thereby providing the entrained non-suspended particles to the delivery conduit.

16. The system of claim 1, wherein, The stirring mechanism is a magnetic stirrer assembly.

17. The system of claim 16, wherein, The magnetic stirrer assembly includes a magnetic stirrer fan.

18. The system of claim 17, wherein, The at least one reservoir includes a syringe having a barrel and a plunger.

19. The system of claim 18, wherein, The magnetic stirrer assembly is connected to the interior of the syringe barrel.

20. The system of claim 19, further comprising an external magnet subassembly configured to rotate to cause a change in the magnetic field operable to rotate the magnetic stirrer fan.

21. The system of claim 20, wherein, The rotation of the magnetic stirrer fan mechanically and uniformly disperses the non-suspended particles in the syringe barrel.

22. The system of claim 21, wherein, The plunger is operable to discharge the uniformly dispersed non-suspended particles and the carrier fluid into the delivery conduit.

23. The system of claim 1, wherein, The stirring mechanism is a peristaltic pump.

24. The system of claim 23, wherein, The carrier fluid is in at least one reservoir, and the non-suspended particles are in a peristaltic reservoir.

25. The system of claim 24, wherein, The peristaltic pump applies pressure to the non-suspended particles in the peristaltic reservoir, thereby dispersing the non-suspended particles uniformly.

26. The system of claim 25, wherein, The at least one reservoir is a syringe with a cylinder and a plunger that is in fluid communication with the peristaltic reservoir.

27. The system of claim 26, wherein, The plunger is operable to supply the carrier fluid to the peristaltic reservoir and entrain the uniformly dispersed non-suspended particles.

28. The system of claim 27, wherein, The peristaltic reservoir is in fluid communication with the delivery conduit.

29. The system of claim 28, wherein, The carrier fluid and the entrained non-suspended particles are delivered to the delivery conduit by pressure provided by the peristaltic pump.

30. The system of claim 1, wherein, The non-suspended particles are magnetic nanoparticles, and the carrier liquid is physiological saline.

31. A system for controlled delivery of non-suspended particles, the system comprising: At least one reservoir, the at least one reservoir containing a plurality of non-suspended particles, a carrier liquid, and one or more agitators; A stirring mechanism, operable to mechanically stir one or more stirring bodies, thereby uniformly dispersing the plurality of non-suspended particles; as well as A delivery catheter in fluid communication with the at least one reservoir, the delivery catheter being operable to deliver the uniformly dispersed non-suspended particles and the carrier fluid to the patient; The stirring mechanism is a rocker plate connected to the at least one liquid reservoir.

32. A system for controlled delivery of non-suspended particles, the system comprising: A first reservoir and a second reservoir that contain multiple non-suspended particles, the first reservoir and the second reservoir being in fluid communication, and the first reservoir and the second reservoir being in fluid communication with a manifold; A third reservoir for containing a carrier fluid, the third reservoir being in fluid communication with the manifold; A delivery conduit in fluid communication with the manifold; The plurality of non-suspended particles are circulated between the first reservoir and the second reservoir by means of a pressure source through the manifold, thereby uniformly dispersing the plurality of non-suspended particles; The carrier liquid is discharged from the third reservoir by means of a second pressure source, and carries some of the non-suspended particles among the plurality of non-suspended particles passing through the manifold. The non-suspended particles entrained in the carrier fluid are delivered to the patient via the delivery catheter.

33. A system for controlled delivery of non-suspended particles, the system comprising: At least one reservoir, the at least one reservoir containing a plurality of non-suspended particles and a carrier liquid; A magnetic stirrer fan assembly, the magnetic stirrer fan assembly including a magnetic stirrer fan, the magnetic stirrer fan assembly being connected within the at least one reservoir; An external magnet assembly, the external magnet assembly being located near the exterior of the at least one reservoir; as well as A delivery conduit in fluid communication with the at least one reservoir; The rotation of the external magnet assembly causes the magnetic stirrer fan to rotate; The rotation of the magnetic stirrer fan assembly causes fluid mixing of the plurality of non-suspended particles in the at least one reservoir; The non-suspended particles in the fluid mixture are uniformly dispersed in the carrier liquid; The uniformly dispersed non-suspended particles and the carrier liquid are discharged from the at least one reservoir to the delivery conduit by means of a pressure source.

34. A system for controlled delivery of non-suspended particles, the system comprising: A first reservoir containing a carrier liquid, the first reservoir being in fluid communication with a peristaltic reservoir containing a plurality of non-suspended particles; A peristaltic pump in fluid communication with the peristaltic reservoir, the peristaltic pump being operable to provide pressure to the peristaltic reservoir, thereby uniformly dispersing the plurality of non-suspended particles; as well as A delivery conduit in fluid communication with the peristaltic reservoir; The carrier fluid is supplied to the peristaltic reservoir by means of a pressure source; The carrier fluid entrains the non-suspended particles in the peristaltic reservoir; The carrier fluid and the entrained non-suspended particles are supplied to the delivery conduit by means of pressure provided by the peristaltic pump.

35. A method for controlled delivery of non-suspended particles, the method comprising: Provide multiple non-suspended particles to at least one reservoir; The plurality of non-suspended particles in the at least one reservoir are stirred by a stirring mechanism; The plurality of non-suspended particles are entrained in the carrier liquid; as well as The plurality of non-suspended particles entrained in the carrier fluid are delivered to the patient or infusion device via a delivery catheter.

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