Abstract: Embodiments of the present disclosure related to system and method for displacing or transporting a collection of particles of a substance from a first location to a second location. An embodiment of the present disclosure includes forming a suspension of a substance, wherein the suspension may be in a colloidal state. In an embodiment the first location is proximate to the intended target location. In an embodiment, the suspension of the substance is inserted into a medium, wherein the medium is a transport medium for the suspension of the substance. In an embodiment, the suspension of the substance possesses magnetic properties. In an embodiment, to transport the substance from the first location to the intended target location, the substance in that is the form of a suspension, colloidal state, includes a collection of particles. In an embodiment the collection of particles may be grouped to form a cluster. In an embodiment, in a three-dimensional space of the cluster, a gradient magnetic field may be provided along a two-dimensional (2D) (XY) plane and a pulsating magnetic field may be provided along a third axis (z-axis), wherein the gradient magnetic field along the 2D plane in conjunction with the pulsating magnetic field along the third-axis in conjunction displaces the cluster from a first position to a second position, thereby transporting the cluster to the intended target location. In an embodiment, the degree of clustering and the displacement of the clusters are strongly dependent on the surface properties of the particles, implying any modification of the surface property due to conjugation with a chemical moiety present within the suspension can be detected. Other embodiments are also disclosed.
Description:DISCLAIMER
[0001] Portions of this patent document may contain material that may be subject to copyright OR Trademark protection. The owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office file or records, but otherwise reserves all copyright rights and trademarks whatsoever. All copyrights and trademarks are owned by Indian Institute of Science, Bangalore.
TECHNICAL FIELD
[0002] This disclosure relates generally to clustering and motility of colloidal suspensions in a medium, and particularly to transportation of substance in a colloidal state from a first location to an intended target location in the medium.
BACKGROUND
[0003] Current research and progress in the field of nanoscience and engineering have come up with concepts like self-assembly, transport and manipulation of matter that have been taking the center stage. Advancement in nanotechnology has had a positive impact in the biological world for example, in the field of drug delivery, which has resulted in opening new field of research for precision diagnostics and therapeutics. For example, in the field of nanotechnology and associated research, currently research is focused on micro and nano robots (also referred to as microparticles or micromaterials and nanomaterials or nanoparticles) that are moving around in complex media, which are specifically intended for performing tasks by a method of transporting these micro and nano robots to a desired location, which may also include the field of diagnostics, therapeutics and treatments. The motility of such micro and nano scaled objects is a challenge both in terms of their design and the way they are controlled in a medium where they are transported.
[0004] However, there are several challenges in realizing the potential of such nano materials such as their design, control and movement in the medium. Synthesizing nano particles may have become more efficient and easier, but the tools to control these nano particles are still in their nascent stages. For example, nano robotics is one such domain where transport is a main action required and the transportation of these nano robots needs to be in a precise, efficient, and controlled manner. Current technologies suffer from this setback, which becomes a hurdle to implement these technologies. A variety of energy sources may be used to transport and energize such systems with nanorobots such as electric fields, chemical reactions, magnetic fields, light, enzymes etc. However, challenges galore for instance, the motility of these nano robots, which need to be compatible with the medium and/or shouldn’t alter the physical or chemical properties of the nano materials. Yet another obstacle is observed in such an environment having a Low Reynolds number where viscosity dominates or plays a critical role in the transportation of the nano robots. It is an object of the present disclosure to ameliorate these disadvantages by transporting these nanorobots to a desired or identified location.
SUMMARY
[0005] Embodiments of the present disclosure related to system and method for displacing or transporting a cluster, wherein the cluster is formed by a collection of particles of a substance or compound, from a first location to a second location, wherein the second location may be a intended target location. An embodiment of the present disclosure includes forming a suspension of a substance or compound by mixing the substance with an appropriate fluid. The suspension thus formed may be in a be in a colloidal state. In an embodiment the suspension is inserted into the medium or object where it is required to be transported at the first location, which will be proximate or close to the intended target location. In an embodiment, the suspension of the substance possesses magnetic properties. In an embodiment, the substance which is in the form of a suspension, colloidal state, includes a collection of particles, which forms a cluster. In an embodiment, in a three-dimensional space, in which the cluster is present, a gradient magnetic field may be provided along a two-dimensional (2D) (XY) plane and a pulsating magnetic field may be provided along a third axis (z-axis), wherein the gradient magnetic field along the 2D plane in conjunction with the pulsating magnetic field along the third-axis displaces the cluster from a first position to a second position, thereby transporting the cluster to the intended target location. In an embodiment, the degree of clustering and the displacement of the clusters may be strongly dependent on the surface properties of the particles, implying any modification of the surface property due to conjugation with a chemical moiety present within the suspension can be detected. Other embodiments are also disclosed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] For a better understanding of the nature and desired objects of the present disclosure, reference is made to the following detailed description taken in conjunction with the accompanying drawing figures wherein like reference character/numerals denote corresponding parts throughout the several views. Objects, features, and advantages of embodiments disclosed herein may be better understood by referring to the following description in conjunction with the accompanying drawings. The drawings are not meant to limit the scope of the claims included herewith. For clarity, not every element may be labeled in every Figure. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments, principles, and concepts. Thus, features and advantages of the present disclosure will become more apparent from the following detailed description of exemplary embodiments thereof taken in conjunction with the accompanying drawings in which:
[0007] Figure 1A illustrates an exemplary schematic of a collection of particles in a medium;
[0008] Figure 1B illustrates another exemplary view of a collection of particles in a medium of a substance dissolved in a fluid creating a colloidal suspension;
[0009] Figure 2 illustrates an exemplary view of clusters of different sizes formed by a collection of particles when the suspension is in a medium in the presence of a magnetic field;
[0010] Figure 3A illustrates an exemplary embodiment of grouping a collection of particles to form a cluster and disassociating the cluster forming a collection of particles by application of a magnetic field (BZ) along a particular axis;
[0011] Figure 3B illustrates an exemplary schematic view of a collection of particles in the absence of the magnetic field (A) and the grouping of a collection of particle in the presence of a magnetic field forming a clusters(B);
[0012] Figure 3C illustrates (A) schematic explaining a simulation model where two colloidal particles lie at the origin and the other at the perimeter of the circle, (B) the simulation shows that there is a net enhancement in the force experienced by the colloids along X and Z directions due to the interactions between the particles, and (C) the simulation shows that there is a net enhancement in the force experienced by the colloids along X and Z directions due to the interactions between the particles;
[0013] Figure 3D illustrates in (A) and (B) the comparative velocities of a single colloid and cluster when the gradient field is in X and Y direction respectively;
[0014] Figure 4A illustrates an exemplary schematic of the displacement of a single cluster from a first position to a second position by using a pulsating magnetic field along the Z-axis and a gradient magnetic field along the XY-plane;
[0015] Figure 4B illustrates particle formed in a cluster with a receptor, wherein a larger receptor increases the size and mass of the particles and the cluster whereas smaller size receptors do not substantially increase the size and mass of the particle or the cluster;
[0016] Figure 5A illustrates an exemplary method of forming a suspension of a substance and inserting the suspension into a medium;
[0017] Figure 5B illustrates an exemplary method of forming a cluster in a medium; and
[0018] Figure 5C illustrates an exemplary method for delivering the cluster to a target location.
DETAILED DESCRIPTION
[0019] Hereinafter, various exemplary embodiments of the present disclosure will be described with reference to the accompanying drawings, where it should be understood that all these drawings and description are only presented as exemplary embodiments. It is to be noted that based on the subsequent description, several alternative embodiments may be conceived that may have a structure similar to that disclosed herein and/or formed by a method as disclosed herein, and all such alternative embodiments may be used without departing from the principle of the disclosure as claimed herein, and hence such alternative embodiments are construed to fall within the scope of the present disclosure.
[0020] All references in the specification made to “one embodiment,” “an embodiment,” “a preferred embodiment” etc., indicate that the embodiment described herein may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases may not be necessarily referring to the same embodiment. It should also be understood that various terminology used herein is for the purpose of describing a particular embodiment or specific embodiments only and the use of such terminology is not intended to be limiting the scope and spirit of the present disclosure. As used herein, the singular forms “a,” “an” and “the” may also include the plural forms, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “has” and “including” used herein, specify the presence of stated features, elements, and/or components etc., but do not preclude the presence of one or more other features, elements, components and/or a combination thereof. For example, the term “multiple” used here indicates “two or more;” the term “and/or” used here may comprise any or all combinations of one or more of the items listed in parallel. Definitions of other terms will be specifically provided in the following description. Furthermore, in the following description, some functions, or structures well-known to those skilled in the art will be omitted in order not to obscure embodiments of the disclosure in the unnecessary details. In the embodiments and claims described herein, reference to a substance may refer to a compound that is being used to form the colloidal suspension of the substance, which may be organic or inorganic or a combination thereof, reference to a medium refers to a channel in which the colloidal suspension may be inserted or placed, and reference to a cluster refers to a collection or particles or a group of particles or a plurality of particles bunched together.
