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Title:
SYNTHETIC MAGNETIC STRUCTURES AND THE MANUFACTURE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/240564
Kind Code:
A1
Abstract:
A synthetic magnetic monopole comprises a magnetization layer having two magnetization directions in a plane perpendicular to a substrate. The magnetization layer is aligned in either of the two magnetization directions, either into or out of the substrate, such that one magnetic pole is exposed and one magnetic pole is absorbed or hidden in the substrate, thereby to provide a synthetic magnetic monopole. The particle may be at the micron scale with the magnetization particles or layer at the nano-scale and the synthetic magnetic monopoles may be useful for investigating chirality in other molecules.

Inventors:
CAPUA EYAL (IL)
Application Number:
PCT/IL2020/050597
Publication Date:
December 03, 2020
Filing Date:
May 27, 2020
Export Citation:
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Assignee:
KIRALIS TECH LTD (IL)
International Classes:
B03C1/033; B03C1/00; G01N30/00
Domestic Patent References:
WO2019043693A12019-03-07
Foreign References:
US20060130192A12006-06-15
Other References:
CHESNEL, K: "Nanoscale Magnetic Domain Memory", INTECHOPEN, 20 December 2017 (2017-12-20), XP081718993, Retrieved from the Internet [retrieved on 20200820], DOI: 10.5772/intechopen.71076
JAMALI, M ET AL.: "Sputtering of cobalt film with perpendicular magnetic anisotropy on disorder-free graphene", AIP ADVANCES, vol. 4, no. 10, 15 October 2014 (2014-10-15), XP012190419, Retrieved from the Internet [retrieved on 20200820], DOI: 10.1063/1.4897333
BANERJEE-GHOSH, K ET AL.: "Separation of enantiomers by their enantiospecific interaction with achiral magnetic substrates", SCIENCE, vol. 360, no. 6395, 22 June 2018 (2018-06-22), pages 1331 - 1334, XP055647572, Retrieved from the Internet [retrieved on 20200820], DOI: 10.1126/science.aar4265
Attorney, Agent or Firm:
EHRLICH, Gal et al. (IL)
Download PDF:
Claims:
WHAT IS CLAIMED IS:

1. A synthetic magnetic structure comprising a magnetic layer having a first magnetization direction and a second magnetization direction, and a substrate, the first and second magnetization directions being perpendicular to, and towards and away from, a surface of said substrate, and the first and second magnetization directions being aligned such that one magnetic pole is exposed and one magnetic pole is hidden within said substrate, thereby to provide a synthetic magnetic monopole.

2. The synthetic magnetic structure of claim 1, wherein said magnetic layer comprises magnetic materials, said materials comprising at least one member of the group consisting of Fe, Ni, Co, Gd and Cr.

3. The synthetic magnetic structure of claim 1 or claim 2, wherein said magnetic layer comprises one member of the group consisting of BaFe, superparamagnetic FeO, and a deposited layer having perpendicular magnetic anisotropic (PMA) characteristics.

4. The synthetic magnetic structure of claim 1, wherein the substrate comprises a microbead, the magnetization layer being coated onto the microbead.

5. The synthetic magnetic structure of claim 4, wherein the microbead has a diameter ranging between 1 and 1000 microns or between 2 and 25 microns.

6. The synthetic magnetic structure of claim 1, wherein the magnetization layers comprise nanoscale magnetization domains.

7. The use of a synthetic magnetic structure according to any one of claims 1, 2 or 4 to 6, to measure chirality in other molecules.

8. A method of manufacturing a synthetic magnetic monopole comprising:

obtaining a substrate;

coating a first surface of the substrate with a magnetizing layer; and aligning magnetizations within the magnetizing layer such that all magnetizations are aligned in a single magnetization direction, said single magnetization direction being perpendicular to said coated first surface of said substrate.

9. A method of manufacturing a synthetic magnetic monopole comprising:

obtaining magnetic nanoparticles;

arranging the magnetic nanoparticles on a surface;

magnetizing the nanoparticles into a single direction;

carrying out a chemical modification to one side of said aligned nanoparticles; and releasing said particles in the presence of microbeads, to allow said chemical modification to capture said nanoparticles and align said nanoparticles in a single magnetization alignment on said microbeads, the single magnetization alignment being perpendicular to a surface of said microbead.