[0021] It may be appreciated that these exemplary embodiments are provided only for enabling those skilled in the art to better understand and then further implement the present disclosure, not intended to limit the scope of the present disclosure in any manner. Besides, in the drawings, for a purpose of illustration, optional steps, modules, and units may be illustrated in dotted-line blocks.
[0022] Embodiments of the present disclosure related to system and method for displacing or transporting a collection of particles of a substance from a first location to a second location, wherein the second location may be a target location. An exemplary embodiment of the present disclosure includes forming a suspension of a substance (substance is also referred generally to as a compound), wherein the substance is diluted in a fluid to form the suspension, and the suspension in an exemplary embodiment may be in a colloidal state consisting of a collection of particles. In an exemplary embodiment the first location is generally proximate to the target location. In an exemplary embodiment, the suspension is formed by an admixture of the substance with a fluid, wherein the fluid may be water or an organic compound or an inorganic compound or a chemical. In an exemplary embodiment, the substance may be a chemical and the fluid may be water. In another exemplary embodiment, the substance may be diluted in water, forming a solution which is in a colloidal state (referred to also as a colloidal solution), and the colloidal solution includes a collection of the particles of the substance in water. In an exemplary embodiment, when the substance is diluted with the fluid, a collection of particles of the substance are dispersed throughout the fluid in a random manner, and the concentration of the particles in the fluid may be controlled by the amount of the substance taken and the amount of fluid in which the substance is dissolved or diluted.
[0023] In an exemplary embodiment, once the suspension of the substance is prepared, which may be in a colloidal state, the suspension is then inserted into a medium, wherein the medium acts as a transportation channel for the suspension to be transported from the first location to the second location. In an exemplary embodiment, the collection of particles in the fluid may possesses magnetic properties and would react to a magnetic field that may be applied from an external source. In an exemplary embodiment the medium may be a Newtonian fluid or a non-Newtonian fluid, which may include at least one of a liquid, a semi-solid or a gel. An example of a Newtonian fluid may be water and an example of a non-Newtonian fluid may be blood or saliva. In an embodiment a collection of particles may be grouped together to form a cluster, wherein each cluster may have a diameter in a range from 1 milli meter to at least 1 nano meter. In another embodiment, each particle of the collection of particles forming the cluster may be having a diameter of 1 milli meter to a few nano meters.
[0024] In an exemplary embodiment, the suspension, also referred to as a collection of particles in the fluid, when inserted into the medium may spread out in a randomly manner around the area of insertion or injection into the medium, and the collection of particles may be configured to first form a cluster, for example where a collection of particles of similar sizes may be grouped together. In an exemplary embodiment, several such clusters may be formed in the medium, wherein each cluster may have particles of a similar size or may have particles of different sizes. In an exemplary embodiment, the first cluster(s) may be formed by applying a constant magnetic field along an axis, for example a magnetic field B may be applied to the medium containing the collection of particles along the z-axis. On application of the Magnetic field BZ, the particles in the medium may form several clusters, wherein each cluster will have a collection of particles. In an exemplary embodiment, other methods of forming a cluster includes and may not be limited to controlling at least one of a pH of the suspension and/or a temperature of the suspension and/or a temperature of the medium. Other techniques to form clusters may be used and all such techniques to form the initial clusters fall within the scope of the present disclosure. In an exemplary embodiment, once the cluster is formed, the cluster is transported or displaced from a first location to an identified location or target location by using a gradient magnetic field in a 2D (XY) plane along the first two axis, in conjunction with a pulsating or oscillating magnetic field along a third (Z) axis.
[0025] In an exemplary embodiment, assuming the gradient magnetic field is applied along the XY plane along the x-axis. In an exemplary embodiment, by applying the gradient magnetic field along the x-axis, BX, a particle moves from a position X to a position Y, wherein the displacement is ΔX, along the direction of the gradient field. The gradient at any point along the x-axis may be represented as Δ BX/ΔX and the force on the particle at that point in may be represented as F = m(ΔBX/ΔX), where F is the force, m is the mass of the particle or the mass of the cluster and ΔBX/ΔX is the gradient. The velocity of the movement of the particle from a first position X to a second position X + ΔX, is proportional to the force at that point in the gradient magnetic field. In an exemplary embodiment, on similar analogy, the force of a cluster, formed by a collection of particles, will be equal to the force on the cluster along the gradient magnetic field at that point. In an exemplary embodiment, the mass in the case of a cluster will be the center of mass of the collection of particles forming the cluster. In an exemplary embodiment, smaller size particles will have a higher velocity and move in the medium at a higher velocity as compared to larger size particles, which will move at a slower velocity because of their size and mass. In an exemplary embodiment, the size of the cluster may depend on the strength of the magnetic field and the size of the particles forming the cluster, and the particle size may affect the clustering efficiency, for example large sized particles may have a bigger distance of separation between the particles than smaller sized particles which may be knit closer together forming a cluster.
[0026] In an exemplary embodiment, consider a suspension to be inserted into a medium. The suspension is formed by taking an object, for example a drug, and forming a colloidal solution by dissolving the object in a liquid medium, for example water. In an exemplary embodiment, the colloidal solution may be made up of a collection of particles and the concentration of the collection of particles may depend on the amount of liquid used for dissolving the object. In an exemplary embodiment, this colloidal solution is then inserted into a target medium, where the collection of particles needs to be transported from a first location to a identified location or a target location. In an exemplary embodiment, the suspension is inserted into the medium, preferably proximate to the first location. In an exemplary embodiment, on insertion of the suspension into the medium, the suspension consisting of a collection of particles is randomly distributed in the medium, i.e., at the first location. In an exemplary embodiment, once inserted into the medium, the suspension may be subjected to a constant magnetic field along the z-axis to form cluster of the particles in the medium. In an exemplary embodiment, clustering of the particles may be performed by other techniques as disclosed previously. In an exemplary case of forming clusters made of particles having magnetic properties, nanometer size clusters may be produced in a magnetic fluid and millimeter size clusters may be produced which for example have been widely used as magnetic brushes in laser printers. In an exemplary embodiment, these clusters made of millimeter size or nanometer size clusters can be formed into stable shapes under a constant magnetic field. In an exemplary embodiment, a colloidal solution of magnetic particles dispersed in a base liquid such as water, hydrocarbon oil and so on may be typically referred to as a magnetic fluid. In an exemplary embodiment. this magnetic fluid has very unique characteristics which is the change of the physical properties by applying an external magnetic field, and when a magnetic field is applied to the magnetic fluid for long time, the inner magnetic particles agglomerate and form a clustering structure in the direction of the magnetic field. In an exemplary embodiment, the clustering structure may have chain-like shape and may grow from time by time after the application of magnetic field.
[0027] In an exemplary embodiment, in a three-dimensional space of the cluster, a gradient magnetic field may be provided along an 2D plane (XY plane, which includes a first axis, the x-axis, and a second axis. the y-axis) and a pulsating magnetic field may be provided along a third axis (the z-axis), wherein the gradient magnetic field in the 2D plane (XY plane) in conjunction with the pulsating magnetic field along the third-axis (z-axis) may be designed to first disassociates the cluster into a collection of particles when the magnetic field is switched to an OFF state, and when the magnetic field is switched to an ON state, the collection of particles that were disassociated are regroup together forming the cluster again. In an exemplary embodiment, when the cluster disassociated and the collection of particles experience a gradient magnetic field along the plane, the particle move in the direction of the gradient with a velocity that is proportional to the gradient of the magnetic field at that point and the size of the particles. The velocity of the particles that are disassociated because of the switching OFF of the magnetic field along the z-axis will be proportional to the force experienced by the particles of the gradient magnetic field in the XY plane. Since the magnetic field is pulsating along the z-axis, when the magnetic field is switched to an ON state, the particle associated again and form the cluster. In this manner by applying a gradient magnetic field along the XY plane and switching ON and OFF the magnetic field along the z-axis, the cluster may be transported from a first position to a target location.