10. A method of manufacturing a synthetic magnetic nanoparticle comprising:

obtaining a microbead;

coating said microbead with a layer of magnetizing nanoparticles; and

applying a magnetic write head to align said magnetizing nanoparticles in a single magnetization alignment, the single magnetization alignment being perpendicular to a surface of said microbead.

1 1. The method of claim 9, wherein said arranging or coating the magnetic nanoparticles comprises chemical adsorption onto said bead or substrate.

12. The method of claim 11, wherein said chemical adsorption comprises binding the layer of magnetic nanoparticles to the bead or substrate using a binding chemistry.

13. The method of claim 12, wherein said binding using a binding chemistry comprises using one member of the group of chemical binding methods consisting of: polymeric acrylic binding, epoxy-based, amino-based, carboxy-based, thiol-based, and biotin based binding.

14. The method of claim 11, wherein said chemical adsorption comprises using a chiral molecule.

15. The method of claim 8 or claim 10, wherein said aligning said magnetizing nanoparticles comprises:

placing said coated microbeads in a container; and

applying a write head to said microbeads while rotating said microbeads.

16. The method of claim 8, wherein said magnetizing of the magnetization layer comprises applying an external magnetic field while blocking an undesired pole using a passivation layer, thereby to appear as a monopole to respective surroundings.

17. The method of claim 16, wherein said passivation layer comprises a non-magnetic layer.

18. The method of claim 8, wherein said arranging or coating the magnetic nanoparticles comprises physical deposition.

19. The method of claim 18, wherein said physical deposition comprises sputtering, or evaporation.

20. The method of claim 8 or claim 9, wherein said arranging or coating the magnetic nanoparticles comprises direct synthesis on the substrate.

21. The method of claim 8, wherein said arranging or coating the magnetic nanoparticles comprises chemical adsorption via a chiral molecule.

Description:
SYNTHETIC MAGNETIC STRUCTURES AND

THE MANUFACTURE THEREOF

RELATED APPLICATION/S

This application claims priority of US Provisional Patent Application No. 62/854,330 Filed May 30, 2019, the contents of which are hereby incorporated herein by reference in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to a synthetic magnetic structure and ways of manufacturing the same and, more particularly, but not exclusively, to a magnetic structure where only a single pole is exposed to the environment.

Magnetic monopoles are known today only in theory and no clear evidence of their existence has yet been found.

Some kind of magnetic monopole would be useful for the exploitation of magnetic characteristics of chiral molecules to separate two enantiomers or other such molecules with specific magnetic spins.

Molecular chirality is a geometrical property found in many natural materials and molecules, such as in nucleic acids, amino acids, sugars and more. This property was discovered already about 200 years ago by Jean Baptiste Biot and Louis Pasteur, yet the realization of its chemical and pharmaceutical importance was mostly claimed only after the unfortunate thalidomide tragedy.

Today, molecular chirality plays a major role in the production of novel drugs, pesticides, herbicides, fragrances and even flavors. The production and monitoring of chiral compounds at high resolution is important and much effort is being applied to obtain the necessary capabilities. The chiral purity, or enantiomeric excess, of racemic mixtures are studied and monitored using various analytical methods that are based variously on optical rotation, circular dichroism, NMR, and chiral chromatography. With respect to separation of chiral compounds, various methods exist yet they rely solely on the geometrical differences between different isomers of the same chiral molecule. Among these are crystallization of conglomerates, chemical derivation via diasteriomers, and chiral chromatography. These methods are considered as cumbersome and costly and in many cases are of limited efficiency.

In some recent academic findings, led by Prof. Naaman and his colleagues, it was realized that electronic spins are generated in chiral molecules upon charge re-arrangement within the molecules. This phenomenon was realized over numerous molecular systems and was termed the chiral induced spin selectivity (CISS) effect. This was further elaborated to more applicable purposes in which the CISS effect was said to be utilized in order to separate mirrored isomers within racemic mixtures based on the magnetic interactions between chiral molecules and magnetic surfaces.

As mentioned above, some kind of magnetic monopole would be useful for the exploitation of magnetic characteristics of chiral molecules to separate two enantiomers or other such molecules with specific magnetic spins. There are however no techniques in the current art to manufacture synthetic magnetic monopoles. SUMMARY OF THE INVENTION

The present invention relates to one or more manufacturing processes in which synthetic magnetic monopoles are produced; namely, processes and the resulting structures in which only one pole is exposed to the surroundings while the other pole is hidden or protected. The present embodiments thus relate to the manufacturing of the magnetic elements, the magnetization of these particles and their testing to verify their vertical magnetic spin alignment.

The present embodiments may thus supply a means for improved efficiency of magnetic and spin-based molecular interactions by increasing surface areas containing only one specific spin. Such embodiments may thus be used both in analytical systems (as in chromatography columns) and in synthesis and production of compounds and materials.

The present embodiments may further provide benefits in applications in the fields of magnetics and spintronics, such as in magnetic memory, mechanical manipulations, labeling, magnetic resonance imaging, vibrational energy harvesting, etc.

According to an aspect of some embodiments of the present invention there is provided a synthetic magnetic structure comprising a magnetic layer having a first magnetization direction and a second magnetization direction, and a substrate, the first and second magnetization directions being perpendicular to, and towards and away from, a surface of the substrate, and the first and second magnetization directions being aligned such that one magnetic pole is exposed and one magnetic pole is hidden within the substrate, thereby to provide a synthetic magnetic monopole.

In an embodiment, the magnetic layer comprises magnetic materials, the materials comprising at least one member of the group consisting of Fe, Ni, Co, Gd and Cr.

In an embodiment, the magnetic layer compri ses one member of the group consisting of BaFe, superparamagnetic FeO, and a deposited layer having perpendicular magnetic anisotropic (PMA) characteristics. In an embodiment, the substrate comprises a microbead, the magnetization layer being coated onto the microbead.

In an embodiment, the microbead has a diameter ranging between 1 and 1000 microns or between 2 and 25 microns.

In an embodiment, the magnetization layers comprise nanoscale magnetization domains. An embodiment comprises the use of any of the synthetic magnetic structures discussed herein, to measure chirality in other molecules.

According to a second aspect of the present invention there is provided a method of manufacturing a synthetic magnetic monopole comprising:

obtaining a substrate;

coating a first surface of the substrate with a magnetizing layer; and

aligning magnetizations within the magnetizing layer such that all magnetizations are aligned in a single magnetization direction, the single magnetization direction being perpendicular to the coated first surface of the substrate.

According to a third aspect of the present invention there is provided a method of manufacturing a synthetic magnetic monopole comprising:

obtaining magnetic nanoparticles;

arranging the magnetic nanoparticles on a surface;

magnetizing the nanoparticles into a single direction;

carrying out a chemical modification to one side of the aligned nanoparticles; and releasing the particles in the presence of microbeads, to allow the chemical modification to capture the nanoparticles and align the nanoparticles in a single magnetization alignment on the microbeads, the single magnetization alignment being perpendicular to a surface of the microbead.

According to a fourth aspect of the present invention there is provided a method of manufacturing a synthetic magnetic nanoparticle comprising:

obtaining a microbead;

coating the microbead with a layer of magnetizing nanoparticles; and

applying a magnetic write head to align the magnetizing nanoparticles in a single magnetization alignment, the single magnetization alignment being perpendicular to a surface of the microbead.

In variations of the method, arranging or coating the magnetic nanoparticles comprises chemical adsorption onto the bead or substrate.

In variations of the method, chemical adsorption comprises binding the layer of magnetic nanoparticles to the bead or substrate using a binding chemistry. In an embodiment, the binding using a binding chemistry comprises using one member of the group of chemical binding methods consisting of: polymeric acrylic binding, epoxy-based, amino-based, carboxy-based, thiol-based, and biotin based binding.

In an embodiment, chemical adsorption comprises using a chiral molecule.