[0028] In an exemplary embodiment, if there are other particles that are closer to the collection to particles when the cluster is disassociated, these other particles may combine with the disassociated particles are proximate to each other to form the cluster when the magnetic field is switched ON forming a larger cluster. In an exemplary embodiment, if there are other non-magnetic particles or impurities or other particles proximate to the disassociated cluster, then when the magnetic field is switched ON along the z-axis, the cluster may split into two or more smaller clusters. In an exemplary embodiment, monitoring the size of the cluster may provide information of impurities present in the medium which may be influencing the motility or transportation of the cluster in the medium. In an exemplary embodiment, impurities may be introduced into the medium to also to perform studies on the medium, for example impurities may be introduced into a suspension to detect whether the targeted location or the medium itself is cancerous or affected by a disease. In an exemplary embodiment, the particles may be attached with an antigen or antibodies and the size of the cluster formed by the particles will depend on the size of the particles and the size of the antigen or antibodies attached, and the velocity of the cluster or the particles will depend and be proportional to the mass of the particle and the antigen together or the cluster formed by the collection of particles and the antigen and/or the antibodies. Further, in another exemplary embodiment, the clustering efficiency may be dependent on the collection of the particles and the attached antigen and/or antibodies and functionality of the cluster may be changed by changing the size of the particle by addition of the antigen and/or antibody. In an exemplary embodiment the antigen and/or antibody may be any other particle required to either change the size of the particle and/or affect the functionality of the particle and/or affect the clustering efficiency of the cluster formed by the collection of particles.
[0029] In an exemplary embodiment, during the disassociation of the cluster and the reformation of the cluster, the particles the particles at a first position X will be move in the direction of the gradient of the magnetic field with a velocity of the particles being directly proportional to the gradient (u α ∇B) at that point. In an exemplary embodiment, this displaces the center of mass of the cluster from the first position X to the next position X + ΔX, where ΔX is the incremental displacement. This phenomenon of switching ON and switching OFF the magnetic field along the z-axis while keeping the gradient magnetic field along the XY plane constant is continued thereby resulting in the displacement the center of mass of the cluster from a first position to a second position and forward until the cluster has reached the target location.
[0030] In an exemplary embodiment, the medium with the suspension may be placed in a 3D magnetic field, where the clusters have already been formed. In an exemplary embodiment, if the cluster have not been formed, a constant magnetic field may be applied along the Z-axis such that the particles in the suspension group together to form clusters, which may either have same size particles or differing size particles. In an exemplary embodiment, switching OFF the magnetic field along the third-axis (z-axis) will dissociate the cluster into particles that are proximate to each other by not in cluster form, and the direction of disassociation of the cluster will be dependent on the gradient of the magnetic field in the 2D plane (XY plane) at that point, as the particles will move along the direction of the gradient of the magnetic field with a velocity that is proportional to the gradient of the magnetic field along the XY plane. The collection of particles will therefore be displaced from a first position to a second position in the absence of the magnetic field in along the z-axis, where the velocity of the collection of particles and the displacement of the collection of particles will be directly proportional to the gradient of the magnetic field. In a further exemplary embodiment, switching ON the magnetic field along the third-axis (z-axis) will regroup the particles that are proximate to each other to form the cluster again. In an exemplary embodiment, the particles may be induced with a memory to remember the cluster formation, such that on switching OFF the magnetic field the cluster disassociated and on switching ON the magnetic field the particles come back together to form the cluster. Because of the switching OFF and ON of the magnetic field along the z-axis and maintaining a gradient magnetic field along the XY plane, the cluster is displaced from a first position X to a second position X + ΔX, where ΔX is the incremental displacement. However, because the disassociation was in the direction and magnitude of the gradient filed along the 2D plane, the center of mass for the cluster moves during the disassociation of the cluster and the reformation or regrouping of the particles to form the cluster. The shift in the center of mass from the position X to X+ ΔX may be directly dependent on the gradient of the magnetic field in the 2D plane at that point. Because the center of mass has for the cluster has shifted by ΔX, the cluster has moved from a first position P1 to a second position P2. This process may be continuously repeated until the cluster reaches the target location.
[0031] In an embodiment, a method for delivering the cluster formed by a collection of particles to a targeted location in an object is disclosed. In an exemplary embodiment, the object may be a human or animal. In an exemplary embodiment a targeted delivery location for the substance may be identified in the object. In an exemplary embodiment, the substance may be a drug. In an exemplary embodiment, a suspension of the substance is formed by dissolving the substance in a liquid, for example water or a fluid, wherein the suspension comprises a colloidal solution having a collection of particles and the collection of particles preferably exhibit magnetic properties. In an exemplary embodiment, the substance may be a chemical and the fluid may be water, wherein mixing the chemical and water in the required proportion provided a suspension of the substance, and the suspension includes a collection of particles of the substance (colloidal solution). The concentration of the suspension can be varied depending on the amount of liquid used for dilution or forming the colloidal solution.
[0032] In a further exemplary embodiment, the suspension of the substance is inserted or injected or provided to an object proximate to a desired target location in a medium, wherein the medium is either one of a Newtonian fluid or a non-Newtonian fluid. In an exemplary embodiment, the substance may be a drug to be delivered to the liver in a living being such as a human or an animal. The drug may be diluted in water, if the drug is water soluble to create a suspension (colloidal solution) of the drug or an appropriate solution may be chosen to dilute the drug to form the colloidal solution. The suspension includes a collection of particles of the drug, which may be preferably in a nano scale domain. In an exemplary embodiment, the suspension may be inserted into the living being, for example a human, proximate to the liver. In an exemplary embodiment, once the suspension is inserted into the object, the suspension containing a collection of particles is randomly distributed and the particles may be configured to form a cluster or several clusters. In an exemplary embodiment, the cluster may be formed by controlling at least one of a pH of the substance and/or a temperature of the substance and/or a temperature of the medium and/or applying a magnetic field to the object. In an exemplary embodiment, every cluster in is a collection of particles. In a preferred embodiment a magnetic field is applied along the z-axis for a defined period of time such that the particles orient themselves in the medium and form clusters. Each cluster formed in the medium may have particles of the same size and/or may include particles of different sizes.
[0033] In an exemplary embodiment, once the first cluster is formed, in a three-dimensional (3D) space of the cluster, a gradient magnetic field is provided along a two-dimensional (XY) plane and a pulsating or oscillating magnetic field is provided along a third axis (z-axis), wherein the gradient magnetic field along the 2D plane in conjunction with the pulsating magnetic field along the third-axis displaces the cluster from a first position to a second position, as disclosed previously. Switching the magnetic field OFF and ON along the third axis, disassociated the cluster into a collection of particles and switching ON the magnetic field along the z-axis regroups the collection of particles that are proximate to each other into a cluster. Because the particle when disassociated move in the direction of the gradient magnetic field, where the smaller size particle move faster than the larger size particle, the center of mass of the cluster is shifted and the cluster is displaced. During the process of disassociation of the cluster and regrouping of the collection of the particles into the cluster, the center of mass of each of the cluster moves along the direction of the gradient of the magnetic field in the 2D (XY) plane, thus displacing the cluster from a first position P1(X) to a second position P2 (X+ ΔX). In an exemplary embodiment, a direction of disassociation of the cluster is directly proportional and dependent of the gradient of the magnetic field at that point in the 2D plane, and the velocity of movement of particles is directly proportional to the force at that point and the size of the particles. In an exemplary embodiment, applying a pulsating magnetic field along the third-axis and providing a gradient magnetic field along the 2D plane may be repeated cyclically until the cluster or clusters reaches the targeted delivery location in the object, i.e., the liver, thereby ensuring that the drug has been safely delivered to the target location.
[0034] Figure 1A illustrates an exemplary schematic of a collection of particles in a medium, which is essentially a substance has been dissolved in a fluid and placed or inserted in a medium. In the exemplary schematic of Figure 1A a collection of particles 120 is shown in a medium 110 along a 2D plane, i.e., for example the a 2D XY plane. A magnetic field B is applied along the third axis, i.e., for example the z-axis. In an exemplary case, the magnetic field BZ applied for a prolonged duration or for a fixed period of time along the z-axis may result in the formation of clusters in the medium. A substance is first dissolved in a fluid (not shown in the figure) to create a suspension, where the suspension will be in a colloidal state, and the concentration of the particles of the substance in the suspension will depend on the amount of fluid that is used for diluting the substance. The suspension in the fluid will consist of a collection of particles 120. The suspension thus formed is then inserted into a medium 110. On inserting the suspension into the medium 110, the suspension locally disperses in the medium 110 in a random manner in a three-dimensional plane, which may depend on the process of insertion. Hence, to organize the collection of particles 120, a constant magnetic field BZ of a pre-determined strength is applied along the third axis for a pre-determined time or for a fixed period, which aligns the particles 120 as the particles 120 possess magnetic properties. It should be obvious to one of ordinary skill in the art that other techniques may also be used to align the collection of particles 120 and form groups or cluster, and all such techniques fall within the scope of the present disclosure. Once the particles are aligned, particles that are proximate to each other can form a group or cluster.
[0035] Figure 1B illustrates another exemplary view of a collection of particles 120 in a medium 110. In Figure 1B a substance was taken and first dissolved in a fluid, for example water. Dissolving the substance in water created a suspension and the distribution of the substance in the water depended on the amount of water used for diluting the substance. The suspension, which essentially is a collection of particles 120 in the fluid, was then inserted/injected into a medium 110, where in this exemplary illustration a liquid medium was used. The medium 110 may be either a Newtonian fluid or a non-Newtonian fluid, and the medium includes at least one of a liquid or a semi-solid or a gel or even include a gaseous medium. In the exemplary case, a Newtonian fluid water was used to create the suspension of the substance. However, it should be obvious to a person of ordinary skill in the art that other Newtonian fluids or non-Newtonian fluids may also be used. An example of a non-Newtonian fluid would be blood.
[0036] The suspension consisting of a collection of particles 120 in the medium 110 is illustrated in Figure 1B. The suspension when inserted in the medium 110 is spread or dispersed over a region of the medium 110, in a random manner, around the region of insertion. Inserting (also referred to as placing or injecting) the suspension into the medium 110 is a localized phenomenon, and in case the medium is large, the suspension cannot spread over the entire medium immediately. After certain time, the suspension may spread over the entire medium 110 due to random motion in a random manner. However, it is imperative that the suspension needs to be delivered to a target location (not shown in Figure), from the point of insertion (not shown in the Figure) in the medium 110. As illustrated, the suspension when inserted into the medium 120 does not have any cluster formation or shows any clustering effects, where a cluster would be defined to include a collection of particles that are grouped together and have a center of mass, wherein each cluster may include particles of the same size or may include particles of different sizes. The suspension may be evenly or unevenly spread over the medium in the local region where it is inserted with a random distribution. In an exemplary embodiment, the motility of the cluster in the medium will depend on the strength of the gradient magnetic field and the size of the particles in the cluster. N an exemplary embodiment, if a cluster has been formed by particles of varying sizes, during the disassociation and regrouping of the particles, the single cluster may be split into multiple clusters because the speed of movement of the particles along the gradient is proportional to the size of the particles. Therefore, smaller particles (in the order of 1 nano meter) would move faster than larger particles (100 milli meter) and the cluster formed by mixed particles sizes may end up forming multiple clusters having particles of different sizes that are uniform, that is particles of 1 nano meter size may form one cluster and particles of 100 millimeter may form another cluster. It should be obvious to a person of ordinary skill in the art that multiple clusters may be formed.
[0037] In an exemplary embodiment, the substance may be a chemical, for example a drug for treating a particular illness, and the fluid used to create the suspension (colloidal state) may be water. The chemical is diluted in water in a certain proportion as required, such that there is sufficient particulate matter in a given or pre-determined amount of fluid, which may depend on the concentration of the suspension required or the concentration of the particulate matter of the substance required. The suspension which includes particles of the dissolved chemical, preferably have a diameter in the range of 1 millimeter to about 1 nanometer or even smaller in size. These are generally referred to as nano robots. These particles in the suspension normally may have different sizes with different diameter in the range of a few millimeters to a few nanometers, and when the suspension is inserted into the medium 110, for example blood or saliva, the particles 120 in the suspension move about with a random motion in the medium 110 as they are not subject to any external force. When these particles are subject to a constant magnetic field along one axis in a three-dimensional place these particles in the medium orient themselves may form clusters by grouping together. For example, particle of a particular size which are proximate to each other may group together forming a cluster or particles of different sizes that are proximate to each other may group together forming a cluster.
[0038] Figure 2 illustrates an exemplary view of a cluster 230 formed by a collection of particles 220 in a medium 210. In one embodiment, once the suspension containing the particles 220 is be inserted into the medium 210, as observed in Figure 1B, and when inserted into the medium 210 the particles 220 will disperse randomly in the medium 210. A cluster or several clusters 230 may be first formed by grouping together a collection of particles that are proximate to each other, and each cluster will include a collection of particles closely and tightly packed together. In an exemplary embodiment, a constant magnetic field BZ is applied along the z-axis to the medium 210 in which the particles 220 are present. The constant magnetic field BZ will orient and align the particles proximate to each other to form a cluster, wherein each cluster may include particles of the same size or may include particles of different sizes. The formation of the cluster would depend on the strength of the magnetic field BZ applied along the z-axis.
[0039] An exemplary cluster 230 formed by applying a constant magnetic field BZ along the z-axis has been magnified and illustrated in Figure 2, which clearly shown a collection of particles closely packed together in a group. Each cluster 230, 230A, 230B, 230C may be of different size in the medium 210 and the diameter of each cluster 230, 230A, 230B, 230C may vary from about 1 millimeter to about 1 nanometer or may be smaller. Each cluster may include particles of the same size or particles of different sizes that are grouped together on application of the magnetic field BZ. After inserting the suspension into the medium 210, a cluster 230 or several clusters 230, 230A, 230B, 230C may be first formed by controlling at least one of a pH of the substance and/or a temperature of the substance and/or a temperature of the medium and/or applying a magnetic field along a fixed axis. In the exemplary case, a constant magnetic field was applied along the z-axis BZ for a predetermined time to form the clusters, where particles proximate to each other oriented and aligned themselves to form a cluster. Several such clusters may be formed. In the exemplary case, when a cluster is formed, all nearby particles 220 are grouped together.
[0040] In the exemplary case illustrated in Figure 2, a constant magnetic field B was applied along a third axis (z-axis) in a three-dimensional (3D) space after the suspension was inserted into the medium. The magnetic field BZ is capable of aligning and orienting the particles proximate to each other, and the particles proximate to each other forms a cluster 230 by grouping the particles together or a group of clusters 230, 203A, 230B, 230C. Each cluster 230 essentially consists of a collection of particles 220, and the number of particles 220 in each cluster vary and the size of the particles in each cluster may vary. The formation of a cluster depends on the number of particles proximate to each other and the strength of the external magnetic field BZ that is applied on the medium 210 containing the particles 220. Once the clusters are formed, the cluster may be transported or displaced from a first location to a second location using the gradient field as will be discussed below.
[0041] In an exemplary embodiment, the magnetic field in the Z direction (along the z-axis) BZ may be controlled by manipulating a duty cycle and/or the amplitude. In an exemplary embodiment, specifically, the duty cycle is the percentage of time a magnet is to receive its rated voltage in a fixed time period. To operate a magnet, it's important to pay attention to the magnet's duty cycle. Most magnets are designed to work at a 50 percent or 75 percent duty cycle. In another embodiment, operation duty cycle is the percentage of total on-time over one complete on and off cycle. The maximum on-time in a cycle is determined by the physical size of an electromagnet. The smaller the electromagnet, the short the maximum on-time. For example, 25% duty cycle with 2 minutes maximum on-time means that every 2 minutes on-time needs 6 minutes off-time. An electromagnet rated continuous duty cycle (100% duty cycle) can run continuously at normal room temperature with convection heat dissipation. An electromagnet rated with intermittent duty cycle (not 100% duty cycle) must run within specified duty cycle in order to avoid overheating the electromagnet. Overheating will lead to premature failure.
[0042] In an exemplary embodiment, at a critical amplitude, there will always be formation of clusters and hence it doesn’t become important in determining the fate of clusters. Whereas, it is the duty cycle that determines how long a cluster remains the same or dissociates. The motility of the cluster can be controlled with the external gradient field and the magnitude of the gradient field. However, the velocities of the particles and/or the clusters may also affected by the size of the particles and/or the cluster and the duty cycle of the magnetic pulse BZ in the Z direction. A larger cluster owing to higher number of particles experiences greater velocity along the gradient compared to a smaller cluster. A cluster with smaller size particles will experience higher velocity than a cluster with larger size particles. Similarly, there exists an interval of duty cycle where the motility increases but after a certain value it begins to decrease. This value indicates that if the magnetic field along the Z axis is switched OFF for a longer time, the cluster might dissociate more than required and hence may result in lower the net velocity.