In an embodiment, the aligning the magnetizing nanoparticles comprises:

placing the coated microbeads in a container; and

applying a write head to the microbeads while rotating the microbeads.

In an embodiment, the magnetizing of the magnetization layer comprises applying an external magnetic field while blocking an undesired pole using a passivation layer, thereby to appear as a monopole to respective surroundings.

In an embodiment, the passivation layer comprises a non-magnetic layer.

In an embodiment, arranging or coating the magnetic nanoparticles comprises physical deposition.

In an embodiment, the physical deposition comprises sputtering, or evaporation.

In an embodiment, the arranging or coating the magnetic nanoparticles comprises direct synthesis on the substrate.

In an embodiment, the arranging or coating the magnetic nanoparticles comprises chemical adsorption via a chiral molecule.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced. In the drawings:

FIG. 1A is a schematic drawing of a magnetized particle according to the present embodiments;

FIG. IB shows a schematic drawing of a microsphere made into a monopole according to the present embodiments;

FIG. 2 is a simplified flow chart showing direct synthesis of BaFe onto silica;

FIGs 3A to 3C are three electron micrographs showing microspheres coated with barium ferrite at different scales according to embodiments of the present invention;

FIG. 4 is a simplified diagram illustrating magnetization on a microsphere according to embodiments of the present invention;

FIG. 5 A is a graph of the magnetic hysteresis of barium ferrite;

FIG. 5B is a variation of the graph of Fig. 5 A as achieved during the production process; FIG. 6 A is a simplified schematic diagram that illustrates the use of a magnetic drive for perpendicular magnetic recording to magnetize microspheres according to the present embodiments;

FIG. 6B is a schematic diagram illustrating a prototype of the drive of FIG. 6A built according to an embodiment of the present invention;

FIG. 7 is a simplified flow chart showing a method of making synthetic magnetic monopoles by modifying a BaFe single pole chemically and bind to a micro-bead surface according to embodiments of the present invention;

FIG. 8 is a schematic diagram illustrating a series of exemplary chemistries for adsorption of BaFe;

FIG. 9A is a simplified flow chart illustrating a method of making magnetic particles by alignment on a flat substrate and binding back-to-back to form micro-quadrupoles, according to embodiments of the present invention;

FIG. 9B is a simplified schematic diagram of a particle made according to the method of

Fig. 9 A;

FIG. 10 is a simplified diagram illustrating a method of manufacturing a magnetic particle according to the present embodiments using a pre-lithographed wafer;

FIG 11 is a simplified diagram showing particles aligning with a microsphere using the chiral induced spin selectivity effect (CISS); and

FIG. 12 is a simplified schematic diagram showing a microbead with a dipolar structure and where a passivation layer is used on one of the orientations, according to an embodiment of the present invention. DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to a synthetic magnetic structure and ways of manufacturing the same and, more particularly, but not exclusively, to a magnetic structure where only a single pole is exposed to the environment.

A synthetic magnetic structure or synthetic magnetic monopole according to the present embodiments comprises a particle coated with a magnetic layer having two magnetization directions in a plane perpendicular to a substrate, for example perpendicular magnetic anisotropic surfaces; PMAs. The magnetization particles are all identically aligned in either of the two magnetization directions, either into or out of the substrate, such that one magnetic pole is exposed and one magnetic pole is absorbed or hidden in the substrate, thereby to provide a synthetic magnetic monopole. The particle may be at the micron scale with the magnetization layer at the nano-scale and the synthetic magnetic monopoles may be useful for investigating chirality in other molecules.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the detail s of construction and the arrangement of the components and/or methods set forth in the following description and/or illustrated in the drawings and/or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. A series of exemplary embodiments for producing artificial monopoles are summarized in table 1 and discussed below.

Referring now to the drawings, Figure 1 A illustrates a monopolar core-shell micro-bead 10 according to a first embodiment of the present invention.

The core 12 is a bead in the micro-size order of magnitude (1 -1000 um) and is coated with a magnetic shell layer 14. The shell may be formed in stages in a number of embodiments of which a number are exemplified below.