[0043] Figure 3A illustrates an exemplary embodiment of grouping a collection of particles 320A to form a cluster 330A and disassociating the cluster 330A forming a collection of particles 320A by switching ON and OFF a magnetic field (BZ) along a particular axis (z-axis) (Figure 1A). The strength of the magnetic field may vary depending on the size of the cluster 330A to be formed in the medium 310A, wherein the cluster essentially comprises particulate matter of the substance. In an exemplary embodiment, a gradient magnetic field may be applied along the 2D plane (XY plane) and a pulsating or oscillating magnetic field BZ is applied along the third axis (z-axis) to the medium 310A containing the particles 320A. The dissociation of the cluster is controlled by the duty cycle of the magnetic field BZ in Z direction. A high value of the duty cycle means that the clusters remain intact for a longer time with little time for dissociation of the cluster. On the contrary, if the duty cycle is too low, then the cluster dissociates completely and will end up with a particle distributed in a random manner. Therefore, an optimal value of duty cycle is obtained so as to ensure slight dissociation of the cluster before the cluster may entirely unravel. Because of the inherent property of the collection of particles 320A possessing magnetic properties, application of a magnetic field BZ along the third axis (z-axis) to the medium 310A will organize the particles in a particular orientation causing the particles 320A to form a cluster 330A. It should be obvious to one of ordinary skill in the art, that various other techniques as disclosed previously may be used to form a first cluster 330, and all such techniques of forming the first cluster 320A fall within the scope of the present disclosure.
[0044] When a pulsating or oscillating magnetic field BZ is not applied along a third axis, i.e., the magnetic field BZ is in an OFF state, the cluster 330A will disassociate and form a collection of particles 320A, which may be proximate to each other, Now, when the magnetic field BZ is switched ON, the collection of particles 320A that are proximate to each other will regroup together to form the cluster 330A. Thus, switching OFF the magnetic field BZ along a particular axis, here along the z-axis, tends to disassociate a cluster 330A into a collection of particles 320A in the medium 310A, and switching ON the magnetic field BZ along a particular axis (z-axis) tends to regroup the collection of particles 320A into a cluster 330A. The time period for switching OFF, i.e., the duty cycle, is kept optimal such that the cluster does not completely disassociate, but disassociated sufficiently enough such that the gradient magnetic field along the XY plane make the disassociated cluster, i.e. the particles move in the direction of the gradient and the velocity of the particle moving along the gradient depends on the strength of the magnetic field and the size of the particle. This concept of disassociation of a cluster 330A into a collection of particles 320A and regrouping of the collection of particles 320A into a cluster 330A by using a pulsating magnetic field along a z-axis (BZ) and additionally the medium 310 being provided with a gradient magnetic field along a plane of the other two axes, i.e., the XY plane, can be advantageously used to move a cluster 330A from a first location to a second location as will be discussed in Figure 4.
[0045] Figure 3B illustrates an exemplary schematic view of a collection of particles in the absence of the magnetic field “image A” and the grouping of a collection of particles in the presence of a magnetic field forming a cluster “image B”. In an exemplary view of grouping a collection of particles 320B to form a cluster 330B “image B” by application of a magnetic field (BZ) along a particular axis and disassociating the cluster 330B forming a collection of particles 320B “image A” by switching OFF the magnetic field (BZ) along the z-axis. It should be noted here that the strength of the magnetic field may vary depending on the size of the cluster 330B required. In an exemplary embodiment, a constant magnetic field may be applied along the 2D plane (XY plane) and a pulsating or oscillating magnetic field BZ is applied along the third axis (z-axis) to the medium 310B containing the particles 320B. In an exemplary embodiment, the cluster may include particles of the same size and/or may include particles of differing sizes. However, application of the magnetic field to move the cluster from the first location to the second location may also result in cluster being formed of uniform size over a period of time, which may occur because of the varying velocity of the particle size in the gradient magnetic field.
[0046] As discussed previously, because of the inherent property of the collection of particles 320B possessing magnetic properties, application of a magnetic field BZ along the third axis (z-axis) to the medium 310B will organize or align the particles in a particular orientation causing the particles 320B to form a cluster 330B. In image A, when a pulsating or oscillating magnetic field BZ is not applied along a third axis, i.e., the magnetic field BZ is in an OFF state, the cluster 330B will disassociate forming a collection of particles 320B or the collection of particles 320B will be scattered and randomly distributed when inserted into the medium 310A. In image B, when the magnetic field BZ is switched ON, the particles 320B that are proximate to each other will regroup together to form the cluster 330B or in the scattered distribution the particles of the same sizes proximate to each other group together to form the cluster 330B. Thus, switching OFF the magnetic field BZ along a particular axis, here along the z-axis, tends to disassociate a cluster 330B into a collection of particles 320B in the medium 310B, and switching ON the magnetic field BZ along a particular axis (z-axis) tends to regroup the collection of particles 320B into a cluster 330B.
[0047] Figure 3C illustrates a schematic explaining a simulation model where two colloidal particles lie at the origin and the other at the perimeter of the circle, wherein the simulation shows that there is a net enhancement in the force experienced by the colloids along X and Z directions due to the interactions between the particles, and the simulation further shows that there is a net enhancement in the force experienced by the colloids along X and Z directions due to the interactions between the particles. In the present exemplary case consider the suspension to be inserted into a medium, where the particles are first randomly distributed in the medium. A uniform magnetic field BZ is applied along the z-axis which polarizes the particles and the particles agglomerated to form a cluster structure in the direction of the magnetic field. A gradient magnetic field is present only in two dimension (2D) which is perpendicular to the oscillating or pulsating filed which is responsible for forming the clusters.
[0048] In closely packed suspensions, which are in a colloidal state, the particles possess magnetic properties, and the dipole-dipole interactions between the particles can result in higher net magnetization and hence a higher force than if the particle were isolated in the magnetic field. In an exemplary embodiment, if the dipole-dipole interaction between the particles didn’t exist, the force generated due to a gradient field would be negligible and not enough to induce sufficient velocity for the particles or clusters. In an exemplary embodiment backward and forward propagation of the cluster may be achieved by changing the direction of the gradient magnetic field.
[0049] In an exemplary embodiment, the interaction between the paramagnetic colloids (suspension) in presence of an external magnetic field may be investigated. In an exemplary embodiment, the effect of magnetic gradient field may be amplified due to the interaction of colloids in the cluster. To realize the forces acting on each colloid, it may be essential to probe the net magnetization of a colloid. In an exemplary case considering a paramagnetic colloid, the magnetic moment is directly proportional to the external field, there can be three ways to calculate the net magnetization of the colloidal cluster
a. Fixed dipole model: A simple way is to consider that the magnetization of each colloid is only induced by the external field, and this type of model does not take into account the effect of neighboring colloids and treats each particle as an isolated case.
b. Mutual dipole: This type of model allows for the fields of the other particles to contribute to the magnetization of the bead under consideration.
c. Mutual dipole with multipole effects: wherein multipolar terms are accounted for in the moment calculation, and this only happens when two colloids are separated by a very small distance compared to their radius.
[0050] As mentioned previously, an object of the present disclosure is on the interaction between the colloids and how the interaction between the colloids makes a difference to the motility of the colloids. In an exemplary embodiment, only the first two models are considered and the multipolar effects are ignored. Therefore, in an exemplary embodiment, these models are performed with an assumption that the clusters or colloids are point dipoles. In case of the fixed dipole, the magnetic moment of each colloid and the net force of the cluster are given by
[0051] In the above equations, ‘m’ is the magnetic moment of each colloid in the presence of an external field and ‘F’ is the force on each colloid. The net force experienced by the cluster of colloids in the presence of an external field as the summation of all the forces on each colloid which may be determined from Equation 2 above.
[0052] In an exemplary embodiment, in case of a mutual dipole model, the dipole-dipole interaction between the colloids may be included and the expressions for the moment and force change as follows
[0053] In an exemplary embodiment, each particle ‘n’ has its moment proportional to the external field and the fields due exerted due to the other particles evaluated at the particle ‘n’s center. Consequently, the dipole moment of colloid ‘n’ may be computed using Equation (3). The dipole moments are generally unknown and Equation (3) provides an 3N x 3N linear system of equations needed to determine the dipole moments of each of the cluster in the medium. In an exemplary embodiment, once the dipole moments have been determined from the Equation above, the force on colloid ‘n’ may be computed easily using Equation (4). Which is directly proportional to the velocity of the colloid.
[0054] In an exemplary embodiment, considering a 2D plane (XZ) for two colloids, one each on the center (colloid 1) and the perimeter (colloid 2) of a circle. The Y direction is neglected for sake of simplicity. The force may be calculated on each colloid for different positions of colloid 2 while the colloid 1 is fixed at (0,0). A gradient field of the form B(x)=B0+ Cx may be assumed to be solely present in the X direction. In this exemplary case, the constants B0 = 0.2mT and C = 20mT/m. The forces Fintnet and Fnet may be then calculated as the net force of two colloids with and without interaction respectively. In Figure 3C, the graphs illustrated in (B) and (C) indicate the Fintnet / Fnet as a function of a varying θ (theta). The factor ‘k’ may be used along with the interaction terms to account for the dipole-dipole approximation in the exemplary case. Hence, higher the interacting term, higher is the enhancement of force compared to the a situation that has no-interaction. Therefore, in presence of a gradient field, closely packed colloids experience higher forces than a single colloid and this results in a net velocity of each particle for the closely packed colloid cluster.
[0055] Figure 3D illustrates in (A) and (B) the comparative velocities of a single colloid and cluster when the gradient field is in the X and Y direction respectively. The triangle indicates a single colloidal particle and the circle indicates a cluster. In an exemplary embodiment, a single colloid and cluster of colloids are considered under experimental conditions that may be performed in the laboratory. The gradient field is generated in different directions in the XY plane using for example a Helmholtz coil or any other technique and all such techniques of producing a gradient magnetic field along an XY plane and a pulsating magnetic field along a z-axis are covered within the scope of the present disclosure. The velocity of the single colloid (triangle) is lower than that of the velocity of the cluster (circle) illustrated in Figure 3D. This is attributed to the fact that the interaction between the colloids enhances the effect of gradient magnetic field on the individual particles in the medium. The gradient field may be represented as B(x)=B0+Cx, and based on this, the motility of the cluster may be controlled with the external gradient field and the magnitude of the magnetic field. However, notably the velocities may be affected by the size of the cluster and/or the size of the particles in the cluster and the duty cycle of the magnetic pulse applied in the Z direction. The larger cluster owing to higher number of particles experiences greater velocity compared to a smaller cluster having lesser number of particles in the presence of the magnetic field, and the movement or motility of the cluster is in the direction of the gradient at that point. Similarly, there exists an interval of duty cycle where the motility increases but after a certain value, the motility decreases. This value indicates that if on switching OFF the magnetic field along the Z-axis for a relatively long time, the cluster might dissociate more than required and hence lowers the net velocity.
[0056] In an exemplary embodiment, the gradient magnetic field is present only in two dimensions and is perpendicular to the oscillating field, wherein the oscillating field is responsible for the clustering and de-clustering. In closely packed colloids, wherein the particles possess magnetic properties, the dipole-dipole interactions may result in a higher net magnetization and hence a higher force compared to if the particle was isolated in the magnetic field. If this dipole-dipole interaction didn’t exist, the force generated due to a gradient magnetic field would be negligible and not sufficient to induce a velocity to the particles or the clusters that may make the cluster move. In an exemplary embodiment, change the direction of displacement, i.e., backward moving or forward moving, can be achieved by changing the direction of gradient magnetic field. In an exemplary embodiment, clustering of the particles itself is a stable energy configuration for a highly dense colloidal solution possessing magnetic properties. The action of de-clustering occurs for a relatively small amount of time when the gradient field acts in the absence of the pulsating field (switching OFF the pulsating field) and on switching ON the pulsating field immediately followed by a stable act of clustering.
[0057] Figure 4A illustrates an exemplary schematic of the displacement of a cluster 430 in a medium 410 from a first position (P1) 440 to a second position (P2) 450 by using a pulsating magnetic field BZ along the Z-axis and a gradient magnetic field B along the XY-plane. When a gradient magnetic field B is applied along the 2D plane, i.e., the XY plane, the collection of particles 320 of the suspension in the medium 410 tend to move along the direction of gradient of the magnetic field B at a given point, and the velocity of the particles depending on the gradient of the field and the size of the particles. Figure 4A illustrates an exemplary schematic of the displacement of a cluster 430 from a first position 440 to a second position 450 by using a pulsating magnetic field BZ along the Z-axis and a gradient magnetic field B along the XY-plane, and the movement of the cluster 430 will be in a direction the gradient of the magnetic field in the 2D place at that point, because of the disassociation and regrouping phenomena in the direction of the gradient of the magnetic field B. The movement can be forward or backward depending on the direction of the magnetic field along the XY plane.
[0058] As illustrated in Figure 4A, the pulsating magnetic field BZ is applied in intervals of time, over a time period to cause displacement of the cluster 430 from the first position 440 (Image A) to the second position 450 (Image B). After formation of the cluster 430 using one of the techniques disclosed above, for example applying a constant magnetic field along the z-axis, a gradient magnetic field B is applied along a 2D plane, i.e. the XY plane after the formation of the cluster in the medium. Once the clusters are formed, and the gradient magnetic field is applied along the XY plane, a pulsating magnetic field BZ is applied along the third dimension, i.e., along the z-axis. At a time T0, there is no magnetic field applied along the z-axis, and the collection of particles are disbursed i.e., not in a cluster 430 formation. When the magnetic field is applied along the z-axis, the collection of particles that are proximate to each other group together to form a cluster 430. Each cluster 430 has its own center of mass, wherein the center of mass of the cluster 430 will be the center of mass of the collection of particles forming the cluster 430. When the magnetic field BZ is applied the center of mass for the cluster 430 at the first location 440 is at a point P1. Now when the magnetic field is switched OFF at time T2, the cluster disassociated into a collection of particles which may be dispersed proximate to each other and the particles move in a direction of the gradient filed along the XY plane, depending on the strength of the magnetic field and the size of the particles. When the magnetic field BZ is applied again at time T3, the particles 420 that are proximate to each other and will regroup to form the cluster at a second position 450 now at P2, which is displaced from the first location P1 because of the movement of the collection of particles along the gradient of the filed along the XY plane, and the center of mass of the cluster 430 will move from the position P1 at 440 to the new center of mass position P2 at 450. In an exemplary case, if there are particles of differing sizes, the on disassociation and movement along the gradient field direction, smaller particles may move faster compared to larger particles and hence on application of the [pulsating field after a time, t=particles of the same size that have moved a distance may regroup to form a cluster and particles of a different size may form another cluster, thereby a single initial cluster could be split into multiple different clusters depending on the size of the particles. The cycle of switching OFF and switching ON the magnetic field in manner over time until the cluster 430 reaches the intended targeted location P3 460 from the first location 440.
[0059] Figure 4B illustrates particle formed in a cluster with a receptor. Depending on the size of the particle and the receptor attached to the particle can be displaced from a first position to a second position. In an exemplary embodiment, depending on the chemical properties and physical properties of the receptor (452) bound to the particles (450), such as charge, size, presence of hydrogen bonds etc., the size of the cluster may vary and hence these may have a different velocity of movement along the gradient magnetic field. In an exemplary embodiment, a smaller receptor 454 attached to the particle 450 make the particle size smaller and hence move faster along the gradient magnetic field. These receptors 452, 454 may be sensors attached to the particles to perform a certain known function. In an exemplary case, the receptor could be a chemical moiety, such as a protein or a DNA or as aptamer or an antibody or an radioactive substance with specific conjugation properties with another chemical moiety possibly present within the suspension. The receptor may be magnetic or non-magnetic but will modify the physical and chemical properties of each particle in the cluster. The properties of a particle and cluster may be functionally controlled by adding the receptor 452, 454 to the particle. Again, as discussed previously, larger the size of the cluster, lower the velocity along the gradient magnetic field and smaller the size of the particle higher the velocity along the gradient magnetic field. In an exemplary case the receptor may be a sensor to detect the presence of a certain chemical or biochemical moiety present within the suspension. In an exemplary embodiment, attaching a radioactive receptor to the particle may be advantageous to cluster the particle together and treat a specific area such as the liver. In another exemplary embodiment, the radioactive receptor may be configured to be a sensor wherein after the particle’s are clustered, the radioactive properties of the particles may be used to gain information and/or data about the cells and/or the reaction of the particles and/or any anomalies in a targeted area.
[0060] Figure 5A illustrates an exemplary method of preparing a suspension or a colloidal state of a substance. In step 510, a substance is taken and mixed with a measured quantity of a fluid to create a suspension of the substance. The suspension (also referred to as a colloidal state or colloidal suspension) of the substance in the fluid essentially contains a collection of particles of the substance in the fluid. The size of the particles may vary in a range of 1 milli meter to about 1 nano meter. The fluid used to create the suspension of the substance may be one of a Newtonian fluid or a non-Newtonian fluid. In step 520, the suspension is inserted into a medium. On insertion into the medium, the suspension disperses in the medium and is dispersed in a local region. Normally, the suspension is inserted into the medium at a location proximate to the intended targeted location. The point of insertion of the suspension may be considered to be the first point in the medium, and the targeted location may be considered to the second point, where the suspension is intended to be delivered from the first location to the target location.
[0061] Figure 5B illustrates an exemplary method of forming a cluster in the medium after the suspension has been inserted into the medium. The suspension, which consists of a collection of particles possesses magnetic properties. Once inserted into the medium the suspension is normally dispersed in a localized region in a random manner. In step 530, a cluster or a group of clusters, which consists of a collection of particles is formed. In one embodiment, in step 535 a magnetic field is applied along the z-axis to the collection of particles in a medium, which orients the particles in a particular manner and also groups the particles proximate to each other forming either a single cluster or a group of clusters. Forming the cluster is an important aspect associated with the transportation of the cluster, collection of particles, form a first location to a second location.
[0062] Figure 5C illustrates an exemplary method of delivering the cluster to a targeted location in accordance with the present disclosure. As disclosed previously, after inserting the suspension into the medium, first a cluster is formed. In step 540, the target location for delivery of the suspension is identified, the suspension is normally inserted proximate to the target location and dispersed locally, after which the cluster formation happens. After forming a cluster or a group of clusters of the suspension in the medium, a gradient magnetic field is applied along a plane, i.e., in the XY plane. After applying the gradient magnetic field in the XY plane, in step 560 a pulsating magnetic field is applied along the third axis not in the 2D (XY) place, i.e., along the z-axis.
[0063] In step 580, the gradient magnetic field may be kept constant, wherein the cluster in the medium is present. The cluster formed has a center of mass as described previously. In step 580, the magnetic field along the z-axis is switched off, in which case the cluster disassociated to a collection of particles, and the particles move in the direction of the gradient at that point. Now the magnetic field is switched ON along the z-axis. When the magnetic field is switched ON, the collection of particles forms the cluster again, however the center of mass of the cluster would have shifted from a first position P1 to a second position P2 (as described previously). Since the center of mass of the cluster has shifted, the collection of particles forming the cluster has moved from a first location P1 to a second location P2. Cyclically repeating the step of 580, of switching OFF and switching ON the magnetic field along the z-axis, the center of mass of the cluster is shifted and the cluster is displaced from a first location to a second location, until the cluster reaches the intended targeted location P3.
[0064] In an exemplary case, to treat fatty liver disease, first a substance/compound to treat such a disease is identified. Lipid lowering drugs such as statins or ezetimibe may be identified to treat a fatty liver. These are water soluble drugs and the drug is first dissolved in a fixed or measured quantity of water and a suspension is formed. The suspension has a collection of the drug particles in it, which may be in a colloidal state, and the size of the drug particles may have a diameter that will be in the range of a few nano meters. Once the suspension is prepared, the suspension may be injected into the medium such as blood (a non-Newtonian fluid), and the suspension will be locally dispersed in a certain region around the point of insertion. The patient may be kept in a 3D magnetic field, wherein a gradient magnetic field is applied along the XY plane and a pulsating magnetic field is applied along the z-axis. The target location of the delivery of the drug in the object (human) is the liver. First a cluster of the suspension is formed at the point of insertion into the object (human). Now the gradient filed and the pulsating filed can work in conjunction to disassociate the cluster and regroup the collection of particles of the drug into a cluster, such that the cluster may be delivered to an intended location of the object, i.e., the liver of the object. This method of drug delivery may have greater impact as the entire drug may be delivered to the correctly identified location, thereby causing the object to react faster to the treatment.
[0065] Further, in the field of nano technology, there has been a lot of attention on micro and nanorobots swimming in complex media and performing tasks related to transport and therapeutics. The motility of such nanoscale objects may be performed using energy sources like electric, chemical, magnetic, light and enzymes to energize the system. These nanoscale objects need to be compatible with the medium, for example a human or animal, and should not result in altering any of their physical or chemical properties, or in a viscous medium having a low Reynold number associated with the medium, such as blood or saliva or any other bodily fluids. Therefore, in accordance with the present disclosure, driving these miniature robots using magnetic fields addresses most of the problems that have been noticed and this technique of using magnetic fields has proven to be biocompatible. Additionally, the energy associated with the nanoscale objects is due to a physical field, and that makes them medium-independent. Therefore, in accordance with the present disclosure using small magnetic gradients net motility of colloids at nanoscale may be achieved. These particles can be easily assembled and disassembled along with navigating them around small porous spaces or obstacles using the magnetic fields as described in the present disclosure.
[0066] Although the operations of the method according to the embodiments of the present disclosure are described in a specific order in the drawings, it does not require or imply that these operations have to be performed in that specific order, or a desired result can only be achieved by performing all of the illustrated operations. On the contrary, the steps illustrated in the flow diagrams may change their execution order. Additionally, or alternatively, some steps may be omitted, a plurality of steps may be combined into one step for execution, and/or one step may be decomposed into a plurality of steps for execution. It should also be noted that the features and functions of two or more modules according to the embodiments of the present disclosure may be embodied in one module. In turn, features and functions of one module described above may also be further divided into a plurality of modules for embodiment.
[0067] Although the present disclosure has been described with reference to several preferred embodiments, it should be understood that the present disclosure is not limited to the preferred embodiments disclosed here. Embodiments of the present disclosure intend to cover various modifications and equivalent arrangements within the spirit and scope of the appended claims. Although the foregoing disclosure has been described in some detail for purposes of clarity of understanding, it will be apparent that certain changes and modifications may be practiced within the scope of the appended claims. Examples of the present disclosure have been described in language specific to structural features and/or methods. It should be noted that there are many alternative ways of implementing both the process and apparatus of the present invention. Accordingly, the present embodiments are to be considered illustrative and not restrictive, and the invention is not to be limited to the details given herein but may be modified within the scope and equivalents of the appended claims. It should be understood that the appended claims are not necessarily limited to the specific features or methods described. Rather, the specific features and methods are disclosed and explained as examples of the present disclosure.
, Claims:1. A method for motility of a cluster from a first position to a target position, the method comprising:
- forming a suspension of a substance by mixing the substance in a fluid, wherein the suspension comprises a collection of particles 120, wherein the collection of particles in the suspension possesses magnetic properties;
- inserting the suspension into a medium 110;
- forming a first cluster 230 comprising the collection of particles;
- in a three-dimensional space of the first cluster 230, providing a gradient magnetic field along a two-dimensional (2D) (XY) plane and a pulsating magnetic field along a third axis (z-axis), wherein the gradient magnetic field along the 2D plane in conjunction with the pulsating magnetic field along the third-axis displaces the cluster 130 from a first position to a second position.
2. The method as claimed in claims 1, wherein a diameter of the cluster 230 is dependent on the particle density and the strength of the magnetic field.
3. The method as claimed in claim 1, wherein a velocity of the particle along the gradient magnetic field is proportional to the strength of the magnetic field and inversely related to the viscous friction of the fluid suspension.
4. The method as claimed in claim 1, wherein the velocity of the particle along the gradient magnetic field is proportional to the size of the particle, wherein a particle of smaller dimension moves with a higher velocity in the direction of the gradient magnetic field than a particle of larger size.
5. The method as claimed in claim 1, wherein the medium 210 for transportation of the cluster 230 comprises at least one of a Newtonian fluid or a non-Newtonian fluid.
6. The method as claimed in claim 5, wherein the medium 210 comprises at least one of a liquid or a semi-solid or a gel.
7. The method as claimed in claim 1, wherein forming the first cluster 230 in the medium 210 comprises:
- controlling at least one of a pH of the suspension and/or a temperature of the suspension and/or a temperature of the medium 210 and/or applying a constant magnetic field to the medium 210 for a predetermined time.
8. The method as claimed in claim 1, comprises:
- disassociating the cluster 330B by switching OFF the magnetic field along the third-axis for a first time period.
9. The method as claimed in claim 8, comprises:
- applying a gradient magnetic field in a 2D place, wherein the direction of motility of the disassociated collection of particles 320A is dependent on the gradient of the magnetic field in the 2D plane at that point.
10. The method as claimed in claim 9, comprises
- switching ON the magnetic field along the third axis after first time period for a second time period, wherein the collection of particles 320A regroup to form the cluster 330B.
11. The method as claimed in claims 7 -10, wherein a center of mass associated with the cluster 430 is displaced from a first position 440 to a second position 450.
12. The method as claimed in claim 9, wherein the direction and magnitude of displacement of the center of mass of the cluster 430 is dependent on the gradient of the magnetic field in the 2D plane at that point.
13. The method as claimed in claim 1, wherein the suspension includes a receptor that binds specifically to the particle modifying the effective size of the cluster.
14. The method as claimed in claim 1, wherein a target molecule may be attached to each of the collection of particles of the suspension changing inter-particle physical interactions and chemical interactions, and thereby changing the effective size of the cluster, wherein clustering dynamics and/or speed of the cluster under the magnetic actuation will be modified.
15. The method as claimed in claim 13, wherein the receptor is a chemical moiety with specific conjugation properties with the suspension having another chemical moiety.
16. The method as claimed in claim 14, wherein efficiency of the cluster remains intact when a duty cycle of the magnetic field along the z-axis is high.
17. The method as claimed in claim 14, wherein the cluster remains disassociates when a duty cycle of the magnetic field along the z-axis is low.
18. The method as claimed in claim 14, wherein the velocity of motility of the cluster with the target molecule is low as the size of the cluster increases.
19. A method for delivering an object to a targeted location, the method comprising:
- identifying a targeted delivery location of delivery an object;
- forming a suspension of the object, wherein the suspension comprises mixing the object in a fluid and the suspension a collection of particles possessing magnetic properties;
- inserting the suspension proximate to the target location in a medium, wherein the medium comprises either one of a Newtonian fluid or a non-Newtonian fluid;
- forming a first cluster in the medium; and
- in a three-dimensional (3D) space of the cluster 430, providing a gradient magnetic field along a two-dimensional (XY) plane and a pulsating magnetic field along a third axis (z-axis), wherein the gradient magnetic field along the 2D place plane in conjunction with the pulsating magnetic field along the third-axis displaces the cluster 430 from a first position 440 to a second position 450.
20. The method as claimed in claim 19, comprising:
- disassociating the cluster by switching OFF the magnetic field along the third axis for a first time period (T0), wherein a direction of disassociation of the cluster is dependent of the gradient of the magnetic field at that point in the 2D plane.
- regrouping the collection of particles to form the cluster by switching ON the magnetic field along the third axis for a second time period (T1).
21. The method as claimed in claim 20, wherein a center of mass associated with the cluster is displaced from the first position (P1, 440) to the second position (P2,450) in a direction of the gradient magnetic field at that point in the 2D plane when the magnetic field along the third axis is switched OFF and switched ON in periodic intervals.
22. The method as claimed in claims 20, comprises
- repeating cyclically switching OFF and switching ON the magnetic field along the third axis until the cluster is displaced from a first location (P1,440) to a target location (P3,460).
23. The method as claimed in claim 19, wherein the suspension includes a receptor that binds specifically to the particle modifying the effective size of the cluster.
24. The method as claimed in claim 23, wherein a target molecule may be attached to each of the collection of particles of the suspension changing inter-particle physical interactions and chemical interactions, and thereby changing the effective size of the cluster, wherein clustering dynamics and/or speed of the cluster under the magnetic actuation will be modified.
25. The method as claimed in claim 33, wherein the receptor is a chemical moiety with specific conjugation properties with the suspension having another chemical moiety.
26. The method as claimed in claim 23, wherein the receptor is a radioactive particle targeted to be delivered to a specific area of an object.
27. A system configured to perform the method as claimed in the any of the preceding claims 1 to 18.
28. A system configured to perform the method as claimed in any of the preceding claims 19 to 26.
| # | Name | Date |
|---|---|---|
| 1 | 202341030146-STATEMENT OF UNDERTAKING (FORM 3) [26-04-2023(online)].pdf | 2023-04-26 |
| 2 | 202341030146-REQUEST FOR EARLY PUBLICATION(FORM-9) [26-04-2023(online)].pdf | 2023-04-26 |
| 3 | 202341030146-POWER OF AUTHORITY [26-04-2023(online)].pdf | 2023-04-26 |
| 4 | 202341030146-FORM-9 [26-04-2023(online)].pdf | 2023-04-26 |
| 5 | 202341030146-FORM FOR SMALL ENTITY(FORM-28) [26-04-2023(online)].pdf | 2023-04-26 |
| 6 | 202341030146-FORM 1 [26-04-2023(online)].pdf | 2023-04-26 |
| 7 | 202341030146-EVIDENCE FOR REGISTRATION UNDER SSI(FORM-28) [26-04-2023(online)].pdf | 2023-04-26 |
| 8 | 202341030146-EVIDENCE FOR REGISTRATION UNDER SSI [26-04-2023(online)].pdf | 2023-04-26 |
| 9 | 202341030146-EDUCATIONAL INSTITUTION(S) [26-04-2023(online)].pdf | 2023-04-26 |
| 10 | 202341030146-DRAWINGS [26-04-2023(online)].pdf | 2023-04-26 |
| 11 | 202341030146-DECLARATION OF INVENTORSHIP (FORM 5) [26-04-2023(online)].pdf | 2023-04-26 |
| 12 | 202341030146-COMPLETE SPECIFICATION [26-04-2023(online)].pdf | 2023-04-26 |
| 13 | 202341030146-FORM 18A [27-04-2023(online)].pdf | 2023-04-27 |
| 14 | 202341030146-EVIDENCE OF ELIGIBILTY RULE 24C1f [27-04-2023(online)].pdf | 2023-04-27 |
| 15 | 202341030146-ENDORSEMENT BY INVENTORS [17-05-2023(online)].pdf | 2023-05-17 |
| 16 | 202341030146-FER.pdf | 2023-07-17 |
| 17 | 202341030146-FORM-26 [17-01-2024(online)].pdf | 2024-01-17 |
| 18 | 202341030146-FER_SER_REPLY [17-01-2024(online)].pdf | 2024-01-17 |
| 19 | 202341030146-DRAWING [17-01-2024(online)].pdf | 2024-01-17 |
| 20 | 202341030146-CORRESPONDENCE [17-01-2024(online)].pdf | 2024-01-17 |
| 21 | 202341030146-COMPLETE SPECIFICATION [17-01-2024(online)].pdf | 2024-01-17 |
| 22 | 202341030146-CLAIMS [17-01-2024(online)].pdf | 2024-01-17 |
| 23 | 202341030146-ABSTRACT [17-01-2024(online)].pdf | 2024-01-17 |
| 24 | 202341030146-RELEVANT DOCUMENTS [31-01-2024(online)].pdf | 2024-01-31 |
| 25 | 202341030146-FORM 13 [31-01-2024(online)].pdf | 2024-01-31 |
| 26 | 202341030146-FORM-8 [01-02-2024(online)].pdf | 2024-02-01 |
| 27 | 202341030146-US(14)-HearingNotice-(HearingDate-06-03-2024).pdf | 2024-02-13 |
| 28 | 202341030146-Correspondence to notify the Controller [01-03-2024(online)].pdf | 2024-03-01 |
| 29 | 202341030146-FORM-26 [04-03-2024(online)].pdf | 2024-03-04 |
| 30 | 202341030146-Written submissions and relevant documents [21-03-2024(online)].pdf | 2024-03-21 |
| 31 | 202341030146-PETITION UNDER RULE 137 [21-03-2024(online)].pdf | 2024-03-21 |
| 32 | 202341030146-Annexure [21-03-2024(online)].pdf | 2024-03-21 |
| 33 | 202341030146-PatentCertificate08-04-2024.pdf | 2024-04-08 |
| 34 | 202341030146-IntimationOfGrant08-04-2024.pdf | 2024-04-08 |
| 1 | SearchHistory(10)E_11-07-2023.pdf |