Fig. IB shows a monopolar core-shell microbead comprising a silica bead in the microscale, microsphere 34, with a magnetic layer 36 polarized in accordance with arrows 38 out of plane, that is outwardly of the microsphere.

One set of methods for producing an artificial magnetic monopole according to the present embodiments is to directly synthesize barium ferrite on silica and then magnetize using perpendicular magnetic recording devices.

Figure 2 is a simplified flow chart that illustrates a variation in which direct synthesis of Ba-ferrite on the surfaces of the micro-beads is carried out 30.

Figures 3 A - 3C are electron micrographs showing constructions made according to Fig. 2, and Fig 4 schematically illustrates the magnetization, as will be discussed below. In brief, the synthesis process may be carried by crystallization of a sol-gel intermediate containing a mixture ofBa(NO 3 ) 2 and Fe(NO 3 ) 3 at a ratio of 1:18, respectively, and in the presence of silica beads. The crystallization may occur at a temperature of about 1000 °C for about 2 hours in order to form the appropriate crystallographic and magnetic phase. The magnetic beads are then magnetized by presenting to an ultra-fine monopolar magnetic head that exploits proper vertical magnetic fields -

32.

Reference is now made to Figs 3A to 3C which are three electron micrographs at successively increasing magnifications, of micro-beads coated with barium ferrite as obtained from the direct synthesis approach. Energy dispersive X-ray spectroscopy (EDX) analysis was used to confirm that the spheres manufactured were indeed barium ferrite.

Reference is now made to Fig. 4 which illustrates a process of magnetizing the coated beads. The beads 70 are initially coated with Barium ferrite nanoparticles 72 that are magnetized variously into and out of the beads. Coating may use any method, including those mentioned above and may be based on direct synthesis or selective chemistry. Then magnetization 74 is used to align the magnetizations so that all point out of the bead 76.

In this connection, Fig 5A is a graph showing magnetic moment against field for barium ferrite. Fig. 5B is a graph showing the actual hysteresis achieved in the production process.

Reference is now made to Fig. 6 A, which is a simplified diagram showing how a multi perpendicular magnetic recording (PMR) head may be used to align the magnetizations of the bead. A beaker 110 is filled with Barium-ferrite coated beads. The writing head 112 is at the end of a flex wire towards the interior of the beaker 1 10. The beaker rotates allowing the writing head to write to the whole of the bead 114 with a single bit - see insert.

As far as the drive is concerned, a single bit, 1 or 0, is written in a long sequence. This may be carried out for example using a reformat or erase command.

Reference is now made to Fig. 6B which illustrates a prototype of the device in Fig. 6A according to the present embodiments. The prototype 113 consists of a beaker 115 that does not rotate but instead a stirrer 117 is provided to produce the effect of rotation. The writing heads (not shown) are located at the base of the beaker. A second embodiment for making the artificial monopoles relates to adsorption of BaFe using different chemistries. Adsorption may be carried out by chemically modifying only one pole before adsorption, or by modifying BaFe and then magnetizing using PMRs.

In the first case, of modifying only one pole prior to adsorption, reference is made to Fig. 7, which is a simplified flow chart in which nano-particles of Ba-ferrite are flattened 20 on a surface such that all the particles are magnetized in the same direction. Then 22 a chemical modification of one side of the particle is carried out, e.g. with amino termini.

The particles are then released 24 and exposed in solution 26 to micro-beads covered with another functional group such as carboxylic termini, and a chemical bond may be formed between the magnetic Nano-particles and the beads.

Reference is now made to Fig. 8, which is a simplified diagram showing three different exemplary binding chemistries that may be used for binding the Barium ferrite to the substrate. Reference numeral 60 indicates polymeric acrylic binding. Reference numeral 62 indicates epoxy- based chemistry, and reference numeral 64 indicates a coupling reactions as in EDC-NHS chemistry.

A second case for adsorbing BaFe involves modifying chemically BaFe in a solution, unbound to a surface, and then magnetizing using PMR’ s as before in order to align the spins across the beads to the same direction.

The magnetization process is the same as in the previous case. Fig. 4 illustrates the magnetization process on the particles, and Figs. 6A and 6B illustrate how magnetization may be carried out using a magnetic recording head.

Reference is now made to Figs 9A and 9B, which illustrate an embodiment involving the formation of micro-quadrupol es . Fig. 9A shows a method of making magnetic particles by alignment on a flat substrate and binding back-to-back to form micro-quadrupoles. In stage 40 a thin substrate is coated with a thin layer of PM A, for example a monolayer of BaFe nanoparticles or sputtered layers presenting a PMA behavior, which are magnetized out-of-plane and in the same direction 42. Then the substrates are bound back-to-back 43 and then cut 44 to particles of say size 1-1000 microns in diameter. Hence, the particle produced may present the same magnetization to the environment on its two sides.

Fig. 9B shows the particles aligned in the up-down direction. A back to back quadrupole uses a dual sided acrylic tape where it is easy to adsorb the nanoparticles such that all spins are pointing out of the plane. The tape is then diced into microbeads, for example using an ultrafme shredder or a dicer.

Reference is now made to Fig. 10, which is a simplified flow chart illustrating how 2D monopolar particles may be made by Sputtering in a pre-lithography technique on magnetic beads.

In this approach, a pre-lithographed wafer is provided -50. Deposition of a ferromagnetic layer is carried out 52 by sputtering on the pre-lithographed wafer. The layer is then magnetized 54 and removed to form particles of 1-1000 microns in size -56.

Reference is now made to Fig. 11, which illustrates an exemplary microbead as manufactured using chiral-induced spin selectivity (CISS) manufacture. The core 25 is a silica bead of micron size, say 2 - 25 microns, and the shell is made up of superparamagnetic FeO nanoparticles 27. The FeO nanoparticles are bound to the microbead via a chiral molecule 29, such that the chiral molecule will have two functional binding groups: one attached selectively to the microbead and one attached selectively to the FeO nanoparticle. This may result in a well-organized molecular structure in which the spins within the chiral molecules magnetize the FeO nanoparticles in the same direction. Hence, the magnetization of the FeO nanoparticles can be tuned by the type and handedness of the chiral molecules used.

Reference is now made to Fig. 12, which is a simplified diagram showing a spherical and dipolar magnetic structure built over a microsphere 80. A north polar alignment 82 is provided on one side and a south polar alignment 84 on the other side. One of the poles - here the south pole 84 - is buried in a passivation layer 86 and thus blocked from the point of view of the outside world.

In Fig. 12, the BaFe coated microbeads 80 may be constructed in the form of a dipole in which one pole 82 is exposed and the other 84 is covered by a non-magnetic layer 86, hence providing a single active pole. Here, the BaFe coated beads are primarily dispersed on a carrier (such as a wafer) which may carry some adhesion layer. Then the surface is inserted into a magnetizing machine in order to magnetize the particles. The magnetization field may be above the coercive field of the BaFe. The surface may then be coated by deposition of a thin overlayer film of a non-magnetic material such as non-magnetic metals, dielectrics or Teflon. The particles may eventually be released from the surface by a soft process. The resulting bead may thus present a single active pole whereas the other is hidden.

There are several options for examining and testing the magnetization of these particles. Among them are various optical measurements, such as optical rotation in the magneto optic Ken- effect in which the light reflected from a magnetized material has a slightly rotated plane of polarization. Another option is to use the phenomenon of circular dichroism spectroscopy.

Some further options for measuring the rate of magnetization across the beads involves introducing the particles to a set of micro-scale Hall probes, utilize magnetoresistive devices using a superconducting quantum interference device (SQUID) magnetometer, and magnetic AFM

(MFM).

It is expected that during the life of a patent maturing from this application many relevant coating, deposition, magnetization and other writing technologies will be developed and the scopes of the corresponding terms are intended to include all such new technologies a priori.

The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to".

The term“consisting of’ means“including and limited to”.

As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment, and the text is to be construed as if such a single embodiment is explicitly written out in detail. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention, and the text is to be construed as if such separate embodiments or subcombinations are explicitly set forth herein in detail.

Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety.