Magnetic iron oxide nanoparticles and methods of making the same

Abstract

This invention relates to magnetic iron oxide nanoparticles (NPs), and to methods of making the magnetic iron oxide nanoparticles (NPs) with tunable particle sizes and crystallite size. More specifically, this invention provides methods for making highly crystalline iron oxide nanospheres (IONSs) that exhibit enhanced ferrimagnetic (FM) properties. In addition, the method allows precise modulation of the nanoparticle crystallinity, which in turn enables the ability to finely tune their magnetic properties from ferrimagnetic (FM) properties to superparamagnetic (SPM) properties.

Description

MAGNETIC IRON OXIDE NANOPARTICLES AND METHODS OF MAKING THE SAMECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 546,062 filed October 27, 2023, U.S. Provisional Patent Application No. 63 / 571,111 filed March 28, 2024, and U.S. Provisional Patent Application No. 63 / 655,753 filed June 4, 2024, the contents of each of which are incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under Grant Nos. FA9550-20- 1-0349 and FA9550-23-1-0581 awarded by the U.S. Air Force Office of Scientific Research. The government has certain rights in the invention.FIELD OF THE INVENTION

[0003] This invention relates to magnetic iron oxide nanoparticles (NPs), and to methods of making the magnetic iron oxide nanoparticles (NPs) with tunable particle sizes and crystallite sizes. More specifically, this invention provides methods for making highly crystalline iron oxide nanospheres (IONSS) that exhibit enhanced ferrimagnetic (FM or FiM) properties. In addition, the method allows precise modulation of the nanoparticle crystallinity, which in turn enables the ability to finely tune their magnetic properties from ferrimagnetic (FM or FiM) properties to superparamagnetic (SPM) properties.BACKGROUND

[0004] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information providedherein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0005] For magnetic iron oxide nanoparticles (NPs) in the single domain to multi-domain particle size ranges, synthesizing highly crystalline structures with large crystallite sizes and precisely controlling the crystallinity (crystallite size / grain size) of the NPs remain formidable challenges. To date, the inability to overcome these challenges has limited the utility of magnetic iron oxide nanoparticles (NPs) across a broad range of applications. Therefore, there is an ongoing need for new and improved methods of making magnetic iron oxide nanoparticles (NPs) that overcome these challenges. The embodiments of the present invention address these needs.SUMMARY OF THE INVENTION

[0006] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure. In some embodiments, the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure. In some embodiments, the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm. In some embodiments, the iron oxide is FesCU, or Fe20s, or combination thereof. In some embodiments, the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof. In some embodiments, the magnetic nanoparticle has a magnetic saturation(Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g. In some embodiments, the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a coreshell structure; and wherein the magnetic nanoparticle does not have a core-shell structure. In some embodiments, the particle size is 19 nm to 207 nm. In some embodiments, the polyhedral shape is a cuboid shape. In some embodiments, the iron oxide is FesCU, or Fe20s, or combination thereof. In some embodiments, the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0007] In various embodiments, the present invention provides a method for preparing a magnetic nanoparticle of the present invention, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, stirring the second mixture at a given speed; and heating the second mixture at a given rate. In some embodiments, the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous. In some embodiments, the method further comprises adding an amount of water to the second mixture. In some embodiments, the method further comprises adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0008] In various embodiments, the present invention provides a method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of the present invention, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magneticnanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

[0010] FIG. 1 depicts in accordance with various embodiments of the invention, using different additives in modified solvothermal synthesis to control the crystallinity and magnetic properties of iron oxide nanoparticles.

[0011] FIG. 2 depicts in accordance with various embodiments of the invention, synthesis procedure for highly crystalline iron oxide nanospheres.

[0012] FIG. 3A - FIG. 3F depicts in accordance with various embodiments of the invention, SEM images at lOOkX magnification of highly crystalline FesCU nanospheres with average diameters (particle sizes): (FIG. 3A) 52 nm ± 3 nm, (FIG. 3B) 98 nm ± 8 nm, (FIG. 3C) 120 nm ± 9 nm, (FIG. 3D) 175 nm ± 13 nm, (FIG. 3E) 220 nm ± 10 nm, (FIG. 3F) 393 nm ± 27 nm.

[0013] FIG. 4 depicts in accordance with various embodiments of the invention, XRD patterns of highly crystalline IONSS with average particle sizes of 52 nm, 120 nm, 220 nm, and 392 nm synthesized from EG / DEG (mL) mixtures: 10 / 30, 15 / 25, 20 / 20, and 30 / 10.

[0014] FIG. 5 depicts in accordance with various embodiments of the invention, high- resolution TEM and SAED of IONSs (avg. particle size 120 nm ± 9 nm, cs 37 nm).

[0015] FIG. 6 depicts in accordance with various embodiments of the invention, XPS spectrum of highly crystalline IONSs and image of IONSs powder.

[0016] FIG. 7A - FIG. 7H depicts in accordance with various embodiments of the invention, TEM images of FesO4 nanocubes with various particle sizes (edge length): (FIG. 7A) 43 nm ± 3 nm, (FIG. 7B) 51 nm ± 3 nm, (FIG. 7C) 58 nm ± 4 nm, (FIG. 7D) 69 nm ± 5 nm, (FIG. 7E) 82 nm ± 5 nm, (FIG. 7F) 101 nm ± 17 nm, (FIG. 7G) 119 nm ± 15 nm, and (FIG. 7H) 184 nm ± 23 nm.

[0017] FIG. 8A - FIG. 8E depicts in accordance with various embodiments of the invention, SEM images at 100 kX magnification of IONSS with similar average particle sizes: (FIG. 8A) 157 nm ± 8 nm (cs 37 nm), (FIG. 8B) 160 nm ± 10 nm (cs 26 nm), (FIG. 8C) 159 nm ± 14 nm (cs 19 nm), (FIG. 8D) 159 nm ± 11 nm (cs 12 nm), and (FIG. 8E) 159 nm ± 21 nm (cs 10 nm).

[0018] FIG. 9 depicts in accordance with various embodiments of the invention, high- resolution Fe 2p XPS spectrum of IONSs synthesized from anhydrous NaAc and with varying amounts of Na-acrylate.

[0019] FIG. 10A - FIG. 10F depicts in accordance with various embodiments of the invention, SEM images of IONSs with similar average particle size but having different crystallite sizes: (FIG. 10A) 175 nm ± 13 nm (cs 34 nm), (FIG. 10D) 175 nm ± 11 nm (cs 15), (FIG. 10B) 220 nm ± 10 nm (cs 26), (FIG. 10E) 235 nm ± 15 nm (cs 12), (FIG. 10C) 393 nm ± 27 nm (cs 24), (FIG. 10F) 375 nm ± 37 nm (cs 10 nm). Magnification 100 kX (FIG. 10A, FIG. 10D, FIG. 10B, FIG.10E) and 60 kX (FIG. 10C, FIG. 10F).

[0020] FIG. 11 depicts in accordance with various embodiments of the invention, mechanism of polycrystalline iron oxide nanospheres formation.

[0021] FIG. 12 depicts an embodiment of the invention.

[0022] FIG. 13 depicts in accordance with various embodiments of the invention, IONSs synthesized with slow stirring speed at 250 rpm.

[0023] FIG. 14 depicts in accordance with various embodiments of the invention, TEM image of Fe3O4 nanocubes with average particle size 23 nm ± 4 nm.

[0024] FIG. 15A - FIG. 15B depicts in accordance with various embodiments of the invention, (FIG. 15 A) High-resolution TEM image and (FIG. 15B) SAED patterns of iron oxide nanocubes particle size 100 nm.

[0025] FIG. 16 depicts in accordance with various embodiments of the invention, high- resolution Fe 2p XPS spectra of FeiO nanocubes.

[0026] FIG. 17 depicts in accordance with various embodiments of the invention, particle coercivity versus particle size. Dspis superparamagnetic particle size. DSD is single domain particle size. Adapted from Klabunde, K. J.; Richards, R. M. Nanoscale Materials in Chemistry., John Wiley & Sons, 2009.

[0027] FIG. 18A - FIG. 18B depicts in accordance with various embodiments of the invention, VSM data of samples presented in (FIG. 18A) ferrimagnetic IONSS with crystallite size of 37 nm, 26 nm, 19 nm, and (FIG. 18B) superparamagnetic IONSs with crystallite size 12 nm and10 nm.

[0028] FIG. 19A - FIG. 19B depicts in accordance with various embodiments of the invention, VSM data of samples presented in FIG. 19A ferrimagnetic IONSs with crystallite size from 24 nm to 34 nm, and (FIG. 19B) superparamagnetic IONSs with crystallite size from 10 nm to 15 nm.

[0029] FIG. 20A - FIG. 20E depicts in accordance with various embodiments of the invention, Zero-field-cooling / Field-cooling (ZFC / FC) measurements at field 500 Oe of samples: (FIG. 20A) avg. particle size 159 nm ± 21 nm, cs 10 nm, (FIG. 20B) avg. particle size 159 nm ±11 nm, cs 12 nm, (FIG. 20C) avg. particle size 175 nm ± 11 nm, cs 15 nm, (FIG. 20D) avg. particle size 235 nm ± 15 nm, cs 12 nm, and (FIG. 20E) avg. particle size 375 nm ± 37 nm, cs 10 nm.

[0030] FIG. 21 A - FIG. 2 IF depicts in accordance with various embodiments of the invention, Scale Up Twice to Synthesize Iron Oxide Nanoparticles with Tunable Sizes and Crystallite Sizes.

[0031] FIG. 22 depicts various embodiments of the invention.

[0032] FIG. 23A - FIG. 23B depicts in accordance with various embodiments of the invention, (FIG. 23 A) XPS spectrum with an optical image of nanoparticle powder and (FIG. 23B) Raman spectrum of highly crystalline IONSs.

[0033] FIG. 24 depicts in accordance with various embodiments of the invention, M-T curves at field 20 Oe of superparamagnetic sample size 235 ± 15 nm with cs 12 nm.

[0034] FIG. 25A - FIG. 25D depicts in accordance with various embodiments of the invention, (FIG. 25A) M-H hysteresis loop at 2K and M-T curves at different applied fields (FIG. 25B) 200 Oe, (FIG. 25C) 1000 Oe, and (FIG. 25D) 2000 Oe of superparamagnetic IONSs (size 235 ± 15 nm, cs 12 nm).

[0035] FIG. 26 depicts in accordance with various embodiments of the invention, Raman spectra of IONSs synthesized from scaling-up experiment.

[0036] FIG. 27 depicts in accordance with various embodiments of the invention, XRD patterns of highly crystalline IONSs with average particle sizes of 52 nm, 120 nm, 220 nm, and 393 nm synthesized from EG / DEG (mL) mixtures: 10 / 30, 15 / 25, 20 / 20, and 30 / 10DETAILED DESCRIPTION OF THE INVENTION

[0037] All references cited herein are incorporated by reference in their entirety as though fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0038] One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, various features of embodiments of the invention. Indeed, the present invention is in no way limited to the methods and materials described. For purposes of the present invention, the following terms are defined below. For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here.

[0039] Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. Unless explicitly stated otherwise, or apparent from context, the terms and phrases below do not exclude the meaning that the term or phrase has acquired in the art to which it pertains. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such can vary. The definitions and terminology used herein are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims.

[0040] As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, systems, articles of manufacture, apparatus, and respective component(s)thereof, that are useful to an embodiment, yet open to the inclusion of unspecified elements, whether useful or not. It will be understood by those within the art that, in general, terms used herein are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). Although the open- ended term “comprising,” as a synonym of terms such as including, containing, or having, is used herein to describe and claim the invention, the present invention, or embodiments thereof, may alternatively be described using alternative terms such as “consisting of’ or “consisting essentially of.”

[0041] Unless stated otherwise, the terms “a” and “an” and “the” and similar references used in the context of describing a particular embodiment of the application (especially in the context of claims) can be construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (for example, “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the application and does not pose a limitation on the scope of the application otherwise claimed. The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.” No language in the specification should be construed as indicating any nonclaimed element essential to the practice of the application.

[0042] “Optional" or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not.

[0043] In some embodiments, the numbers expressing quantities of reagents, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon thedesired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0044] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0045] In various embodiments, compounds of the present invention as disclosed herein may be synthesized using any synthetic method available to one of skill in the art. Non-limiting examples of synthetic methods used to prepare various embodiments of compounds of the present invention are disclosed in the Examples section herein.

[0046] Chapter 1

[0047] For magnetic iron oxide nanoparticles (NPs) in the single domain to multi-domain particle size ranges, synthesizing highly crystalline structures with large crystallite sizes and precisely controlling the crystallinity (crystallite size / grain size) of the NPs remain formidable challenges. Herein, we present a facile synthetic method capable of yielding highly crystalline iron oxide nanospheres (IONSS) exhibiting enhanced ferrimagnetic (FM) properties and allowing for precise modulation of their crystallinity, thereby finely tuning their magnetic properties from FM to superparamagnetic (SPM) properties. By employing specific quantities of sodium acetate and water, we surprisingly and successfully synthesized IONSs with a highly crystalline FesO4 phase, exhibiting average particle sizes ranging from 50 nm to 390 nm, with individual crystallite sizes ranging from 24 nm to 37 nm. Surprisingly, these results are accompanied by enhanced FM properties. Subsequently, we conducted a magnetic comparison with well-known FesO4nanocubes. This comparative analysis served to rationalize the enhanced FM properties of the IONSS, attributable to their highly crystalline structure. Furthermore, the introduction of additives such as anhydrous sodium acetate or sodium acrylate surprisingly effectively reduced crystallite sizes, facilitating the production of IONSs with tunable levels of crystallinity. Consequently, by controlling crystallite size while maintaining a consistent average particle size, we were able to finely manipulate the magnetic properties of the IONSs from FM to SPM regimes. The work disclosed herein underscores the pivotal role of crystallite size in governing the magnetic properties of IONSs. In addition, growing mechanism of NPs were proposed to explain the experimental outcomes. In sum, our comprehensive synthetic approach offers a viable means to produce IONSs with tailored magnetic properties, thereby serving as an indispensable tool for the design and fabrication of magnetic iron oxide nanoparticles with specific attributes for applications in sensing, electronic devices, energy systems, environmental remediation, and biomedical technologies.

[0048] Iron oxide nanoparticles have been extensively studied and have demonstrated great potential in various applications, including environmental uses, sensing technologies, waveabsorbing materials, and, notably, biomedical applications such as biosensing, magnetic hyperthermia, IR-induced phototherapy, magnetic contrast agents, and targeted drug delivery. The primary impetus driving intensive research and discovery in this field is rooted in their unique combination of properties, which includes eco-friendliness, cost-effectiveness, biocompatibility, half-metallicity, and diverse magnetic characteristics. To develop high-performance systems of iron oxide nanoparticles (IONPS) tailored for specific applications, the design and fabrication of magnetic IONPs with precise control over particle size, crystallite size, shape, and desired magnetic properties constitute critical steps. Consequently, the development of synthetic methods capable of achieving such control, while ensuring monodisperse size distribution and excellent reproducibility, remains an essential mission for both fundamental and applied science.

[0049] With great potential across diverse fields of application, iron oxide nanoparticles (IONPs) have been synthesized in various sizes and shapes, displaying a wide range of magnetic properties from superparamagnetic (SPM) to ferrimagnetic (FM). In addition to the challenge of synthesizing IONPs with consistent particle size and shape, achieving gram-scale production and enhancing the reproducibility of the synthetic process have become focal points for numerous research groups in recent years. Among the various structures of IONPs, spherical iron oxidenanoparticles have garnered the most attention. Syntheses have produced particles spanning particle sizes from 4 nm to even 1 pm. Typically, iron oxide nanospheres (IONSS) with particle sizes smaller than 25 nm exhibit a single crystal structure and possess SPM properties. Given the notable potential of SPM IONPS in biomedical applications, extensive research efforts have been directed toward gaining a mechanistic understanding, significantly advancing the control and reliability of synthesis to achieve IONPs with desired sizes, compositions, and magnetic properties. Consequently, the scope for further enhancing the performance or properties of these small-sized IONSs (particle size < 25 nm) depends on the design of target applications and the strategies employed for functionalization.

[0050] On the other hand, iron oxide nanospheres (IONSs) larger than single-domain particle size (diameter > 25 nm) typically exhibit polycrystalline structures and display a broader range of magnetic behaviors, including superparamagnetic (SPM) or ferrimagnetic (FM) properties. In the case of these polycrystalline IONSs with particle sizes exceeding 25 nm, their growth initiates with the formation of primary crystals followed by the agglomeration of these primary crystals to form larger particles. Consequently, the magnetic properties of these particles are primarily influenced by two structural parameters: the average diameter of the particle (also referred to as particle size) and the crystallite size (also referred to as 'grain size'), which represents the size of the primary crystal. Therefore, the adjustment of these structural parameters, both in terms of particle size and crystallite size, offers an avenue for studying their magnetic behaviors and exploring potential applications, presenting an opportunity for further discovery.

[0051] The solvothermal approach based on an ethylene glycol (EG) solvent system using iron (III) chloride precursors have shown to be the most useful, offering facile synthetic techniques for controlling nanoparticle size. IONSs synthesized via this solvothermal method have been reported to exhibit either ferrimagnetic (FM) or superparamagnetic (SPM) properties. Despite the successful synthesis of IONSs spanning a wide range of particle sizes, achieving precise control over the crystallinity of nanoparticles remains challenging, with crystallite sizes typically being less than 24 nm. Therefore, without being bound by theory, we hypothesized that IONSs with larger crystallite sizes (> 24 nm) may exhibit stronger FM properties.

[0052] For FM IONPs, it has been reported in the literature that larger-sized IONSs can yield stronger saturation magnetization. However, predicting the effects of particle size on FM properties, especially coercivity remains challenging. Despite this uncertainty about particle sizeeffects, crystallinity has demonstrated a positive impact on enhancing the magnetic properties of IONPS, including both magnetic saturation (Ms) and hysteresis coercivity (He). In the case of large-sized SPM IONSS, with particle sizes around 280 nm, an increase in grain size (crystallite size) from 5.9 nm to 13.5 nm, while maintaining the average particle size, leads to a monotonic increase in the saturation magnetization of IONSs, ranging from 36.2 emu / g to 67.2 emu / g. Improving crystallinity of IONSs is a key approach to enhance the magnetic properties of nanoparticles and maximize the potential of IONSs in various applications. Furthermore, while enhancing the crystallinity of IONSs can address the need for stronger FM properties of nanoparticles, controlling the crystallite size of IONSs within a broad range represents a more viable strategy for tailoring IONSs with specific desired magnetic properties. Herein, in various embodiments of the present invention, we address these challenges through the method as illustrated in FIG. 1.

[0053] Herein, we present an efficient synthetic approach and method to produce highly crystalline IONSs (with crystallite size exceeding 24 nm) in various particle sizes and to control the crystallinity of IONSs over a wide range (ranging from 37 nm to 10 nm). In various embodiments, by employing NaAc 3H2O in combination with varying binary solvent systems, stirring speeds, and ramping rates, we successfully synthesized FesO4 nanospheres with particle sizes ranging from 52 nm to 390 nm, exhibiting highly crystalline structures and uniform morphology. Comparative analysis between highly crystalline IONSs of the present invention and single-crystal FeiO4 nanocubes revealed significant enhancements in Ms, He, and remnant magnetization (Mr). Notably, the disparity in magnetic saturation (Ms) values between nanospheres and nanocubes was remarkably reduced, bringing them to nearly comparable levels for Ms. While the use of trihydrate sodium acetate was surprisingly important in enhancing the crystallinity of IONSs, employing anhydrous NaAc and sodium acrylate (Na-acrylate) surprisingly demonstrated the capability to reduce crystallinity. This, in turn, facilitated fine control over the crystallite size across a broad range, offering a valuable means of tuning magnetic properties from FM to SPM regime without altering the particle size of IONSs. In addition, the work herein focused on the effects of particle size and crystallinity on the magnetic properties of IONSs, thereby establishing the dominant role of crystallinity. Additionally, mechanistic aspects in growing IONSs with controllable particle sizes and crystallinity are also thoroughly discussed herein. The work disclosed herein provides an efficient synthetic approach and method with thecapacity to fabricate IONSS of desired particle size, crystallite size, and magnetic properties, thereby serving as an indispensable and important tool in designing iron oxide nanoparticle systems for applications in electronic devices, sensing technologies, and biomedical applications. In various embodiments, by employing NaAcGFEO in combination with varying binary solvent systems, stirring speeds, and ramping rates, we successfully synthesized FesCU nanospheres with particle sizes ranging from 52 nm to 393 nm, exhibiting highly crystalline structures and uniform morphology.

[0054] Highly Crystalline Iron Oxide Nanospheres.

[0055] In the context of this disclosure and the present invention described herein, the term particle size, abbreviated as “ps” or “PS”, refers to “average diameter” for spherical nanoparticles and the “average edge length” for cubic nanoparticles. The term “crystallite size” is abbreviated as “cs” or “CS”, denoting the average crystallite size, also known as the “grain size” of polycrystalline nanoparticles. In some embodiments, the average diameter may be abbreviated by the letter “D”. By utilizing different binary solvent systems and controlling empirical parameters such as stirring and ramping rates, highly crystalline IONSs with various particle sizes, from 52 nm to 393 nm, were successfully synthesized. FIG. 3A - FIG. 3F displays the SEM images of highly crystalline IONSs with uniform round shapes and narrow particle size distributions. Larger IONSs appeared to exhibit greater sphericity in their shape. In various embodiments of the present invention disclosed herein, vigorous stirring (at least 540 rpm) was employed, positively impacting the control of particle size and shape homogeneity. In various embodiments, slow stirring speeds led to polydisperse particle size distribution of nanoparticles, as illustrated in FIG. 13.

[0056] XRD was used for phase indexing and to deduce crystallite size of the nanoparticles. FIG.4 presents the X-ray diffraction patterns of highly crystalline IONSs, where strong signals with sharp peaks and high intensity indicate highly crystalline structures. The XRD patterns were matched with the JCPDS 01-088-0315 file. In all samples, clear diffraction peaks were observed at 18.35°, 30.18°, 35.55°, 37.19°, 43.21°, 53.61°, 57.15°, and 62.76°, corresponding to the lattice planes (111), (220), (311), (222), (400), (422), (511), and (440), respectively. The calculated values of the crystallite size were 30 nm, 37 nm, 26 nm, and 24 nm for IONSs with average particle sizes of 52 nm ± 3 nm, 120 nm ± 9 nm, 220 nm ± 10 nm, and 393 nm ± 27 nm, respectively. The studied samples exhibited a highly crystalline structure with crystallite size > 24 nm. Notably, the sample synthesized from 15 / 25 mL EG / DEG (mL) ratio displayed the bestcrystalline structure, and the crystallinity was reduced when more EG was used. In addition, low- intensity peaks at diffraction angles of 71.21°, 74.26°, 75.26°, and 79.24° were clearly visible in sample synthesized from 15 / 25 mL EG / DEG ratio were indexed for (620), (533), (622), and (444), respectively. This further confirmed the highest level of crystallinity in this sample. Despite the well-known effects of solvent mixtures on particle size control, there were no observed effects of solvent compositions on the crystallite size. Our experimental results provide evidence that solvent compositions affect the crystallinity of the sample, and a 15 / 25 mL EG / DEG ratio is an optimal binary solvent ratio for forming a highly crystalline structure.

[0057] The use of trihydrate sodium acetate, instead of its anhydrous version, gave a surprising outcome regarding the level of crystallinity. By introducing varying amounts of water into the EG solvent, particle size of NPs was controlled from 80 nm to 1 pm with crystallite sizes ranging from 15.4 nm to 23.9 nm. Therefore, without being bound by theory, we hypothesized that the water content in NaAc kkO fell within the optimal range for forming larger primary crystals. To confirm this hypothesis, we investigated the effects of water on NP structure where controlled experiments with the addition water to the synthesis were conducted, and the results are presented in Table 1.

[0058] Table 1. Control Experiments Involving Addition of Water and AnhydrousNaAc.

[0059] First, by replacing NaAc S hO with anhydrous NaAc while keeping other parameters unchanged, the particle size of IONSS increases but all samples have much smaller crystallite size (<20 nm). A series of experiments with control amount of water adding on the synthesis were conducted. Instead of using trihydrate chemicals, using anhydrous chemicals with 2.17 g NaAc and adding a similar amount of water to what is contained in trihydrate chemicals (1.43 mL H2O), the particle size and crystallite size showed almost no noticeable change. However, using less water caused an increase in the average particle size and a decrease in crystallite size. Further investigations by adding more water while still using NaAc HiO were conducted. The addition of a small amount of water, such as 180 pL, caused almost no significant changes in particle size and crystallite size for both solvent ratios (20 / 20 and 15 / 25). However, a larger amount of 540 pL induced noticeable changes in particle size and crystallinity. While adding more water led to a decrease in particle size, crystallite size usually increased up to a certain level before decreasing. Without being bound by theory, it can be said that using a larger amount of water reduces the particle size, but the effect on crystallite size is not consistently monotonic. As such, there exists a certain range of water amounts that is optimal for producing large primary crystals (crystallite size).

[0060] To visualize the highly crystalline structure, a sample of IONSs with the largest crystallite size was characterized by Selected Area Electron Diffraction (SAED) in high-resolution TEM. Simulated Fast Fourier Transform (FFT) diffraction patterns were produced using DigitalMicrograph® software from the locations indicated by the insets. FIG. 5 provides anoverview of a single crystal domain where all observable planes have a d-spacing = 0.5 nm, characteristic of the (100) plane. The difference between the theoretical (d(ioo) = 0.485 nm) and the experimental spacing is approximately 3%, which falls within the range of systematic error. The red and green insets show the exact same plane orientation, which is easy to identify by observing the three diffraction patterns having the same crystal orientation. The diffraction patterns, along with XRD patterns, collectively confirmed the highly crystalline nature of the nanoparticles.

[0061] XPS was used to confirm the phase compositions of iron oxide samples. In FIG. 6, the full survey spectra of highly crystalline IONSS display peaks corresponding to Fe 2p, O Is, C Is, and Fe 3p. The high-resolution Fe 2p spectra exhibit peaks at 710.4 eV and 724.1 eV, assigned to Fe 2p3 / 2 and Fe 2pl / 2, respectively. Without being bound by theory, the broaden feature of those two peaks indicated the coexistence of Fe2+and Fe3+. A satellite peak around 718 eV was commonly observed forphase, was absent in the spectra, which confirms the FesCU (magnetite) phase nanoparticles. In addition, color of iron oxides can be used to quickly differentiate the phase purity (Cornell, R. M.; Schwertmann, U. The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses,' lohn Wiley & Sons, 2003). Highly crystalline IONSs appear entirely black, indicating the dominant presence of the magnetite (Fe3O4) phase, as shown in FIG. 6.

[0062] The room-temperature ferrimagnetic properties of IONSs were characterized using VSM. Table 2 summarizes the average particle sizes, crystallite sizes, and regarding parameters of their FM properties (saturation magnetization (Ms), coercivity (Hc), and remnant magnetization (Mr)). The first observed trend is that an increase in crystallite size leads to higher He and Mrvalues. Samples with crystallite size of 24 nm (particle size 393 nm), crystallize size 26 nm (particle size 220 nm), crystallite size 30 nm (particle size 52 nm), and crystallite size 37 nm (particle size 98 nm and particle size 120 nm) exhibited increasing He values, ranging from 16 to 68 Oe, and Mr values, ranging from 3 emu / g to 20 emu / g. He and Mr represent how effectively the nanoparticles resist demagnetization and maintain their magnetic moment. Without being bound by theory it can be concluded that better crystallinity likely enhances the ability to maintain magnetized status and resist demagnetization. For samples with particle sizes of 98 nm and 120 nm, both having a similar large crystallite size of 37 nm, larger particles exhibited slightly stronger magnetism. Without being bound by theory it can be said that when samples are having large crystallite size, larger NPs tend to display stronger magnetic properties.

[0063] Table 2. Magnetic Properties FedE Nanospheres with Large Crystallite Size.

[0064] In the realm of magnetic iron oxide nanoparticles comparative studies have been conducted to explore the differences in magnetic properties and investigate the performance of spherical versus cubic iron oxide NPs in applications such as biosensing and magnetic hyperthermia. Reported studies have shown that cubic iron oxide NPs exhibit superior ferrimagnetic properties compared to their spherical counterparts. In the literature, a comparison between FesCU nanocubes and FesCL nanospheres showed that FesCU nanocubes exhibited significantly higher values of both Ms and He, with Ms values being 1.4-3.0 times greater and He values being 1.1-8.0 times higher than those of FeiCh nanospheres. Therefore, the comparison of the magnetism between highly crystalline IONSS and cubic IONPS was employed to confirm the enhancement in ferrimagnetic properties attributed to the highly crystalline structure of IONSs.

[0065] FIG. 7A - FIG. 7H displays TEM images of Fe3O4 nanocubes ranging from 43 ± 3 nm to 184 ± 23 nm. Those iron oxide nanocubes were then compared with highly crystalline IONSs with same volume or same body-diagonal versus diameter for consistency. Consequently, the body-diagonal of nanocubes, volume of the nanocubes, and estimates of equivalent-volume nanospheres were computed and are presented in Table 3. The ferrimagnetic FesO4 nanocubes with an average particle size of 23 nm ± 4 nm were synthesized to fulfill the comprehensiveness of the study, and a corresponding TEM image is provided in FIG. 14.

[0066] The iron oxide nanocubes were characterized using high-resolution XPS spectra in the Fe 2p region, revealing peaks at 723.9 eV and 710.8 eV, corresponding to the spin-orbit split double peaks of Fe 2pi / 2 and Fe 2p3 / 2 of FesCk Surprisingly, no satellite features were observed in the 718 eV region, as shown in FIG. 16, thereby confirming the absence of the y-Fe2O3 phase. FIG. 15A shows a single crystal and its respective zoom-out view, along with SAED and HRTEM image. The high-resolution image of the nanocubes exhibits clear lattice fringes along the diagonal of cubic surface, featuring a d-spacing d(220) = 0.29 nm, which matches with the value of d(220) = 0.29 nm in JCPDS 01-088-0315 file. It is also important to mention that the particle is a single crystal.

[0067] Table 3. Magnetic Properties of FesC Cubic NPs with Various Particle Sizes.

[0068] The effects of particle size on magnetic properties for FesCh nanocubes are delineated from the data presented in Table 3. The coercivity value follows the known explanation of single domain and multi domain transition, illustrated in FIG. 17. Without being bound by theory, the coercivity value increases as the particle size increases until a certain transition size is reached, at which point the splitting into multiple magnetic domains occurs, inducing a decreasein coercivity. For FesCL nanocubes, the He values increased from 43 Oe to 138 Oe in the particle size range 23 nm - 82 nm, and then decreased for larger particle sizes. An edge length of 82 nm (corresponding to a 142-nm body-diagonal dimension) represents approximately the transition size from single-domain to multi-domain behavior for FesCU nanocubes. Without being bound by theory, the explanation illustrated in FIG. 17 may be used to predict the relationship between particle size and He of magnetic particles, it may not adapt well to polycrystalline magnetic nanoparticles due to the dominant influence of crystallite size. Regarding Ms values, without being bound by theory it can be concluded that larger nanocubes tend to induce slightly higher Ms values Table 3 reveals a gradual increase in Ms from 74 emu / g (particle size 23 nm) to approximately 79 emu / g - 82 emu / g (for nanocubes in the particle size range of 40 nm - 100 nm) and reaching 84 emu / g for the larger nanocubes (particle size > 120 nm). Without being bound by theory, smaller nanocubes, with their higher surface-to-volume ratio, exhibit a greater proportion of surface spins. Therefore, without being bound by theory, the presence of canted surface spins could be a contributing factor that lowers the Ms values for smaller nanocubes, a phenomenon reported to be observed in the Ms values of single-crystal superparamagnetic nanoparticles.

[0069] The magnetic properties of FesCU nanocubes were then compared with those of highly crystalline FesCU nanospheres based on the same volume and same body-diagonal (BD) / diameter. The body-diagonal of the nanocubes was chosen for comparison because it presents the largest dimension of the cubic shape. Calculated values of BD (BD = edge length * 3) and volume (volume = (edge length)3) were specified in Table 3. In addition, iron oxide nanocubes with particle size 43 nm, 69 nm, 82 nm, 101 nm, 119 nm, 184 nm were estimated to correspond to similar volume nanospheres with particle sizes of 53 nm, 86 nm, 102 nm, 125 nm, 148 nm, and 228 nm, respectively. Thus, similar-volume comparisons were conducted for highly crystalline IONSS with average particle sizes: 52 nm ± 3 nm, 89 nm ± 8 nm, 98 nm ± 8 nm, 120 nm ± 9 nm, 140 nm ± 10 nm, 220 nm ± 10 nm. Similarly, Table 5 was made by comparison based on similar body-diagonal / diameter basis.

[0070] From those two comparisons, without being bound by theory, a general conclusion emerges: the values of Ms, He, and Mr for FesCU nanocubes are 1.0 to 1.15 times, 1.29 to 2.76 times, and 1.05 to 3.4 times higher than those of highly crystalline IONSs, respectively. In some literature reports, a remarkable difference between nanocubes and nanospheres were observed, which were 1.4 - 3.0 times higher for Ms values and 1.1 - 8.0 times higher for He values. Thesignificant disparity in ferrimagnetic properties between cubic and spherical shapes has been diminished, thanks to the highly crystalline structure of FeaCh nanospheres. The capability of being magnetized (represented by Ms) of IONSS is now almost comparable to that of cubic shapes, with maximum difference < 15%. Without being bound by theory, crystallinity appears to be a crucial factor in enhancing the Ms of magnetic iron oxide NPs. A more prominent difference in He and Mr values were observed, which presented the capability in resist demagnetization and maintain permanent magnetism of FeaCh nanocubes is remarkably better than the spherical shape. Without being bound by theory, magnetic anisotropy includes magneto-crystalline anisotropy and shape anisotropy were expected to be the main contributing factors for those differences in He and Mr. The latter factor was observed when comparing cubic shape versus spherical shape. Without being bound by theory, the first factor (magneto-crystalline anisotropy) could be linked to the alignment of preferential magnetization directions due to the cubic symmetry originating from the magnetite phase (cubic crystal structure) and the cubic shape of the particles.

[0071] Table 4. Magnetic Properties of FeaCh Cubic and Spherical NPs Having Comparable Volumes.

[0072] Table 5. Magnetic Properties of Feath Cubic and Spherical NPs Having Similar Body-Diagonals / Diameters.

[0073] Effects of Crystallite Sizes on Magnetic Properties.

[0074] The crystallite size of poly crystalline IONSS plays an important role in determining the magnetic properties of nanoparticles. Therefore, the ability to control crystallinity without altering the average particle size is an important objective for finely tuning magnetic properties. Hence, controlling crystallinity over a broader particle size range could provide a potential solution for tailoring magnetic properties from FM to SPM regimes.

[0075] In various embodiments, provided herein our method enabled the synthesis of various sets of IONSs with different crystallite sizes while keeping the average particle size at approximately 159, 175, 230, and 380 nm. Depending on the crystallite size of the sample, these IONSs exhibited either superparamagnetic or ferrimagnetic properties. Table 6 summarizes the size, crystallite size, and magnetic properties of these IONSs. To demonstrate our ability to finely adjust crystallinity across a wide range, we controlled the crystallite size of IONSs with an average size of 159 nm, ranging from 37 to 10 nm. In various embodiments of the present invention, thework disclosed herein underscores the dominant role of crystallite size in influencing magnetism in a broad range of magnetic behaviors.

[0076] Table 6. Magnetic Properties of IONSS Nanospheres with Same Particle Size but Different Crystallite Sizes.

[0077] FIG. 8A - FIG. 8E displays the SEM image of IONSs with a similar average particle size of approximately 159 nm but with varying crystallite sizes, ranging from 37 nm, 26 nm, 19 nm, 12 nm, to 10 nm. Samples with crystallite sizes of 37 nm and 26 nm, indicating a highly crystalline structure (cs > 24nm), were synthesized using NaAcG EO from a solvent system containing ratios of 15 / 25 and 20 / 20 EG / DEG, respectively. By replicating the synthesis of IONSs particle size 160 nm ± 10 nm (with a cs of 26 nm), an additional amount of sodium acrylate such as 100 mg and 200 mg were introduced to reduce the cs to 19 nm and 10 nm, respectively. While the use of sodium acrylate was efficient in reducing the crystallite size we observed a broader particle size distribution and moderate deformation of the round shape. The sample with a crystallite size of 19 nm was prepared using anhydrous sodium acetate. Samples with crystallite sizes of 10 nm and 12 nm, displaying no magnetic hysteresis loops, exhibited superparamagnetic-like behavior, and their Ms values are 56 emu / g and 63 emu / g, respectively. The Ms values increase with larger crystallite sizes in SPM NPs are consistent with observationsin literature reports. For those samples with crystallite size of 19 nm, 26 nm, and 37 nm, the FM properties, including Ms, He, and Mr were significantly enhanced with the larger crystallite size. These samples illustrate that, while the NP particle sizes are similar, varying levels of magnetic strength can be achieved by controlling crystallinity. In conclusion, controlling crystallite size was demonstrated to be a useful tool for manipulating the magnetic properties of nanoparticles across a wide range of magnetic strengths and behaviors, encompassing both FM and SPM properties.

[0078] The effects of additives (NaAc, H2O, Na-acrylate) on phase compositions were studied by XPS. Three samples synthesized using anhydrous NaAc or with the addition of sodium acrylate, were subjected to analysis. High-resolution XPS Fe 2p spectra revealed that the sample synthesized with anhydrous NaAc exhibited a satellite peak at 718.7 eV, which indicated the formation of y-Fe2O3 phase. Peaks at 724.1 eV and 710.3 eV were assigned for Fe 2p3 / 2 and Fe 2pi / 2. We also observed a more brown or deep red-brown color of those samples synthesized with anhydrous NaAc, which without being bound by theory suggested the presence of maghemite phase. XPS spectra consistently displayed peaks at around 724.4 eV and 710.8 eV for samples synthesized with sodium acrylate additives, without observation of satellite peaks in the 718 eV region. Therefore, in terms of nanoparticle composition, the use of Na-acrylate additives did not appear to influence the compositions. However, the use of anhydrous sodium acetate led to the formation of the maghemite phase. Despite the fact the co-existence of magnetite (FesCh) and maghemite (y-Fe2O3) have been observed in the literature, the existence of maghemite phase is a contributing factor that lowering the Ms values.

[0079] Three sets of IONSS, each with a similar particle size around 175 nm, 230 nm, and 380 nm, but different in crystallite sizes, were prepared to investigate the effects of crystallinity on their magnetic behaviors. SEM images are presented in FIG. 10A - FIG. 10F, with FIG. 10A, FIG. 10B, and FIG. 10C representing highly crystalline structures, and FIG. 10D, FIG. 10E, FIG.10F indicating lower levels of crystallinity. The samples presented in (FIG. 10A, FIG. 10B, FIG. 10C) with highly crystallite structure possess obvious magnetic hysteresis loop, presented in FIG. 19A. For those samples with small crystallite size (10 nm to 15 nm) in (FIG. 10D, FIG. 10E, FIG. 10F), no magnetic hysteresis loops were observed (FIG. 19B), indicating SPM-like behaviors. These data show that by controlling crystallinity, the magnetic properties of IONSs can be efficiently manipulated in two distinct magnetic regimes: SPM and FM properties.

[0080] SPM iron oxide nanoparticles have been reported in the literature. They typically have an average particle size < 25 nm for iron oxide nanoparticles. The term “superparamagnetic” is commonly used to refer to the room-temperature SPM of magnetic nanoparticles in singledomain particle size range with no hysteresis loop observed at room temperature (Mr=Hc=0). These room -temperature SPM particles should have a blocking temperature < 300 K. The blocking temperature of room-temperature IONSS is characterized using the ZFC / FC protocol, which defines the temperature of the maximum of magnetic moment in ZFC. To date, literature studies have also reported the superparamagnetic properties of iron oxide NPs with large particle size (>100 nm). For example, the assembly of those small SPM NPs into a superparticle with larger particle size (such as 190 nm, 209 nm, 260 nm) through solvophobic interactions have been reported with SPM properties. Additionally, besides the assembly of SPM NPs, literature reports have observed SPM behaviors in large-size poly crystalline NPs (particle size ranging from 100 nm to 280 nm) with small crystallite size of 5 nm to 14 nm). Literature studies have also shown that large IONSs with crystallite sizes reported as > 16 nm typically exhibit ferrimagnetic properties. In this context, the size of primary crystals is trivial in the transition from SPM to FM behavior of large poly crystalline IONSs. In various embodiments of the present invention, IONSs with crystallite size < 15 nm exhibit SPM behaviors, as evidenced by the magnetic hysteresis in room temperature M-H measurements disclosed herein. Despite literature studies reporting the SPM behaviors of large IONSs with small crystallite sizes, the characterization of their blocking temperature using the ZFC / FC protocol has not been reported. Therefore, in various non-limiting embodiments of the present invention, our study as reported herein aims to investigate the blocking temperature of large-sized IONSs exhibiting SPM behaviors.

[0081] FIG. 20A - FIG. 20E presents the magnetization versus temperature (M-T) curves under ZFC / FC protocol for SPM IONSs consisting of small crystallite sizes. Under an applied field of 500 Oe, a large separation between the ZFC and FC magnetization curves was observed for all samples investigated. All the samples show a broaden feature of ZFC M(T) over a measured temperature range of 2 - 400 K with the maxima value of ZFC below 300K. Without being bound by theory, the broaden feature of a ZFC M(T) curve has been attributed in the literature to the presence of particle size distribution and the particle interaction. In various embodiments of the present invention, clustering of primary nanocrystals forms a large particle; each particle can be considered as a multi-spin nanoclusters system. Without being bound by theory, there existmultiple magnetic interactions in a sample that include intra- and inter-particle interactions between nanocrystals within a particle, and interactions among the particles. About the effect of particle size distribution, there are two types of particle size distribution for crystals that form a particle and for all particles within a sample. In addition, without being bound by theory, particle size range difference could be another contributing factor. For example, samples have similar standard deviation of about 10% the mean value, such as large-size particles 200 nm ± 20 nm or small-size particles 20 nm ± 2 nm. The difference in particle size among large particles is in the order of 10 nanometers, while the difference for smaller particles is in the order of few nanometers. Therefore, the broadened feature of the ZFC M(T) curves observed for our samples (FIG. 20A - FIG. 20E) could, without being bound by theory, be attributed to the size distributions of crystals and particles, as well as the coexistence of magnetic interactions within each particle and among particles.

[0082] Proposed Growing Mechanism of Nanoparticles

[0083] Herein, in various embodiments of the present invention we provide the proposed growth mechanism of nanoparticles with the aim of providing guidance for optimizing the synthesis conditions to obtain iron oxide nanospheres (IONSS) with the desired structures and properties. In various embodiments of the present invention, FIG. 11 illustrates the process of IONSs formation. Without being bound by theory, the rate of nucleation and the growth process primarily influence the size of the primary crystals (crystallinity), while the rate at which the primary crystals agglomerate affects the overall size of the particles. Without being bound by theory, Fe3+ions from FeCh precursors initially precipitate as Fe(OH)s or FeOOH intermediates. Subsequently, the partial reduction of Fe3within Fe(OH)3 / FeOOH converts Fe3+to Fe2+, followed by dehydration, ultimately leading to the formation of the Fe CF phase. Ethylene glycol (EG) and diethylene glycol (DEG) can also play important roles as reducing agents, possibly without being bound by theory, converting into aldehydes or carboxylic acids.

[0084] We provide herein below a detailed discussion of the effects of each chemical component in the synthesis process. Without being bound by theory, water is the most critical factor in this mechanism. While an increase in the amount of water consistently led to a reduction in particle size, the crystallite size initially increased to an optimal level and subsequently decreased with further additions of water. An appropriate quantity of water effectively promoted reactions (1), (2), and (4) in FIG. 11, thereby enhancing the rate of nucleation and the growthprocess, leading to the formation of larger primary crystals. However, an excess of H2O could induce the formation of complexes in reaction (6) in FIG. 11 and cause a dilution of the solvent system. This dilution, in turn, reduced the reductive capability of the solvent system (EG & DEG), thus slowing down the nucleation and growth process and giving a smaller crystallite size. Furthermore, H2O played a crucial role in reaction (4) in FIG. 11, facilitating the partial reduction of Fe3+to Fe2+for the formation of the magnetite phase (FesCL). Therefore, without being bound by theory, the formation of the maghemite phase (y-Fe2O3) when using anhydrous sodium acetate can be reasonably understood.

[0085] Without being bound by theory, the particle size of particles is primarily influenced by the rate of the agglomeration process. Nanocrystals grow until they reach a certain size range where the monomer concentration is no longer sufficient to support further growth. At this point, the nanocrystals tend to agglomerate in order to reduce their surface energy. Without being bound by theory, the rate of this agglomeration step is mainly affected by the polarity and viscosity of the solvent system, which are jointly influenced by EG, DEG, and H2O. Bulky molecules with higher boiling points, such as DEG, effectively slow down the process, leading to the formation of smaller particles. Similarly, a higher content of H2O typically dilutes the solution, retarding the agglomeration process and leading to the formation of smaller particles. Moreover, water molecules exhibit a greater affinity for iron cations at the surface compared to EG, DEG, and PEG molecules, owing to their higher polarity and smaller molecular size. Consequently, a relatively small change in the amount of water, on the order of a few hundred pL, can lead to a more significant alteration in particle size compared to changes in the amounts of EG and DEG (Table 1).

[0086] Without being bound by theory, sodium acetate serves as both an alkalinity controller and electrostatic stabilizer for the primary crystals. Without being bound by theory, the presence of sodium acetate is important for the formation of nanocrystals, primarily owing to its capacity to release OH- ions, which facilitate the precipitation of Fe(OH)3. In contrast, without being bound by theory, sodium acrylate contributes less to the system's alkalinity due to the relatively small quantity used (100 mg to 200 mg). Additionally, the acidity of acrylic acid is higher than that of acetic acid, making the conjugated sodium salt less basic than that of acetic acid. Consequently, without being bound by theory, the limited amount of sodium acrylate employed does not significantly impact the particle size of nanoparticles. Furthermore, sodiumacrylate can undergo polymerization to form poly(acrylate) surfactants, without being bound by theory, potentially providing greater steric hindrance for primary crystals. However, without being bound by theory, this could have a detrimental effect, leading to a broader particle size distribution. Nevertheless, the presence of the double bond (H2C=CH-C00(-)) in sodium acrylate may not impede the efficiency of electron transfer for reducing Fe3+to Fe2+. Therefore, withoutbeing bound by theory, the phase composition of the particles is unlikely to be affected. Diethylene glycol (DEG), apart from its role as a solvent and reducing agent, can also act as a surfactant due to structural similarities with polyethylene glycol (PEG). Thus, without being bound by theory, considering DEG as a capping agent helps to explain the smaller particle size when a higher ratio of DEG composition is used. Considering all these complementary factors, without being bound by theory, we postulate that a balance among three components — ethylene glycol (EG), diethylene glycol (DEG), and water (H2O) — is important to maintaining the conditions for forming larger primary crystals, thereby enhancing the crystallinity of the nanoparticles.

[0087] In various embodiments of the present invention, synthesizing IONSS with tunable particle sizes, characterized by highly crystalline structures (crystallite size exceeding 24 nm), and controlling the degree of crystallinity over a broad range has been successfully achieved through a comprehensive synthetic approach described herein. This approach involves the judicious use of various additives (NaAcAFEO, H2O, NaAc anhydrous, and Na-acrylate), precise manipulation of solvent compositions (EG & DEG mixture), and meticulous adjustments to stirring speed and heating rates in the solvothermal synthesis process., Unexpectedly, the work described herein has led to the production of highly crystalline iron oxide nanospheres, accompanied by a significant enhancement in ferrimagnetic properties. Surprisingly, this advancement has effectively narrowed the gap in ferrimagnetic properties between spherical and cubic geometries. Furthermore, the ability to finely control the crystallinity of these IONSs across a wide spectrum has endowed us with a useful and versatile tool for tailoring the magnetic properties of IONSs. While both particle size and crystallinity exert influence over the magnetic properties of IONSs, it is apparent that crystallinity assumes a dominant role. The work disclosed herein proffers a strategic methodology for synthesizing IONPS with desired magnetic properties by finely tuning their dimensions and crystallite sizes. The work disclosed herein provides a useful and versatile approach that holds promise for a myriad of applications, which can, without limitation, be broadly categorized into three distinct types:

[0088] For applications necessitating robust ferrimagnetic properties, such as electronic devices, magnetic recording, and sensing, the utilization of large-sized highly crystalline IONPS with augmented ferrimagnetic properties is particularly promising.

[0089] In the domains of biomedicine, biosensing, and drug delivery, large-sized superparamagnetic IONSS exhibit considerable potential, given their anticipated heightened magnetism within the superparamagnetic regime.

[0090] Lastly, for applications requiring a moderate level of magnetism, such as magnetic separation or recoverable catalysts, the presented methodology represents a suitable tool for customizing magnetism to align with specific application requirements.

[0091] The determination of the primary crystal size (crystallite size) at which the transition from superparamagnetic to ferrimagnetic behaviors occurs, as well as insights into the magnetic behaviors of large superparamagnetic IONSs, including their nano-magnetic characteristics and inter-particle / crystal interactions, poses intriguing fundamental questions.

[0092] In various embodiments the present invention describes a new chemical synthesis method with the ability to control the particle size (diameter of nanoparticles) and the degree of crystallinity (crystallite size / grain size) of magnetic iron oxide nanoparticles, including: 1. Synthesis of highly crystalline iron oxide nanoparticles having a tunably wide range of sizes from 50 to 390 nm diameters with large crystallite size (>24 nm) to enhance their ferrimagnetic (FM) properties. 2. Control the crystallite size of the nanoparticles over a wide range to manipulate the magnetic properties from ferrimagnetic (FM) to superparamagnetic (SPM). This new synthetic approach provides an essential tool to fabricate magnetic iron oxide nanoparticles with desired properties with potential uses in various applications from electronic devices, energy, sensing, environmental remediation, and especially biomedical applications (e.g., magnetic hyperthermia and drug delivery).

[0093] Magnetic iron oxide nanoparticles are attractive nanomaterials with potential applications in diverse fields that include sensing, electronic devices, energy, environment, and biomedicine. To date, for iron oxide nanoparticles in the size range from 50 to 400 nm (diameter), there is no reported method to synthesize highly crystalline nanoparticles and precisely tune their crystallinity over a wide range of crystallite size (10-37 nm). Their highly crystalline structure leads to enhanced ferrimagnetic properties, while the small crystallite size shifts the magnetic properties from ferrimagnetic (FM) to superparamagnetic (SPM). In various embodiments thepresent invention describes our new synthetic approach that enables such tuning of the magnetic properties.

[0094] With our synthetic method, two structural parameters, nanoparticle size and crystallite size, of iron oxide nanoparticles can be independently tailored. First, for applications that require strong magnetic properties (e.g., sensing or electronic devices), the large highly crystalline magnetic nanoparticles are optimal. Second, to fabricate magnetic nanoparticles with specific magnetic properties (either FM or SPM), controlling the crystallinity of the nanoparticles without changing the average size is a useful tool to control the magnetic strength and magnetic properties. Third, large SPM particles with small crystallite sizes (< 15 nm) fabricated using this method are more readily magnetized when compared comparison with small SPM nanoparticles (size < 25 nm). Fourth, the magnetic properties of large SPM nanoparticles offer advantages for those applications that require strong magnetism in SPM regime such as magnetic resonant imaging, magnetic hyperthermia, drug delivery, and magnetic labelling / separation.

[0095] In general, large magnetic iron oxide nanoparticles (diameter above 50 nm), display several advantages such as strong magnetism and diverse magnetic properties (either FM or SPM) when compared to small SPM iron oxide nanoparticles (size < 25 nm). The large magnetic iron oxide nanoparticles have polycrystalline structures both with regard to nanoparticle size and crystallite size (also called grain size), which define their magnetic properties. Among these two factors, crystallite size is the more dominant factor that defines the magnetic behavior (FM vs SPM) and magnetic strength of the nanoparticles. Despite the importance of crystallite size, most prior research has focused on developing synthetic methods to control the size of the nanoparticles. In contrast, our invention offers control over both parameters, including the ability to fabricate highly crystalline iron oxide nanoparticles with crystallite sizes.

[0096] The synthetic method described in various embodiments of the present invention also offers the capacity for industrial for scale up. First, the method is cost-effective and uses readily available starting materials and reagents (i.e., inexpensive commercial chemicals without the need for special storage or preservation). Second, the technical requirements are efficient, requiring only a hotplate / stirrer and a commercial pressure vessel. In our hands without any scale up, each batch of synthesis can produce up to 370 mg of nanoparticles with uniform shape and size. Third, the method is entirely unique in its ability to fabricate highly crystalline magnetic iron oxide nanoparticles with crystallite sizes above 24 nm and offers precise control of the crystallitesize over a wide range, which allows facile tuning of the magnetic properties from ferrimagnetic to superparamagnetic. Fourth, the capacity to control the structural parameters of the magnetic iron oxide nanoparticles can be achieved by adjusting the amounts of the various additives (sodium acetate, sodium acrylate, water), the solvent mixtures (ethylene glycol and diethylene glycol), and the experimental parameters (stirring and ramping rates).

[0097] Magnetic nanomaterials represent a highly promising class of materials for advanced biomedical applications. The synthesis of magnetic iron oxide nanoparticles (NPs) with tailored structures, capable of manifesting desired magnetic properties, is pivotal in enhancing the overall performance of these materials. In this study, we initially focused on fine-tuning the structural parameters of magnetic nanoparticles to modulate their magnetic strength across a wide spectrum of magnetic behaviors. Our investigation unveiled that shape and crystallinity stand as dominant factors in determining the magnetic properties of these materials. Subsequently, we pursued a reverse approach to engineer the structure of magnetic nanomaterials, commencing with the synthesis of their primary nanocrystals and then formulating the assembly of these nanocrystals to form a super-particle structure. We find that the magnetic properties of the materials are primarily governed by the characteristics of their primary crystals. Lastly, we present selected examples showcasing the utility of magnetic nanomaterials in various biomedical applications. These examples underscore the critical significance of controlling the structural parameters of nanomaterials in improving their potential for biomedical advancements.

[0098] Chapter 2

[0099] Iron oxide nanoparticles (IONPS) such as FesCU have been extensively used for biomedical applications ranging from targeted drug delivery to hyperthermia treatment and biodetection, due to their nanoscale size and unique properties. However, the controlled synthesis of IONPs with tunable particle sizes and crystallite / grain sizes to achieve desired magnetic functionalities between single-domain and multi-domain size ranges remains an important challenge. Herein, we present a facile synthetic method capable of producing highly crystalline iron oxide nanospheres (IONSS) with enhanced magnetic properties. First, by adjusting the amounts of sodium acetate and water, we surprisingly and successfully synthesize highly crystalline Fe3O4 IONSs having an average bulk size of 50 nm to 400 nm with individual crystallite sizes above 24 nm. The magnetic properties of these highly crystalline IONSs are comparable to those of their nanocube counterparts, which are generally known to possess superior magneticproperties due to their enhanced crystallinity. Second, by adjusting the additives used, the crystallite size can be tuned widely from 37 nm to 10 nm while maintaining the overall bulk particle size, thereby allowing precise manipulation of their magnetic properties from the ferrimagnetic to the superparamagnetic state. In addition, demonstrations of reaction scale up are presented with the ability to control crystallite size and particle size while retaining their highly uniform structures and morphologies. Based on these findings, the growth mechanism of the IONSS is proposed. Our study highlights the pivotal role of crystal size in controlling the magnetic properties of IONSs and offers a viable means to produce IONSs with magnetic properties desirable for wider applications in sensors, electronics, energy systems, environmental remediation, and biomedicine.

[0100] Iron oxide nanoparticles (lONPs) such as Fe3O4 and y-Fe2O3 have been extensively studied due to their great potential in various applications, including environmental uses, sensing technologies, wave-absorbing materials, and, notably, biomedical applications such as biosensing, magnetic hyperthermia, IR-induced phototherapy, magnetic contrast agents, and targeted drug delivery (Lisjak, D.; Mertelj, A. Anisotropic Magnetic Nanoparticles: A Review of Their Properties, Syntheses and Potential Applications. Prog. Mater. Sci. 2018, 95, 286-328; Bobo, D.; Robinson, K. J.; Islam, J.; Thurecht, K. J.; Corrie, S. R. Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm. Res. 2016, 33, 2373-2387; Liu,S.; Yu, B.; Wang, S.; Shen, Y ; Cong, H. Preparation, Surface Functionalization and Application of FesCU Magnetic Nanoparticles. Adv. Colloid Interface Sci. 2020, 281, 102165; Khizar, S.; Ahmad, N. M.; Zine, N.; Jaffrezic-Renault, N.; Errachid-el-salhi, A.; Elaissari, A. Magnetic Nanoparticles: From Synthesis to Theranostic Applications. ACS Appl. Nano Mater. 2021, 4, 4284-4306; Gavilan, H.; Kumar Avugadda, S.; Fernandez-Cabada, T.; Soni, N.; Cassani, M.;T. Mai, B.; Chantrell, R.; Pellegrino, T. Magnetic Nanoparticles and Clusters for Magnetic Hyperthermia: Optimizing Their Heat Performance and Developing Combinatorial Therapies to Tackle Cancer. Chem. Soc. Rev. 2021, 50, 11614-11667; Tay, Z. W.; Savliwala, S.; Hensley, D. W.; Fung, K. L. B.; Colson, C.; Fellows, B. D.; Zhou, X.; Huynh, Q.; Lu, Y.; Zheng, B.; Chandrasekharan, P.; Rivera-Jimenez, S. M.; Rinaldi-Ramos, C. M.; Conolly, S. M. Superferromagnetic Nanoparticles Enable Order-of-Magnitude Resolution & Sensitivity Gain in Magnetic Particle Imaging. Small Methods 2021, 5, 2100796; Ji, J.; Huang, Y.; Yin, J.; Zhao, X.; Cheng, X.; He, J.; Wang, J.; Li, X ; Liu, J. Electromagnetic Wave Absorption Performance onFesCh Polycrystalline Synthesized by the Synergy Reduction of Ethylene Glycol and Diethylene Glycol. J. Phys. Chem. C 2018, 122, 3628-3637; C. Lavorato, G.; Das, R.; Masa, J. A.; Phan, NEEL; Srikanth, H. Hybrid Magnetic Nanoparticles as Efficient Nanoheaters in Biomedical Applications. Nanoscale Adv. 2021, 3, 867-888; Ge, X.; Mohapatra, J.; Silva, E.; He, G.; Gong, L.; Lyu, T.; Madhogaria, R. P.; Zhao, X.; Cheng, Y.; Al-Enizi, A. M.; Nafady, A.; Tian, J.; Liu, J.P.; Phan, M.-H.; Taraballi, F.; Pettigrew, R. I.; Ma, S. Metal-Organic Framework as a New Type of Magnetothermally-Triggered On-Demand Release Carrier. Small n / a (n / a), 2306940; Thong, P.Q.; Thu Huong, L. T ; Tu, N. D.; My Nhung, H. T.; Khanh, L.; Manh, D. H.; Nam, P. H.; Phuc, N. X.; Alonso, J.; Qiao, J.; Sridhar, S.; Thu, H. P.; Phan, M. H.; Kim Thanh, N. T. Multifunctional Nanocarriers of Fe3O4@PLA-PEG / Curcumin for MRI, Magnetic Hyperthermia and Drug Delivery. Nanomedicine 2022, 77, 1677-1693). The primary impetus driving the intensive research and discoveries is rooted in a unique combination of their properties, including environmental friendliness, cost-effectiveness, biocompatibility, half-metallicity, and diverse magnetic characteristics (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesO4 Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Sci. 2021, 77, 11301; Tran, H.-V.; Ngo, N. M.; Medhi, R.; Srinoi, P.; Liu, T.; Rittikulsittichai, S.; Lee, T. R. Multifunctional Iron Oxide Magnetic Nanoparticles for Biomedical Applications: A Review. Materials 2022, 75, 503). To develop high-performance nanosystems based on lONPs for specific applications, the design and fabrication of highly crystalline IONPS with precise control over particle size, crystalline size, shape, and nanostructures to achieve the desired magnetic properties constitute critical steps (Feld, A.; Weimer, A.; Komowski, A.; Winckelmans, N.; Merkl, J.-P.; Kloust, H.; Zierold, R ; Schmidtke, C.; Schotten, T.; Riedner, M.; Bals, S.; Weller, H. Chemistry of Shape-Controlled Iron Oxide Nanocrystal Formation. ACS Nano 2019, 13, 152-162; Qiao, L.; Fu, Z.; Li, J.; Ghosen, J.; Zeng, M.; Stebbins, J.; Prasad, P. N.; Swihart, M. T. Standardizing Size- and Shape-Controlled Synthesis of Monodisperse Magnetite (FesO4) Nanocrystals by Identifying and Exploiting Effects of Organic Impurities. ACS Nano 2017, 77, 6370-6381; Tian, X.; Ruan, L.; Zhou, S.; Wu, L.; Cao, J.; Qi, X.; Zhang, X.; Shen, S. Appropriate Size of FesO4 Nanoparticles for Cancer Therapy by Ferroptosis. ACS Appl. BioMater. 2022, 5, 1692-1699). Consequently, the development of synthetic methods capable of achieving such control, while ensuring a monodisperse size distribution and excellent reproducibility, remains an essential and challenging task for both fundamental and applied sciences.

[0101] With enormous potential across diverse application fields, IONPS have been synthesized in a variety of sizes and shapes, displaying a wide range of magnetic properties from superparamagnetic (SPM) to ferrimagnetic (FiM) behavior (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesCU Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. AppL Sci. 2021, 77, 11301; Feld, A.; Weimer, A.; Kornowski, A.; Winckelmans, N.; Merkl, J.-P.; Kloust, H.; Zierold, R.; Schmidtke, C.; Schotten, T.; Riedner, M.; Bals, S.; Weller, H. Chemistry of Shape-Controlled Iron Oxide Nanocrystal Formation. ACS Nano 2019, 73, 152-162; Qiao, L.; Fu, Z.; Li, J.; Ghosen, J.; Zeng, M.; Stebbins, J.; Prasad, P. N.; Swihart, M. T. Standardizing Size- and Shape-Controlled Synthesis of Monodisperse Magnetite (FesOQ Nanocrystals by Identifying and Exploiting Effects of Organic Impurities. ACS Nano 2017, 77, 6370-6381; Muro-Cruces, J.; Roca, A. G.; Lopez-Ortega, A.; Fantechi, E.; del-Pozo-Bueno, D.; Estrade, S.; Peiro, F.; Sepulveda, B.; Pineider, F.; Sangregorio, C.; Nogues, J. Precise Size Control of the Growth of FesO4 Nanocubes over a Wide Size Range Using a Rationally Designed One-Pot Synthesis. ACS Nano 2019, 73, 7716-7728; Phan, M.-H.; Alonso, I; Khurshid, H.; Lampen-Kelley, P.; Chandra, S.; Stojak Repa, K.; Nemati, Z.; Das, R.; Iglesias, O.; Srikanth, H. Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems. Nanomaterials 2016, 6, 221). In addition to the challenge of synthesizing IONPs with controlled particle size and shape, achieving gram-scale production and enhancing the reproducibility of the synthesis have been the focus of many research groups in recent years (Kirkpatrick, K. M.; Zhou, B. H.; Bunting, P. C.; Rinehart, J. D. Size-Tunable Magnetite Nanoparticles from Well-Defined Iron Oleate Precursors. Chem. Mater. 2022, 34, 8043-8053; Kampferbeck, M.; Klauke, L. R.; Weller, H.; Vossmeyer, T. Little Adjustments Significantly Simplify the Gram-Scale Synthesis of High-Quality Iron Oxide Nanocubes. Langmuir 2021, 37, 9851-9857; Gavilan, H.; Rizzo, G. M. R.; Silvestri, N.; Mai, B. T.; Pellegrino, T. Scale-up Approach for the Preparation of Magnetic Ferrite Nanocubes and Other Shapes with Benchmark Performance for Magnetic Hyperthermia Applications. Nat. Protoc. 2023, 1-27). Among the various structures of IONPs, spherical IONPs have garnered the most attention, due to ease in synthesis and isotropic magnetic properties. Synthesis has produced particles that range in particle size from 4 nm to even 1 pm (Sun, S.; Zeng, H. Size-Controlled Synthesis of Magnetite Nanoparticles. J. Am. Chem. Soc. 2002, 124, 8204- 8205; Park, I.; An, K.; Hwang, Y.; Park, J.-G.; Noh, H.-L; Kim, J.-Y ; Park, J.-H.; Hwang, N.-M.; Hyeon, T. Ultra-Large-Scale Syntheses of Monodisperse Nanocrystals. Nat. Mater. 2004, 3, 891—895; Deng, H.; Li, X.; Peng, Q.; Wang, X.; Chen, J ; Li, Y. Monodisperse Magnetic Single-Crystal Ferrite Microspheres. Angew. Chem. Int. Ed. 2005, 44, 2782-2785; Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu, W.; Tong, G. Effects of Crystal Size and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse FesCU Microspheres. Mater. Chem. Phys. 2016, 173, 152-160). Typically, iron oxide nanospheres (IONSS) with a diameter or particle size of smaller than 25 nm exhibit a single crystal structure and possess SPM properties. Given the notable potential of SPM IONPS in biomedical applications, extensive research efforts have been directed towards advancing the control and reliability of the synthesis to achieve IONPs with desired sizes, compositions, and magnetic properties (Balakrishnan, T.; Lee, M.-I; Dey, J.; Choi, S.-M. SubNanometer Scale Size-Control of Iron Oxide Nanoparticles with Drying Time of Iron Oleate. CrystEngComm 2019, 21, 4063-4071; Namaware, P. K.; Ravikumar, C. Mechanistic Insights into the Formation and Growth of Anisotropic- Shaped Wiistite-Spinel Core-Shell Iron Oxide Nanoparticles in a Coordinating Solvent. J. Phys. Chem. C 2020, 124, 25010-25027; Chen, R.; Christiansen, M. G.; Sourakov, A.; Mohr, A.; Matsumoto, Y.; Okada, S.; Jasanoff, A.; Anikeeva, P. High-Performance Ferrite Nanoparticles through Nonaqueous Redox Phase Tuning. Nano Lett. 2016, 16, 1345-1351; Unni, M.; Uhl, A. M.; Savliwala, S.; Savitzky, B. H.; Dhavalikar, R.; Garraud, N.; Arnold, D. P.; Kourkoutis, L. F.; Andrew, J. S.; Rinaldi, C. Thermal Decomposition Synthesis of Iron Oxide Nanoparticles with Diminished Magnetic Dead Layer by Controlled Addition of Oxygen. ACS Nano 2017, 11, 2284-2303; Solodov, A. N.; Shayimova, J. R.; Burilova, E. A.; Shurtakova, D. V.; Zhuravleva, Y. I.; Cherosov, M. A.; Tian, Y ; Kiiamov, A. G.; Amirov,R. R. Understanding the Nucleation and Growth of Iron Oxide Nanoparticle Formation by a “Heating-Up” Process: An NMR Relaxation Study. J. Phys. Chem. C 2021, 125, 20980-20992; Chang, H.; Kim, B. H.; Jeong, H. Y.; Moon, J. H.; Park, M.; Shin, K.; Chae, S. I.; Lee, J.; Kang, T.; Choi, B. K.; Yang, J.; Bootharaju, M. S.; Song, H.; An, S. H.; Park, K. M.; Oh, J. Y.; Lee, H.; Kim, M. S.; Park, J.; Hyeon, T. Molecular-Level Understanding of Continuous Growth from Iron- Oxo Clusters to Iron Oxide Nanoparticles. J. Am. Chem. Soc. 2019, 141, 7037-7045; Castellanos- Rubio, L; Arriortua, O.; Iglesias-Rojas, D.; Baron, A.; Rodrigo, I.; Marcano, L.; Garitaonandia, J.S.; Orue, I.; Fdez-Gubieda, M. L.; Insausti, M. A Milestone in the Chemical Synthesis of FesO4 Nanoparticles: Unreported Bulklike Properties Lead to a Remarkable Magnetic Hyperthermia. Chem. Mater. 2021, 33, 8693-8704). Therefore, the scope to further enhance the performance orproperties of these small-sized IONSS (particle size < 25 nm) depends on the design of the target applications and the strategies employed for functionalization.

[0102] On the other hand, larger IONSs (diameter or particle size >25 nm) typically exhibit a poly crystalline structure and display a wider range of magnetic behaviors, including SPM or FiM properties (Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu, W.; Tong, G. Effects of Crystal Size and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse Fe3O4 Microspheres. Mater. Chem. Phys. 2016, 173, 152-160; Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic FesO4 Microparticles. Chem. Mater. 2009, 21, 5079-5087; Chen, Y.; Zhang, J.; Wang, Z.; Zhou, Z. Solvothermal Synthesis of Size-Controlled Monodispersed Superparamagnetic Iron Oxide Nanoparticles. Appl. Sci. 2019, 9, 5157). The growth of these poly crystalline IONSs usually initiates with the formation of primary crystals followed by the agglomeration of these primary crystals to form larger particles (Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic Fe3O4 Microparticles. Chem. Mater. 2009, 21, 5079-5087). Consequently, their magnetic properties are primarily influenced by two structural parameters: the average diameter of the particle (also referred to as particle size) and the crystallite size (also referred to as ‘grain size’). In here, the crystallite size represents for the size of the primary crystal. The tuning of these structural parameters provides an avenue to manipulate their magnetic behaviors and explore potential applications, offering an opportunity for further exploration and discovery.

[0103] The solvothermal approach based on an ethylene glycol (EG) solvent system using iron (III) chloride precursors has proven to be the most useful, offering facile synthetic techniques for controlling nanoparticle size (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesCh Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Sci. 2021, 11, 11301). IONSs synthesized via this solvothermal method have been reported to exhibit either ferrimagnetic (FiM) or superparamagnetic (SPM) properties (Nguyen, M. D.; Tran, H.-V ; Xu, S.; Lee, T. R. Fe3O4 Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Sci. 2021, 11, 11301; Deng, H.; Li, X.; Peng, Q.; Wang, X.; Chen, J.; Li, Y. Monodisperse Magnetic Single-Crystal Ferrite Microspheres. Angew. Chem. Int. Ed. 2005, 44, 2782-2785; Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size ofSuperparamagnetic Fe Ch Microparticles. Chem. Mater. 2009, 21, 5079-5087; Xuan, S.; Wang, F.; J. Wang, Y.-X.; C. Yu, J.; Cham-Fai Leung, K. Facile Synthesis of Size-Controllable Monodispersed Ferrite Nanospheres. J. Mater. Chem. 2010, 20, 5086-5094; Chen, Y.-T.; Medhi, R.; Nekrashevich, I.; Litvinov, D.; Xu, S.; Lee, T. R. Specific Detection of Proteins Using Exceptionally Responsive Magnetic Particles. Anal. Chem. 2018, 90, 6749-6756; Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu, W.; Tong, G. Effects of Crystal Size and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse FeiOi Microspheres. Mater. Chem. Phys. 2016, 173, 152-160; Ge, J.; Hu, Y.; Biasini, M.; Beyermann, W. P.; Yin, Y. Superparamagnetic Magnetite Colloidal Nanocrystal Clusters. Angew. Chem. Int. Ed. 2007, 46, 4342-4345; Kolhatkar, A. G ; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D ; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of FesCU Nanospheres. ACS Omega 2017, 2, 8010-8019). Despite the successful synthesis of IONSS spanning a wide range of particle sizes, achieving precise control over the crystallinity of nanoparticles remains challenging, with crystallite sizes typically being less than 24 nm. Therefore, without being bound by theory, we hypothesized that IONSs with larger crystallite sizes (> 24 nm) may exhibit stronger FiM properties.

[0104] It has been shown that FiM IONSs with larger particle sizes yield higher saturation magnetization (Ms) (Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu, W.; Tong, G. Effects of Crystal Size and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse FesO4 Microspheres. Mater. Chem. Phys. 2016, 173, 152-160; Chen, Y.-T,; Medhi, R.; Nekrashevich, I.; Litvinov, D.; Xu, S.; Lee, T. R. Specific Detection of Proteins Using Exceptionally Responsive Magnetic Particles. Anal. Chem. 2018, 90, 6749-6756). However, the effects of particle size on the other magnetic parameters such as coercivity (He) are not well documented. On the other hand, crystallinity has been reported to enhance the magnetic properties of IONPS, both Ms and He (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesO4 Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Set. 2021, 11, 11301; Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FesO4 Nanocubes Exceeds That of FesO4 Nanospheres. ACS Omega 2017, 2, 8010-8019). In thecase of large-sized IONSS exhibiting SPM properties, with particle sizes around 280 nm, an increase in grain size (crystallite size) from 5.9 to 13.5 nm, while maintaining the average particle size, leads to a monotonic increase in Ms from 36.2 to 67.2 emu / g (Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic FesCU Microparticles. Chem. Mater. 2009, 27, 5079-5087). Recent reports have highlighted the superior magnetic properties of Fe Ch nanocubes compared to their nanosphere counterparts (Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FeaCh Nanocubes Exceeds That of FeaCh Nanospheres. ACS Omega 2017, 2, 8010-8019; Elsayed, W. E. M.; Al-Hazmi, F. S.; Memesh, L. S.; Bronstein, L. M. A Novel Approach for Rapid Green Synthesis of Nearly Mono-Disperse Iron Oxide Magnetic Nanocubes with Remarkable Surface Magnetic Anisotropy Density for Enhancing Hyperthermia Performance. Colloids Surf. A Physicochem. Eng. Asp. 2017, 529, 239-245; Nemati, Z.; Alonso, J.; Rodrigo, I.; Das, R.; Garaio, E.; Garcia, J. A.; Orue, I.; Phan, M.-H.; Srikanth, H. Improving the Heating Efficiency of Iron Oxide Nanoparticles by Tuning Their Shape and Size. J. Phys. Chem. C 2018, 722, 2367-2381). Besides factors related to magnetic anisotropy, crystallinity has been identified as the main determinant of the superior magnetic properties of FeaO4 nanocubes (Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of FesO4 Nanospheres. ACS Omega 2017, 2, 8010-8019). Another literature study reported the examination of two iron oxide suspensions, consisting of NPs with identical size and cubic shapes, and similar dispersion quality, demonstrated significantly enhanced performance in magnetic hyperthermia and magnetic resonance imaging contrast in samples with better crystallinity and no defects (Shingte, S. D.; Phakatkar, A. H.; McKiernan, E.; Nigoghossian, K.; Ferguson, S.; Shahbazian- Yassar, R.; Brougham, D. F. Correlating Magnetic Hyperthermia and Magnetic Resonance Imaging Contrast Performance of Cubic Iron Oxide Nanoparticles with Crystal Structural Integrity. Chem. Mater. 2022, 34, 10801-10810). These findings underscore the critical role of improving the crystallinity of IONSs as a key approach to enhancing their magnetic properties and maximizing their potential in various applications.

[0105] The overall aim of our research is to address the challenges by advancing the solvothermal method through controlling additives used, as illustrated in FIG. 1. Herein, we present here an efficient synthetic approach to produce highly crystalline lONSs with crystal size exceeding 24 nm across broad range of particle size (50 nm to 400 nm) and to control the crystallinity of lONSs over a wide range (from 37 nm to 10 nm). Using NaAc 3H O combined with varying binary solvent systems, stirring speeds, and ramping rates, we successfully synthesized FesCL nanospheres with particle sizes from 52 nm to 390 nm, all of which exhibit highly crystalline structures and uniform morphology. The magnetic properties of these highly crystalline lONSs are comparable with those of the single-crystalline FesCU nanocubes of similar sizes. We found that while the use of trihydrate sodium acetate was instrumental in enhancing the crystallinity of the lONSs, the use of anhydrous NaAc and sodium acrylate (Na-acrylate) reduced the crystallinity. This, in turn, facilitates fine control of crystal size over a wide range, offering a valuable means of tuning magnetic properties from the FiM to SPM state without changing particle size. As described herein, this has been successfully achieved by a comprehensive study of the effects of particle size and crystallinity on the magnetic properties of lONSs. These important findings lead us to propose the growth mechanism of lONSs to achieve adjustable particle sizes and crystallite size. In various embodiments of the present invention, the work described herein introduces an efficient synthetic approach with the capacity to fabricate lONSs of the desired particle size, crystallite size, and magnetic properties, thereby serving as an indispensable tool in the design of IONP systems for applications in electronic devices, sensing technologies, and biomedicine. In various embodiments of the present invention, using NaAcAHiO combined with varying binary solvent systems, stirring speeds, and ramping rates, we successfully synthesized FesCh nanospheres with particle sizes from 52 nm to 393 nm, all of which exhibit highly crystalline structures and uniform morphology.

[0106] RESULTS AND DISCUSSION

[0107] Structural and Magnetic Characterization of Highly Crystalline Iron Oxide Nanospheres.

[0108] In the context of this disclosure and the present invention described herein, the term particle size, abbreviated as “ps”or“PS”, refers to “average diameter” for spherical NPs and the “average edge length” for cubic NPs. The term “crystallite size” is abbreviated as “cs” or “CS”, denoting the average crystallite size, also known as the “grain size” of polycrystalline NPs. Insome embodiments, the average diameter may be abbreviated by the letter “D”. In some embodiments, the term nanoparticle is abbreviated as “NP”. In some embodiments, the term nanoparticles is abbreviated as “NPs”. By utilizing different binary solvent systems and controlling empirical parameters such as stirring and ramping rates, highly crystalline IONSS with various particle sizes, from 52 nm to 393 nm, were successfully synthesized. FIG. 3A - FIG. 3F displays the SEM images of highly crystalline IONSs with uniform round shapes and narrow particle size distributions. Larger IONSs appeared to exhibit greater sphericity in their shape. In various embodiments of the present invention, vigorous stirring (at least 540 rpm) was employed, positively impacting the control of particle size and shape homogeneity. In various embodiments, slow stirring speeds led to polydisperse particle size distribution of NPs, as illustrated in FIG. 13.

[0109] Powder X-ray Diffractometer (XRD) was used for phase indexing and to deduce crystallite size of the NPs. FIG. 4 presents the X-ray diffraction patterns of highly crystalline IONSs, where strong signals with sharp peaks and high intensity indicate highly crystalline structures. The XRD patterns were matched with the JCPDS 01-088-0315 file. In all samples, clear diffraction peaks were observed at 18.35°, 30.18°, 35.55°, 37.19°, 43.21°, 53.61°, 57.15°, and 62.76°, corresponding to the lattice planes (H I), (220), (311), (222), (400), (422), (511), and (440), respectively. The calculated values of the crystallite size were 30 nm, 37 nm, 26 nm, and 24 nm for IONSs with average sizes of 52 nm ± 3 nm, 120 nm ± 9 nm, 220 nm ± 10 nm, and 393 nm ± 27 nm, respectively. The studied samples exhibited a highly crystalline structure with crystallite size > 24 nm. Notably, the sample synthesized from a 15 / 25 mL EG / DEG (mL) ratio displayed the most crystalline structure. And the crystallinity reduced when more EG was used. In addition, low- intensity peaks at diffraction angles of 71.21°, 74.26°, 75.26°, and 79.24° were clearly visible in sample synthesized from a 15 / 25 mL EG / DEG ratio were indexed for (620), (533), (622), and (444), respectively. This further confirmed the highest level of crystallinity in this sample. Despite the well-known effects of solvent mixtures on size control, there were no observed effects of solvent compositions on the crystallite size. Our experimental results provide evidence that solvent compositions affect the crystallinity of the sample, and a 15 / 25 mL EG / DEG ratio is the optimal binary solvent ratio for forming a highly crystalline structure.

[0110] The use of trihydrate sodium acetate, instead of its anhydrous version, resulted in a surprising outcome regarding the level of crystallinity. By introducing varying amounts of water into the EG solvent, particle size of NPs was controlled from 80 nm to 1 pm with reportedcrystallite sizes ranging from 15.4 to 23.9 nm. Therefore, without being bound by theory, we hypothesized that the water content in NaAc- 3H2O fell within the optimal range for forming larger primary crystals. To confirm this hypothesis and investigate the effects of water on NP structure, controlled experiments with the addition water to the synthesis were conducted, and the results are presented in Table 20. First, by replacing NaAcAFFO with anhydrous NaAc while keeping other parameters unchanged, the particle size of IONSS increases but all samples have much smaller crystallite size (<20 nm). A series of experiments with control amount of water adding on the synthesis were conducted. Instead of using trihydrate chemicals, using anhydrous chemicals with 2.17 g NaAc and adding a similar amount of water to what is contained in trihydrate chemicals (1.43 mL H2O), the particle size and crystallite size showed almost no noticeable change. However, using less water caused an increase in the average particle size and a decrease in crystallite size. Further investigations by adding more water while still using NaAc 3H2O were conducted. The addition of a small amount of water, such as 180 pL, caused almost no significant changes in particle size and crystallite size for both solvent ratios (20 / 20 and 15 / 25). However, a larger amount of 540 pL induced noticeable changes in particle size and crystallinity. While adding more water consistently led to a decrease in particle size, crystallite size usually increased up to a certain level before decreasing. Without being bound by theory, it can be said that using a larger amount of water reduces the particle size, but the effect on crystallite size is not consistently monotonic. There exists a certain range of water amounts that is optimal for producing large primary crystals (crystallite size).

[0111] To visualize the highly crystalline structure, a sample of IONSs with the largest crystallite size was characterized by Selected Area Electron Diffraction (SAED) in high-resolution TEM. Simulated Fast Fourier Transform (FFT) diffraction patterns were produced using DigitalMicrograph® software from the locations indicated by the insets. FIG. 5 provides an overview of a single crystal domain where all observable planes have a d-spacing = 0.5 nm, characteristic of the (100) plane. The difference between the theoretical (d(ioo) = 0.485 nm) and the experimental spacing is approximately 3%, which falls within the range of systematic error. The red and green insets show the exact same plane orientation, which is easy to identify by observing the three diffraction patterns having the same crystal orientation. The diffraction patterns, along with XRD patterns, collectively confirmed the highly crystalline nature of the NPs.

[0112] X-ray photoelectron spectroscopy (XPS) was used to confirm the phase compositions of iron oxide samples. In FIG. 6, the full survey spectra of highly crystalline IONSS display peaks corresponding to Fe 2p, 0 Is, C Is, and Fe 3p. The high-resolution Fe 2p spectra exhibit peaks at 710.4 eV and 724.1 eV, assigned to Fe 2p3 / 2 and Fe 2pi / 2, respectively (Yamashita, T.; Hayes, P. Analysis of XPS Spectra of Fe2+and Fe3+Ions in Oxide Materials. Appl. Surf. Sci. 2008, 254, 2441-2449; Grosvenor, A. P.; Kobe, B. A.; Biesinger, M. C.; McIntyre, N. S. Investigation of Multiplet Splitting of Fe 2p XPS Spectra and Bonding in Iron Compounds. Surf. Interface Anal. 2004, 36, 1564-1574). Without being bound by theory, the broadened feature of those two peaks indicated the coexistence of Fe2+and Fe3+. A satellite peak around 718 eV was commonly observed for y-Fe2O3 phase, which was absent in the XPS spectrum (FIG. 6), confirming the synthesized FesCL NPs. In addition, color of iron oxides can be used to quickly differentiate the phase purity (Cornell, R. M.; Schwertmann, U. The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses,' lohn Wiley & Sons, 2003). Highly crystalline IONSs appear entirely black, indicating the dominant presence of the magnetite (Fe3O4) phase, as shown in FIG. 6.

[0113] The room-temperature magnetic properties of the synthesized IONSs were characterized using the VSM. Table 7 summarizes the average particle size, crystallite size, and magnetic parameters (Ms, He, and Mr) of these IONSs. It can be seen in Table 1 that all the IONSs exhibit a FiM behavior (non-zero values of He and Mr) at room temperature. The first observed trend is that an increase in crystallite size leads to higher He and Mr values. Samples with crystallite sizes of 24 nm (particle size, 393 nm), crystallite size 26 nm (particle size, 220 nm), crystallite size 30 nm (particle size, 50 nm), and crystallite size 37 nm (particle sizes, 98 nm and 120 nm) exhibited increases in He (from 16 Oe to 68 Oe) and Mr (from 3 emu / g to 20 emu / g). For samples with a similar crystalline size (37 nm) but different particle sizes (98 nm versus 120 nm), the larger particles are found to possess slightly stronger FiM properties. It is worth noticing that high values of Ms (-70 emu / g) are conserved in FiM poly crystalline IONSs with particle sizes varying over a wide range of ~50 nm to -400 nm, which are desirable for a variety of biomedical and other applications.

[0114] Table 7. Room Temperature Magnetic Properties of Polycrystalline Fe3O4Nanospheres with Large Crystallite Size.

[0115] Highly Crystalline Nanospheres versus Nanocubes: A ComparativeMagnetic Study.

[0116] In the realm of IONP -based biomedical applications, studies have been conducted to compare the magnetic properties of spherical versus cubic IONPS (Kolhatkar, A. G.; Chen, Y - T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, 0.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FesCL Nanocubes Exceeds That of FesCh Nanospheres. ACS Omega 2017, 2, 8010-8019; Elsayed, W. E. M.; Al-Hazmi, F. S.; Memesh, L. S.; Bronstein, L. M. A Novel Approach for Rapid Green Synthesis of Nearly Mono-Disperse Iron Oxide Magnetic Nanocubes with Remarkable Surface Magnetic Anisotropy Density for Enhancing Hyperthermia Performance. Colloids Surf. A Physicochem. Eng. Asp. 2017, 529, 239-245; Nemati, Z.; Alonso, J.; Rodrigo, I.; Das, R.; Garaio, E.; Garcia, J. A.; Orue, I.; Phan, M.-H.; Srikanth, H. Improving the Heating Efficiency of Iron Oxide Nanoparticles by Tuning Their Shape and Size. J. Phys. Chem. C 2018, 722, 2367-2381). It has been shown that the cubic IONPs exhibit superior magnetic properties to their spherical counterparts (Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of Fe3O4 Nanospheres. ACS Omega 2017, 2, 8010-8019; Nemati, Z.; Das, R.; Alonso, J.; Clements, E.; Phan, M. H.; Srikanth, H. Iron Oxide Nanospheres andNanocubes for Magnetic Hyperthermia Therapy: A Comparative Study. J. Electron. Mater. 2017, 46, 3764-3769). In the literature, a comparative analysis of magnetic properties between these two systems revealed that the FesCU nanocubes exhibited significantly higher values of Ms (1.4- 3.0 times) and He (1.1-8.0 times) compared to the FesCU nanospheres (Kolhatkar, A. G.; Chen, Y - T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, 0.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FesCh Nanocubes Exceeds That of FesCh Nanospheres. ACS Omega 2017, 2, 8010-8019). To highlight the enhanced magnetism of the above-synthesized polycrystalline lONSs due to their enhanced crystalline structures and their potential applications, we have compared their FiM properties with those of single-crystalline FesCh nanocubes of similar sizes synthesized by us using the thermal decomposition method (Muro-Cruces, J.; Roca, A. G.; Lopez- Ortega, A.; Fantechi, E.; del-Pozo-Bueno, D.; Estrade, S.; Peiro, F.; Sepulveda, B ; Pineider, F.; Sangregorio, C.; Nogues, J. Precise Size Control of the Growth of FesO4 Nanocubes over a Wide Size Range Using a Rationally Designed One-Pot Synthesis. ACS Nano 2019, 73, 7716-7728; Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of Fe3O4 Nanospheres. ACS Omega 2017, 2, 8010-8019; Kim, D.; Lee, N.; Park, M.; Kim, B. H.; An, K.; Hyeon, T. Synthesis of Uniform Ferrimagnetic Magnetite Nanocubes. J. Am. Chem. Soc. 2009, 131, 454-455).

[0117] FIG. 7A - FIG. 7H displays TEM images of FesCU nanocubes with edge sizes varying from 43 nm ± 3 nm to 184 nm ± 23 nm. These iron oxide nanocubes were then compared with the highly crystalline lONSs of the same volume or the same body-diagonal versus diameter reported in the literature (Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, O.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FesCU Nanocubes Exceeds That of FesCF Nanospheres. ACS Omega 2017, 2, 8010-8019). The body-diagonal and volume of the synthesized FesCh nanocubes, and the estimates of the equivalent-volume nanospheres were computed and are presented in Table 8. The FiM FesCL nanocubes with an average particle size of 23 ± 4 nm were synthesized to fulfill the comprehensiveness of the study, and a corresponding TEM image is provided in FIG. 14.

[0118] The iron oxide nanocubes were characterized using high-resolution XPS spectra in the Fe 2p region, revealing peaks at 723.9 eV and 710.8 eV, corresponding to the spin-orbit split double peaks of Fe 2pi / 2 and Fe 2p3 / 2 of Fea (h . Surprisingly, no satellite features were observed in the 718 eV region, as shown in (FIG. 16), excluding the presence of y-Fe2O3 phase (Yamashita, T.; Hayes, P. Analysis of XPS Spectra of Fe2+and Fe3+Ions in Oxide Materials. Appl. Surf. Sci. 2008, 254, 2441-2449; Grosvenor, A. P.; Kobe, B. A.; Biesinger, M. C.; McIntyre, N. S. Investigation of Multiplet Splitting of Fe 2p XPS Spectra and Bonding in Iron Compounds. Surf. Interface Anal. 2004, 36, 1564-1574). FIG. 15A shows a single crystal and its respective zoom- out view, along with SAED and HRTEM image. The high-resolution image of the nanocubes exhibits clear lattice fringes along the diagonal of cubic surface, featuring a d-spacing d(220) = 0.29 nm, which matches with the value of d(220) = 0.29 nm in JCPDS 01-088-0315 file. It is also important to mention that the nanocube particle is a single crystal.

[0119] Table 8. Magnetic Properties of FeTH Cubic NPs with Various Particle Sizes.

[0120] The effects of particle size on the magnetic properties of FesCB nanocubes are easily delineated from the magnetic data summarized in Table 8. The variation in coercivity follows thattransitions from the single-domain and multi domain regime, illustrated in FIG. 17. Without being bound by theory the He increases as the particle size increases until reaching a critical size, above which the multi-domain state appears to occur, leading to a decrease in coercivity. For the presently synthesized FesCU nanocubes, He increased from 43 Oe to 138 Oe in the particle size range of 23 nm to 82 nm, and then decreased for larger particle sizes. An edge length of 82 nm (corresponding to the 142-nm body-diagonal dimension) represents approximately the critical size for the FerCh nanocubes at which a transition from the single-domain to multi-domain state occurs. Without being bound by theory, it is worth noting that while the plot illustrated in FIG. 17 may be used to predict the relationship between the particle size and He of a magnetic nanoparticle system, it can be adapted to describe the relationship between the crystallite size and He in the polycrystalline IONSS. Regarding Ms values, without being bound by theory, it can be concluded that larger nanocubes tend to yield slightly higher Ms values. Table 8 reveals a gradual increase in Ms from 74 emu / g (particle size 23 nm) to approximately 79 emu / g to 82 emu / g (in the particle size range of 40 nm to 100 nm), reaching 84 emu / g for larger nanocubes (particle size > 120 nm). Without being bound by theory, smaller nanocubes, with their higher surface-to-volume ratio, exhibit a greater proportion of disordered / canted surface spins. Therefore, without being bound by theory, the presence of disordered / canted surface spins could result in lower Ms values in smaller nanocubes, a phenomenon reported to be observed in fine magnetic nanosystems (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesCM Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Sci. 2021, 77, 11301; Xu, Z.; Shen, C.; Hou, Y.; Gao, H.; Sun, S. Oleylamine as Both Reducing Agent and Stabilizer in a Facile Synthesis of Magnetite Nanoparticles. Chem. Mater. 2009, 27, 1778-1780; Lu, A.-H.; Salabas, E. L.; Schiith, F. Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application. Angew. Chem. Int. Ed. 2007, 46, 1222-1244). By analyzing the size-dependent magnetic properties of the Fe3O4 nanocubes, we showed that the relationship established (presented in FIG. 17) for the He vs. particle size dependence is generally valid for NP systems with the single crystalline nature. For the polycrystalline IONSs, however, we have shown that He does not scale with particle size but crystallite size (Table 7). In the next part, we will discuss in detail the relation between He and crystallite size in the polycrystalline IONS system.

[0121] Now the magnetic parameters (Ms, He, and Mr) of the FesO4 nanocubes are compared to those of the FesO4 nanospheres based on the same volume or the same body-diagonal(BD) / diameter (Kolhatkar, A. G.; Chen, Y.-T.; Chinwangso, P.; Nekrashevich, I.; Dannangoda, G. C.; Singh, A.; Jamison, A. C.; Zenasni, 0.; Rusakova, I. A.; Martirosyan, K. S.; Litvinov, D.; Xu, S.; Willson, R. C.; Lee, T. R. Magnetic Sensing Potential of FesCU Nanocubes Exceeds That of FesCU Nanospheres. ACS Omega 2017, 2, 8010-8019). The body-diagonal of the nanocubes was chosen for this comparison because it presents the largest dimension of a cubic shape. Calculated values of BD (BD = edge length * V3) and volume (volume = (edge length)3) of the FesCh nanocubes are provided in Table 8. The nanocubes with particle sizes of 43 nm, 69 nm, 82 nm, 101 nm, 119, nm and 184 nm are estimated to have volumes equivalent to the nanospheres with particle sizes of 53 nm, 86 nm, 102 nm, 125 nm, 148 nm, and 228 nm. Therefore, the similar- volume comparisons are made for the poly crystalline IONSS with average particle sizes of 52 nm ± 3 nm, 89 nm ± 8 nm, 98 nm ± 8 nm, 120 nm ± 9 nm, 140 nm ± 10 nm, and 220 nm ± 10 nm. Table 10 compares the magnetic parameters of these two systems.

[0122] Table 9. Magnetic Properties of Fe.dh Cubic and Spherical NPs Having Comparable Volumes.

[0123] Table 10. Magnetic Properties of FesC Cubic and Spherical NPs Having Similar Body-Diagonals / Diameters.

[0124] It can be seen clearly in this table that values of Ms, He, and Mr for the FesCh nanocubes are 1.0 to 1.15 times, 1.29 to 2.76 times, and 1.05 to 3.4 times higher than those of the FesCh IONSS, respectively. Noticeably, the values of Ms are comparable for both systems, which once again indicates that the high crystallinity in the polycrystalline IONSs is crucial in preserving the large Ms values, and that the polycrystalline IONSs are very promising for a wide range of biomedical applications. More prominent differences in He and Mr are observed in the FesO4 nanocubes compared to the FesO-t IONSs, which arises mainly from the greater contribution of both magnetocrystalline and shape anisotropies in the former (Nguyen, M. D.; Tran, H.-V.; Xu, S.; Lee, T. R. FesO4 Nanoparticles: Structures, Synthesis, Magnetic Properties, Surface Functionalization, and Emerging Applications. Appl. Sci. 2021, 77, 11301; Lu, A.-H.; Salabas, E. L.; Schuth, F. Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application. Angew. Chem. Int. Ed. 2007, 46, 1222-1244).

[0125] Magnetic Tunability from Ferrimagnetism to Superparamagnetism in Iron Oxide Nanospheres: The Importance of Controlling Crystalline Sizes.

[0126] As shown above, the crystallite size of the polycrystalline IONSS plays a crucial role in determining their magnetic properties. Therefore, the ability to control crystallinity without altering the average particle size is crucial to fine-tuning the magnetic properties. A literature study reported the use of sodium acrylate to adjust the crystallite size from 13.5 to 5.9 nm while maintaining an average particle size of around 280 nm (Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham- Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic FesCh Microparticles. Chem. Mater. 2009, 21, 5079-5087). However, the magnetic properties of the IONPS were only limited to the SPM regime. It would therefore be important to investigate how the magnetic properties of polycrystalline IONPs vary from the FiM to SPM state when crystalline size can be tuned around a critical size. In this context, the critical size means the specific size of primary crystals (crystallite sizes) in the polycrystalline IONSs at which the transition from FiM to SPM properties occurs.

[0127] In various embodiments of the present invention provided herein, our synthesis method has enabled us to synthesize IONSs with different crystallite sizes (10 nm to 37 nm) while keeping the average particle size at approximately 160 nm. FIG. 8 A - FIG. 8E displays, for example, the SEM images of IONSs with a similar average particle size of approximately 160 nm but with varying crystallite sizes, ranging from 37 nm, 26 nm, 19 nm, 12 nm, to 10 nm. Here, samples with crystallite sizes of 37 nm and 26 nm, indicating a highly crystalline structure (cs > 24nm), were synthesized using NaAc 3H2O from a solvent system containing ratios of 15 / 25 and 20 / 20 EG / DEG, respectively. By replicating the synthesis of IONSs size 160 nm ± 10 nm (with a cs of 26 nm), an additional amount of sodium acrylate such as 100 mg and 200 mg were introduced to reduce the cs to 19 nm and 10 nm, respectively. While the use of sodium acrylate was efficient in reducing the crystallite size (Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic Fe O4 Microparticles. Chem. Mater. 2009, 21, 5079-5087), we observed a broader particle size distribution and moderate deformation of the round shape. The magnetic properties of these samples were measured using the VSM. Table 11 summarizes the particle size, crystallite size, and magnetic properties of these IONSs. It is very interesting to note in this table that the IONSs undergo a transition from the FiM (He ^0, M 0) to SPM (He =0, Mr— 0) state, when crystalline size is reduced from 37 nm to 10 nm. For samples with crystallite sizes of 19 nm, 26 nm, and 37 nm, the FiM properties are achieved, with values of Ms, He, and Mr increasing with crystallite size. However, samples with crystallite sizes of 10 nm and12 nm, displaying no magnetic hysteresis (He =0, Mr=0), exhibit a SPM-like behavior, and their Ms values are 56 emu / g and 63 emu / g, respectively. The Ms values increase with larger crystallite sizes in these SPM IONSS are consistent with the observations in the literature (Xuan, S.; Wang, Y.-X. J.; Yu, J. C.; Cham-Fai Leung, K. Tuning the Grain Size and Particle Size of Superparamagnetic FeaCh Microparticles. Chem. Mater. 2009, 27, 5079-5087). The critical size of the crystallite size in polycrystalline IONSs at which the FiM to SPM transition occurs, appears to be around 15 nm.

[0128] Table 11. Magnetic Properties of IONSs Nanospheres with Same Particle Size but Different Crystallite Sizes.

[0129] To affirm these findings, three sets of IONSs, each with a similar particle size around 175 nm, 230 nm, and 380 nm, but different in crystallite sizes, were synthesized and characterized to check the effects of crystallinity on the magnetic (FiM vs. SPM) behaviors. FIG. 10A - FIG. 10F contrasts the SEM images of these samples, with FIG. 10A, 10B, and FIG. 10C for the highly crystalline FiM NPs (crystalline size, 26 nm to 34 nm), and FIG. 10D, FIG. 10E,FIG. 10F for the SPM NPs (crystallite size, 10 nm to 15 nm). The samples presented in FIG. 10A, FIG. 10B, FIG. 10C display obvious magnetic hysteresis (FIG. 19A), signalizing the FiM characteristic. The samples presented in FIG. 10D, FIG. 10E, FIG. 10F show no magnetic hysteresis (FIG. 19B), confirming the SPM nature at room temperature. These findings once again underscore the important role of crystallite size in controlling the nano-magnetism in magnetic nanoparticle systems.

[0130] Superparamagnetic Properties of Size-Tunable Polycrystalline IONSS.

[0131] While it is not possible to achieve the SPM behavior in conventionally synthesized IONSs with large particle sizes (> 50 nm), our findings, as reported above herein, demonstrate this possibility in the presently studied polycrystalline IONSs. Indeed, we show in Table 12 that IONSs with crystallite sizes less than 15 nm (the critical SPM-size) exhibit the SPM behavior, their average particle size varies from 160 nm to 380 nm though. The key to maintaining the SPM while tuning the size of NPs relies on the control of crystallite size < 15 nm. The crystallite size of 15 nm is in the single-domain SPM region. Therefore, the SPM characteristic of the large poly crystalline IONSs in the size range of few hundreds of nanometers can be understood as the collective SPM behaviors of their primary crystals whose magnetic interactions within a polycrystalline particle are less significant.

[0132] Table 12. IONSs with SPM Properties in a Wide Range of Particle Size from 160 nm to 380 nm.

[0133] Despite some works reporting the SPM behavior of large IONSs, a clear knowledge of the temperature-dependent magnetization associated with the SPM to FiM transition has not been reached (Xuan, S.; Wang, Y.-X. J.; Yu, I. C ; Cham-Fai Leung, K. Tuning the Grain Size andParticle Size of Superparamagnetic FesCh Microparticles. Chem. Mater. lM9, 21, 5079-5087; Ge, J.; Hu, Y.; Biasini, M.; Beyermann, W. P.; Yin, Y. Superparamagnetic Magnetite Colloidal Nanocrystal Clusters. Angew. Chem. Int. Ed. 2007, - / 6, 4342-4345). Therefore, we conducted magnetization vs. temperature (M-T) measurements under ZFC / FC protocol for the SPM lONSs, which are displayed in FIG. 20A - FIG. 20E. Under an applied field of 500 Oe, a large separation between the ZFC and FC magnetization curves was observed for all samples investigated. All the samples show a broaden feature of ZFC M(T) over a measured temperature range of 2 K to 400 K with the maxima value of ZFC below 300 K. Without being bound by theory, the broaden feature of a ZFC M(T) curve has been attributed to the presence of particle size distribution and interparticle interactions (Xu, W.; Ji, M.; Chen, Y.; Zheng, H.; Wang, L.; Peng, D.-L. Nickel Colloidal Superparticles: Microemulsion-Based Self-Assembly Preparation and Their Transition from Room-Temperature Superparamagnetism to Ferromagnetism. J. Phys. Chem. C 2021, 125, 5880— 5889; Zheng, R. K.; Gu, H.; Xu, B.; Zhang, X. X. The Origin of the Non-Monotonic Field Dependence of the Blocking Temperature in Magnetic Nanoparticles. J. Phys.: Condens. Matter 2006, 18, 5905; Sappey, R.; Vincent, E.; Hadacek, N.; Chaput, F.; Boilot, J. P.; Zins, D. Nonmonotonic Field Dependence of the Zero-Field Cooled Magnetization Peak in Some Systems of Magnetic Nanoparticles. Phys. Rev. B 1997, 56, 14551-14559; Livesey, K. L.; Ruta, S.; Anderson, N. R.; Baldomir, D ; Chantrell, R. W.; Serantes, D. Beyond the Blocking Model to Fit Nanoparticle ZFC / FC Magnetisation Curves. Set. Rep. 2018, 8, 11166; Frey, N. A.; Phan, M. H.; Srikanth, H ; Srinath, S.; Wang, C.; Sun, S. Interparticle Interactions in Coupled Au-FerCh Nanoparticles. J. Appl. Phys. 2009, 105, 07B502).

[0134] In various embodiments of the present invention, clustering of primary nanocrystals forms a large particle; each particle can be considered as a multi-spin nanoclusters system. Without being bound by theory, there thus exist multiple magnetic interactions in each sample, including intra- and inter-particle interactions between nanocrystals within a particle, and interactions among the particles. Effects of size distribution, including size distribution for nanocrystals that form a particle and for all particles within a sample, could also be considerable. For example, samples have similar standard deviation of about 10% of the mean value, such as large-size particles 200 nm ± 20 nm or small-size particles 20 nm ± 2 nm. Therefore, the broadening feature of the ZFC M(T) curves observed for our samples (FIG. 20A - FIG. 20E) can be attributed to the sizedistribution of crystals and particles, as well as multiple magnetic interactions occurring within each particle and among particles.

[0135] Demonstrations for the Scale-Up Synthesis of Polycrystalline IONSS.To demonstrate the capability of method in scaling up, demonstrations for scaling up with double scale produced highly uniform IONSs with tunable particle size and crystallite size were presented in FIG. 21 A - FIG. 21F. The synthesis condition and results were presented in Table 21. The synthesis with double scale was able to produce above 0.8 g of high-quality IONSs. The first two conditions utilized sodium acetate trihydrate at solvent ration 15 / 25 mL and 20 / 20 mL EG / DEG perfectly replicate the result from the original scale reaction. Two samples with the particle size around 180 nm to 190 nm with crystallite sizes of 11 nm and 40 nm were synthesized to demonstrate the capability of tuning the crystallinity. The success of scaling up the reaction was achieved thanks to the effectiveness of the method. By following the same strategy in utilizing solvent compositions, adjusting the amount of water, using different amounts of additives, and controlling experimental parameters (ramping rate, stirring speed) as described in the work provided herein, we envision that producing large scale of uniform IONSs with tunable particle size and crystallite size can be achieved without any forceable challenges.

[0136] Proposed Mechanism of Growth of Polycrystalline Iron Oxide Nanoparticles.

[0137] In this section, we discuss the proposed growth mechanism of NPs with the aim of providing guidance for optimizing the synthesis conditions to obtain iron oxide nanospheres (IONSs) with the desired structures and properties. FIG. 2 illustrates the process of IONSs formation. Without being bound by theory, the rate of nucleation and the growth process primarily influence the size of the primary crystals (crystallite size), while the rate at which the primary crystals agglomerate affects the overall size of the particles. Without being bound by theory, Fe3+ions from FeCh precursors initially precipitate as Fe(OH)3 or FeOOH intermediates. Subsequently, the partial reduction of Fe3+within Fe(OH)3 / FeOOH converts Fe3+to Fe2+, followed by dehydration, ultimately resulting in the formation of the FesCU phase. Ethylene glycol (EG) and diethylene glycol (DEG) also play crucial roles as reducing agents, possibly without being bound by theory, converting into aldehydes or carboxylic acids (Ji, J.; Huang, Y.; Yin, J.; Zhao, X.; Cheng, X.; He, J.; Wang, J.; Li, X ; Liu, J. Electromagnetic Wave Absorption Performance on Fe3O4 Polycrystalline Synthesized by the Synergy Reduction of Ethylene Glycol and Diethylene Glycol. J. Phys. Chem. C 2018, 122, 3628-3637; Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu,W.; Tong, G. Effects of Crystal Size and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse FesCh Microspheres. Mater. Chem. Phys. 2016, 173, 152-160; Wang, Y.; Zheng, Y.; Huang, C. Z.; Xia, Y. Synthesis of Ag Nanocubes 18-32 Nm in Edge Length: The Effects of Polyol on Reduction Kinetics, Size Control, and Reproducibility. J. Am. Chem. Soc. 2013, 135, 1941-1951). We will now delve into a detailed discussion of the effects of each chemical component in the synthesis process.

[0138] The effects of additives (NaAc, H2O, Na-acrylate) on phase compositions were studied by XPS, presented in FIG. 9. Three samples synthesized using anhydrous NaAc or with the addition of sodium acrylate, were subjected to analysis. High-resolution XPS Fe 2p spectra revealed that the sample synthesized with anhydrous NaAc exhibited a satellite peak at 718.7 eV, indicating the formation of y-Fe2C>3 phase (Yamashita, T.; Hayes, P. Analysis of XPS Spectra of Fe2+and Fe3+Ions in Oxide Materials. Appl. Surf. Sci. 2008, 254, 2441-2449). Peaks at 724.1 eV and 710.3 eV were assigned for Fe 2p3 / 2 and Fe 2pi / 2. We also observed a more brown or deep red- brown color of those samples synthesized with anhydrous NaAc, which suggested the presence of maghemite phase (Cornell, R. M.; Schwertmann, U. The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses,' John Wiley & Sons, 2003). XPS spectra consistently displayed peaks at around 724.4 eV and 710.8 eV for samples synthesized with sodium acrylate additives, without observation of obvious satellite peaks in the 718 eV region. Therefore, the use of Na- acrylate additives did not appear to influence the compositions. However, the use of anhydrous sodium acetate led to the formation of the maghemite phase. Despite the fact the co-existence of magnetite (FesC ) and maghemite (y-Fe2O3) are commonly observed, the existence of maghemite phase is a contributing factor that lowering the Ms values (Colombo, M.; Carr egal -Romero, S.; F. Casula, M.; Gutierrez, L.; P. Morales, M.; B. Bohm, I.; T. Heverhagen, J.; Prosperi, D.; J. Parak, W. Biological Applications of Magnetic Nanoparticles. Chem. Soc. Rev. 2012, 41, 4306-4334). In general, the broadening feature of peaks at around 710 eV and 724 eV observed in all samples displayed the co-existence of Fe2+and Fe3+in samples, which indicates the existence of a dominant Fe3O4 phase.

[0139] Without being bound by theory, water is the most critical factor in this mechanism. While an increase in the amount of water consistently led to a reduction in particle size, the crystallite size initially increased to an optimal level and subsequently decreased with further additions of water (Liu, Y.; Cui, T.; Li, Y.; Zhao, Y.; Ye, Y.; Wu, W.; Tong, G. Effects of CrystalSize and Sphere Diameter on Static Magnetic and Electromagnetic Properties of Monodisperse FesCh Microspheres. Mater. Chem. Phys. 2016, 173, 152-160). An appropriate quantity of water effectively promoted reactions (1), (2), and (4), thereby enhancing the rate of nucleation and the growth process, resulting in the formation of larger primary crystals. However, an excess of H2O could induce the formation of complexes in reaction (6) and cause a dilution of the solvent system. This dilution, in turn, diminished the reductive capability of the solvent system (EG & DEG), thus slowing down the nucleation and growth process and resulting in a smaller crystallite size. Furthermore, H2O played a crucial role in reaction (4), facilitating the partial reduction of Fe3+to Fe2+for the formation of the magnetite phase (FesCU). Therefore, the formation of the maghemite phase (y-Fe2O3) when using anhydrous sodium acetate can be reasonably understood.

[0140] Without being bound by theory, the size of particles is primarily influenced by the rate of the agglomeration process. Nanocrystals grow until they reach a certain size range where the monomer concentration is no longer sufficient to support further growth. At this point, the nanocrystals tend to agglomerate in order to reduce their surface energy. Without being bound by theory, the rate of this agglomeration step is mainly affected by the polarity and viscosity of the solvent system, which are jointly influenced by EG, DEG, and H2O. Bulky molecules with higher boiling points, such as DEG, effectively slow down the process, resulting in the formation of smaller particles. Similarly, a higher content of H2O typically dilutes the solution, retarding the agglomeration process and leading to the formation of smaller particles. Moreover, water molecules exhibit a greater affinity for iron cations at the surface compared to EG, DEG, and PEG molecules, owing to their higher polarity and smaller molecular size. Consequently, a relatively small change in the amount of water, on the order of a few hundred pL, can lead to a more significant alteration in particle size compared to changes in the amounts of EG and DEG (Table 20).

[0141] Without being bound by theory, sodium acetate serves as both an alkalinity controller and electrostatic stabilizer for the primary crystals. Without being bound by theory, presence of sodium acetate is essential for the formation of nanocrystals, primarily owing to its capacity to release OH' ions, which facilitate the precipitation of Fe(OH)3. In contrast, without being bound by theory, sodium acrylate contributes less to the system's alkalinity due to the relatively small quantity used (100 to 200 mg). Additionally, the acidity of acrylic acid is higher than that of acetic acid, resulting in the conjugated sodium salt being less basic. Consequently,without being bound by theory, the limited amount of sodium acrylate employed does not significantly impact the size of NPs. Furthermore, sodium acrylate can undergo polymerization to form poly(acrylate) surfactants, without being bound by theory, potentially providing greater steric hindrance for primary crystals. However, without being bound by theory, this could have a detrimental effect, leading to a broader size distribution. Nevertheless, the presence of the double bond (H2C=CH-C00(-)) in sodium acrylate may not impede the efficiency of electron transfer for reducing Fe3+to Fe2+. Therefore, without being bound by theory, the phase composition of the particles is unlikely to be affected. Diethylene glycol (DEG), apart from its role as a solvent and reducing agent, also acts as a surfactant due to structural similarities with polyethylene glycol (PEG). Thus, without being bound by theory, considering DEG as a capping agent explains the smaller particle size when a higher ratio of DEG composition is used. Considering all these complementary factors, without being bound by theory, we postulate that a balance among three components: ethylene glycol (EG), DEG, and H2O is crucial to maintaining the optimal conditions for forming larger primary crystals, thereby enhancing the crystallinity of the NPs.

[0142] Synthesizing IONSS with tunable particle sizes and degree of crystallinity over a broad range has been successfully achieved through a comprehensive synthetic approach. This approach involves the judicious use of various additives (NaAc-3H2O, H2O, NaAc anhydrous, and Na-acrylate), precise manipulation of solvent compositions (EG & DEG mixture), and meticulous adjustments to stirring speed and heating rates in the solvothermal synthesis process. Surprisingly, this endeavor has unexpectedly resulted in the production of highly crystalline iron oxide nanospheres, accompanied by a significant enhancement in FiM properties. Notably, this advancement has effectively narrowed the gap in FiM properties between spherical and cubic geometries. Furthermore, the ability to finely control the crystallinity of these IONSs across a wide range (from 10 nm to 37 nm) has endowed us with a versatile tool for tailoring the magnetic properties of IONSs. While both particle size and crystallinity exert influence over the magnetic properties of IONSs, it is apparent from the work disclosed herein that crystallinity assumes a more dominant role. This research proffers a strategic methodology for synthesizing IONPS with desired magnetic properties by finely tuning their sizes and crystallite sizes. This versatile approach holds promise for a myriad of applications, which can be broadly categorized into three distinct types:

[0143] For applications necessitating robust FiM properties, such as electronic devices, magnetic recording, and sensing, the utilization of large-sized highly crystalline IONPS with augmented FiM properties is particularly promising.

[0144] In the domains of biomedicine, biosensing, and drug delivery, large-sized SPM IONSS exhibit considerable potential, given their enhanced magnetism within the SPM regime.

[0145] Lastly, for applications requiring a moderate level of magnetism, such as magnetic separation or recoverable catalysts, the presented methodology represents a suitable tool for customizing magnetism to align with specific application requirements.

[0146] On-going works in investigating insights of nano-magnetism and discovering biomedical applications of this polycrystalline nanoparticle system have been conducted. For the future perspectives, the determination of the primary crystal size (crystallite size) at which the transition from SPM to FiM behaviors occurs, as well as insights into the magnetic behaviors of large SPM IONSs, including their nano-magnetic characteristics and inter-particle / crystal interactions, poses intriguing fundamental questions meriting further investigation.

[0147] Chapter 3

[0148] Iron oxide nanoparticles (IONPs) have been extensively used for biomedical applications due to their unique magnetic properties and biocompatibility. However, the controlled synthesis of IONPs with tunable particle sizes and crystallite / grain sizes to achieve desired magnetic functionalities between single-domain and multi-domain size ranges remains an important challenge. Here, we present a facile synthetic method capable of producing iron oxide nanospheres (IONSs) with controllable size and crystallinity for magnetic tunability. First, highly crystalline Fe3O4 IONSs (crystallite sizes above 24 nm) having an average size of 50 to 400 nm were synthesized with enhanced ferrimagnetic properties. The magnetic properties of these highly crystalline IONSs are comparable to those of their nanocube counterparts, which are generally known to possess superior magnetic properties. Second, the crystallite size can be widely tuned from 37 nm to 10 nm while maintaining the overall particle size, thereby allowing precise manipulation from the ferrimagnetic to the superparamagnetic state. In addition, demonstrations of reaction scale-up and the proposed growth mechanism of the IONSs are presented. Our study highlights the pivotal role of crystal size in controlling the magnetic properties of IONSs and offers a viable means to produce IONSs with magnetic properties desirable for wider applications in sensors, electronics, energy systems, environmental remediation, and biomedicine.

[0149] Introduction

[0150] Iron oxide nanoparticles (IONPS), such as FesCU and y-Fe2O3, have been extensively studied due to their great potential in various applications, including environmental uses, sensing technologies, wave-absorbing materials, and, notably, biomedical applications such as biosensing, magnetic hyperthermia, IR-induced phototherapy, magnetic contrast agents, and targeted drug delivery (D. Lisjak, A. Mertelj, Prog. Mater. Set. 2018, 95, 286; D. Bobo, K. J. Robinson, J. Islam, K. J. Thurecht, S. R. Corrie, Pharm. Res. 2016, 33, 2373; S. Liu, B. Yu, S. Wang, Y. Shen, H. Cong, Adv. Colloid Interface Sci. 2020, 281, 102165 ; S. Khizar, N. M. Ahmad, N. Zine, N. laffrezic-Renault, A. Errachid-el-salhi, A. Elaissari, ACS Appl. Nano Mater. 2021, 4, 4284 ; H. Gavilan, S. Kumar Avugadda, T. Femandez-Cabada, N. Soni, M. Cassani, B. T. Mai, R. Chantrell, T. Pellegrino, Chem. Soc. Rev. 2021, 50, 11614; Z. W. Tay, S. Savliwala, D. W. Hensley, K. L. B. Fung, C. Colson, B. D. Fellows, X. Zhou, Q. Huynh, Y. Lu, B. Zheng, P. Chandrasekharan, S. M. Rivera-Jimenez, C. M. Rinaldi-Ramos, S. M. Conolly, Small Methods 2021, 5, 2100796; J. Ji, Y. Huang, J. Yin, X. Zhao, X. Cheng, J. He, J. Wang, X. Li, J. Liu, J. Phys. Chem. C 2018, 122, 3628; G. C. Lavorato, R. Das, J. A. Masa, M.-H. Phan, H. Srikanth, Nanoscale Adv. 2021, 3, 867; X. Ge, J. Mohapatra, E. Silva, G. He, L. Gong, T. Lyu, R. P. Madhogaria, X. Zhao, Y. Cheng, A. M. Al-Enizi, A. Nafady, J. Tian, J. P. Liu, M.-H. Phan, F. Taraballi, R. I. Pettigrew, S. Ma, Small n.d., n / a, 2306940; P. Q. Thong, L. T. Thu Huong, N. D. Tu, H. T. My Nhung, L. Khanh, D. H. Manh, P. H. Nam, N. X. Phuc, J. Alonso, J. Qiao, S. Sridhar, H. P. Thu, M. H. Phan, N. T. Kim Thanh, Nanomedicine 2022, 17, 1677). The primary impetus driving the intensive research and discoveries is rooted in a unique combination of their properties, including environmental friendliness, cost-effectiveness, biocompatibility, half-metallicity, and diverse magnetic characteristics (M. D. Nguyen, H.-V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 11, 11301 ; H.-V. Tran, N. M. Ngo, R. Medhi, P. Srinoi, T. Liu, S. Rittikulsittichai, T. R. Lee, Materials 2022, 15, 503). To develop high-performance nanosystems based on IONPs for specific applications, the design and fabrication of highly crystalline IONPs with precise control over size, shape, and nanostructures to achieve the desired magnetic properties constitute critical steps (A. Feld, A. Weimer, A. Komowski, N. Winckelmans, J.-P. Merkl, H. Kloust, R. Zierold, C. Schmidtke, T. Schotten, M. Riedner, S. Bals, H. Weller, ACS Nano 2019, 13, 152; L. Qiao, Z. Fu, J. Li, J. Ghosen, M. Zeng, J. Stebbins, P. N. Prasad, M. T. Swihart, ACS Nano 2017, 11, 6370; X. Tian, L. Ruan, S. Zhou, L. Wu, J. Cao, X. Qi, X. Zhang, S. Shen, ACS Appl. Bio Mater. 2022, 5, 1692).Consequently, the development of synthetic methods capable of achieving such control, while ensuring a monodisperse size distribution and excellent reproducibility, remains an essential and challenging task for both fundamental and applied sciences.

[0151] With enormous potential across diverse application fields, IONPS have been synthesized in a variety of sizes and shapes, displaying a wide range of magnetic properties from superparamagnetic (SPM) to ferrimagnetic (FiM) behavior (M. D. Nguyen, H.-V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 11, 11301 ; A. Feld, A. Weimer, A. Kornowski, N. Winckelmans, J.-P. Merkl, H. Kloust, R. Zierold, C. Schmidtke, T. Schotten, M. Riedner, S. Bals, H. Weller, ACS Nano 2019, 13, 152; L. Qiao, Z. Fu, J. Li, J. Ghosen, M. Zeng, J. Stebbins, P. N. Prasad, M. T. Swihart, ACS Nano 2017, 11, 6370; J. Muro-Cruces, A. G. Roca, A. Lopez-Ortega, E. Fantechi, D. del -Pozo-Bueno, S. Estrade, F. Peiro, B. Sepulveda, F. Pineider, C. Sangregorio, J. Nogues, ACS Nano 2019, 13, 7716; M.-H. Phan, J. Alonso, H. Khurshid, P. Lampen-Kelley, S. Chandra, K. Stojak Repa, Z. Nemati, R. Das, O. Iglesias, H. Srikanth, Nanomaterials 2016, 6, 221). In addition to the challenge of synthesizing IONPs with controlled size and shape, achieving gramscale production and enhancing the reproducibility of the synthesis have been the focus of many research groups in recent years (K. M. Kirkpatrick, B. H. Zhou, P. C. Bunting, J. D. Rinehart, Chem. Mater. 2022, 34, 8043; M. Kampferbeck, L. R. Klauke, H. Weller, T. Vossmeyer, Langmuir 2021, 37, 9851; H. Gavilan, G. M. R. Rizzo, N. Silvestri, B. T. Mai, T. Pellegrino, Nat. Protoc. 2023, 1). Among the various structures of IONPs, spherical IONPs have garnered the most attention, due to ease in synthesis and isotropic magnetic properties. Synthesis has produced particles that range in size from 4 nm to even 1 pm (S. Sun, H. Zeng, J. Am. Chem. Soc. 2002, 124, 8204; J. Park, K. An, Y. Hwang, J.-G. Park, H.-J. Noh, J.-Y. Kim, J.-H. Park, N.-M. Hwang, T. Hyeon, Nat. Mater. 2004, 3, 891; H. Deng, X. Li, Q. Peng, X. Wang, J. Chen, Y. Li, Angew. Chem. Int. Ed. 2005, 44, 2782; Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152). Typically, iron oxide nanospheres (IONSS) with a diameter smaller than 25 nm exhibit a single crystal structure and possess SPM properties. Given the notable potential of SPM IONPs in biomedical applications, extensive research efforts have been directed towards advancing the control and reliability of the synthesis to achieve IONPs with desired sizes, compositions, and magnetic properties (T. Balakrishnan, M.-J. Lee, J. Dey, S.-M. Choi, CrystEngComm 2019, 21, 4063; P. K. Namaware, C. Ravikumar, J. Phys. Chem. C 2020, 124, 25010; R. Chen, M. G. Christiansen, A. Sourakov, A. Mohr, Y. Matsumoto, S. Okada, A. Jasanoff,P. Anikeeva, Nano Lett. 2016, 16, 1345; M. Unni, A. M. Uhl, S. Savliwala, B. H. Savitzky, R. Dhavalikar, N. Garraud, D. P. Arnold, L. F. Kourkoutis, J. S. Andrew, C. Rinaldi, ACS Nano 2017, 11, 2284; A. N. Solodov, J. R. Shayimova, E. A. Burilova, D. V. Shurtakova, Y. I. Zhuravleva, M. A. Cherosov, Y. Tian, A. G. Kiiamov, R. R. Amirov, J. Phys. Chem. C 2021, 125, 20980; H. Chang, B. H. Kim, H. Y. Jeong, J. H. Moon, M. Park, K. Shin, S. I. Chae, J. Lee, T. Kang, B. K. Choi, J. Yang, M. S. Bootharaju, H. Song, S. H. An, K. M. Park, J. Y. Oh, H. Lee, M. S. Kim, J. Park, T. Hyeon, J. Am. Chem. Soc. 2019, 141, 7037; I. Castellanos-Rubio, O. Arriortua, D. Iglesias-Rojas, A. Baron, I. Rodrigo, L. Marcano, J. S. Garitaonandia, I. Orue, M. L. Fdez- Gubieda, M. Insausti, Chem. Mater. 2021, 33, 8693). Therefore, the scope to further enhance the performance or properties of these small-sized IONSS (< 25 nm) depends on the design of the target applications and the strategies employed for functionalization.

[0152] On the other hand, larger IONSs (>25 nm) typically exhibit a polycrystalline structure and display a wider range of magnetic behaviors, including SPM or FiM properties (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152; S. Xuan,Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079; Y. Chen, J. Zhang,Z. Wang, Z. Zhou, Appl. Set. 2019, 9, 5157), The growth of these polycrystalline IONSs usually initiates with the formation of primary crystals, followed by the agglomeration of these primary crystals to form larger particles (S. Xuan, Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079). Consequently, their magnetic properties are primarily influenced by two structural parameters: the average diameter of the particle and the crystallite size (also referred to as 'grain size'). In here, the crystallite size represents the size of the primary crystal. Tuning these structural parameters provides an avenue to manipulate their magnetic behaviors and explore potential applications, offering an opportunity for further exploration and discovery.

[0153] In view of the developed synthesis methods, the solvothermal approach based on ethylene glycol (EG) solvent systems using iron chloride (III) precursors has proven to be the most useful, providing a facile synthetic technique to control NP size (M. D. Nguyen, H.-V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 11, 11301). Table 13, adapted from our review paper with modifications, summarizes the key results in the synthesis of IONSs using the EG solvent systembased method. IONSs synthesized via this method have been reported to exhibit either FiM or SPM properties (M. D. Nguyen, H.-V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 11, 11301). Deng et al. were the first to report this method using FeCh-6H2O precursors to synthesize FesO4 NPswith sizes of 200, 400, and 800 nm by controlling the reaction time (H. Deng, X. Li, Q. Peng, X. Wang, J. Chen, Y. Li, Angew. Chem. Int. Ed. 2005, 44, 2782). Other research groups have explored the use of a binary solvent system comprising EG and DEG to control particle size (S. Xuan, Y - X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079; S. Xuan, F. Wang, Y.- X. J. Wang, J. C. Yu, K. Cham-Fai Leung, J. Mater. Chem. 2010, 20, 5086; Y.-T. Chen, R. Medhi, I. Nekrashevich, D. Litvinov, S. Xu, T. R. Lee, Anal. Chem. 2018, 90, 6749). Leung's group also investigated the effects of sodium acetate and sodium acrylate on the size and crystallite size of IONSS (S. Xuan, Y.-X. L Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079). A study by Tong's group emphasized the significant influence of water on both the particle size and crystallite size of IONSs (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152). Despite these efforts, a precise control over the crystallinity of these nanoparticles was not achieved. In this context, we anticipate that large polycrystalline IONSs with enhanced crystallinity may exhibit stronger FiM properties.

[0154] Table 13. Synthesis and magnetic properties of polycrystalline IONSs via solvothermal method using FeCh precursors, (adapted from M. D. Nguyen, H.-V. Tran, S. Xu, T. R. E Q, Appl. Sci. 2021, 11, 11301 with modifications).

[0155] It has been shown that FiM IONSS with larger sizes yield higher saturation magnetization (Ms) (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152; Y.-T. Chen, R. Medhi, I. Nekrashevich, D. Litvinov, S. Xu, T. R. Lee, Anal. Chem. 2018, 90, 6749). However, the effects of size on the other magnetic parameters, such as coercivity (He), as listed in Table 13, are not well documented. On the other hand, crystallinity has been reported to enhance the magnetic properties of IONPS, both Ms and He (M. D. Nguyen, H.-V. Tran, S. Xu, T. R. Lee, Appl. Set. 2021, 11, 11301 ; A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, O. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010). In the case of large-sized IONSs exhibiting SPM properties, with sizes around 280 nm, an increase in grain size (crystallite size) from 5.9 to 13.5 nm, while maintaining the average size, leads to a monotonic increase in Ms from 36.2 to 67.2 emu / g (S. Xuan, Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079). Recent reports have highlighted the superior magnetic properties of Fe3O4 nanocubes compared to their nanosphere counterparts (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, O. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010; W. E. M. Elsayed, F. S. Al-Hazmi, L. S. Memesh, L. M. Bronstein, Colloids Surf. A Physicochem. Eng. Asp. 2017, 529, 239; Z. Nemati, J. Alonso, I. Rodrigo, R. Das, E. Garaio, J. A. Garcia, I. Orue, M.-H. Phan, H. Srikanth, J. Phys. Chem. C 2018, 122, 2367). Besides factorsrelated to magnetic anisotropy, crystallinity has been identified as the main determinant of the superior magnetic properties of FesCL nanocubes (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, 0. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010). Another notable study by Brougham's group, who examined two iron oxide suspensions consisting of NPs with identical size and cubic shapes, and similar dispersion quality, demonstrated significantly enhanced performance in magnetic hyperthermia and magnetic resonance imaging contrast in samples with better crystallinity and no defects (S. D. Shingte, A. H. Phakatkar, E. McKiernan, K. Nigoghossian, S. Ferguson, R. Shahbazian-Yassar, D. F. Brougham, Chem. Mater. 2022, 34, 10801). These findings underscore the critical role of improving the crystallinity of JONSs as a key approach to enhancing their magnetic properties and maximizing their potential in various applications.

[0156] Therefore, we envision that the crystallinity (crystallite / grain size) of the IONSS is the key parameter for manipulating their magnetic properties and customizing the nanoparticles for a wide range of applications. To provide a deeper understanding of the structure-to-properties relationships and to enhance the application potential of IONSs, it is crucial to develop a more refined synthetic approach with comprehensive capabilities, including: (1) producing IONSs with highly uniform size and spherical shape, (2) precisely controlling particle structure, including both size and crystallinity, (3) widely and finely tuning the magnetic properties of nanoparticles from ferrimagnetic (FiM) to superparamagnetic (SPM), and (4) achieving simplicity in technical aspects that are needed for scaling-up the reaction. To date, no synthetic approach has satisfied all these criteria to become a versatile method for preparing IONPS.

[0157] The overall aim of our research is to address the challenges mentioned above by advancing the well-established solvothermal method through controlling additives used, as illustrated in FIG. 1. We present here an efficient synthetic approach to produce highly crystalline IONSs with crystal sizes exceeding 24 nm across a broad range of size (50 to 400 nm) and to control the crystallinity of IONSs over a wide range (from 37 to 10 nm). Using NaAc AFEO combined with varying binary solvent systems, stirring speeds, and ramping rates, we successfully synthesized Fe3O4 nanospheres with sizes from 52 to 390 nm, all of which exhibit highly crystalline structures and uniform morphology. The magnetic properties of these highly crystalline IONSs are comparable to those of the single-crystalline FesO4 nanocubes of similar sizes. Wefound that while the use of trihydrate sodium acetate was instrumental in enhancing the crystallinity of the lONSs, the use of anhydrous NaAc and sodium acrylate (Na-acrylate) reduced the crystallinity. This, in turn, facilitates fine control of crystallite size over a wide range, offering a valuable means of tuning magnetic properties from the FiM to SPM state without changing particle size. This has been documented by a comprehensive study of the effects of size and crystallinity on the magnetic properties of lONSs. These important findings lead us to propose the growth mechanism of lONSs to achieve adjustable particle sizes and crystallite sizes. This work introduces an efficient synthetic approach with the capacity to fabricate lONSs of the desired size and magnetic properties, thereby serving as an indispensable tool in the design of IONP systems for applications in electronic devices, sensing technologies, and biomedicine.

[0158] Results and Discussion

[0159] Structural and Magnetic Characterization of Highly Crystalline Iron Oxide Nanospheres.

[0160] In the context of this paper, the term size refers to the “average diameter” for spherical NPs and the “average edge length” for cubic NPs. The term “crystallite size” is abbreviated as “cs”, denoting the average crystallite size, also known as the “grain size” of polycrystalline NPs. By utilizing different binary solvent systems and controlling empirical parameters such as stirring and ramping rates, highly crystalline lONSs with various sizes, from 52 to 393 nm, were successfully synthesized. FIG. 3A - FIG. 3F displays the SEM images of highly crystalline lONSs with uniform round shapes and narrow size distributions. Larger lONSs appeared to exhibit greater sphericity in their shape. In this method, vigorous stirring (at least 540 rpm) was employed, positively impacting the control of size and shape homogeneity. The slow stirring speed resulted in an extremely polydisperse size distribution of NPs, as illustrated in FIG. 13.

[0161] Powder X-ray Diffractometry (XRD) was used for phase indexing and to deduce the crystallite size of the NPs. FIG. 4 presents the X-ray diffraction patterns of highly crystalline lONSs, where strong signals with sharp peaks and high intensity indicate highly crystalline structures. The XRD patterns were matched with the ICPDS 01-088-0315 file. In all samples, clear diffraction peaks were observed at 18.35°, 30.18°, 35.55°, 37.19°, 43.21°, 53.61°, 57.15°, and 62.76°, corresponding to the lattice planes (111), (220), (311), (222), (400), (422), (511), and (440), respectively. The calculated values of the crystallite size were 30 nm, 37 nm, 26 nm, and 24nm for IONSS with average sizes of 52 ± 3, 120 ± 9, 220 ± 10, and 393 ± 27 nm, respectively. All samples exhibited a highly crystalline structure with crystallite size > 24 nm. Notably, the sample synthesized from a 15 / 25 mL EG / DEG (mL) ratio displayed the most crystalline structure. And the crystallinity reduced when more EG was used. In addition, low-intensity peaks at diffraction angles of 71.21°, 74.26°, 75.26°, and 79.24°, clearly visible in the sample synthesized from a 15 / 25 mL EG / DEG ratio were indexed for (620), (533), (622), and (444), respectively. This further confirmed the highest level of crystallinity in this sample. Despite the well-known effects of solvent mixtures on size control, no observed effects of solvent compositions on the crystallite size were noted. Our experimental results provide evidence that solvent compositions affect the crystallinity of the sample, and a 15 / 25 mL EG / DEG ratio is the optimal binary solvent ratio for forming a highly crystalline structure. Compared with other reported work (see Table 13), the IONPS presented in FIG. 3A - FIG. 3F not only exhibit highly crystalline structures with unprecedentedly large crystallite sizes (ranging from 24 to 37 nm), but also display highly uniform spherical morphologies and narrow size distributions.

[0162] The use of trihydrate sodium acetate, instead of its anhydrous version, resulted in a surprising outcome regarding the level of crystallinity. Liu et al. were the first to report the effects of water on the size and crystallite size of IONSs in solvothermal synthesis (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152). By introducing varying amounts of water into the EG solvent, the size of NPs was controlled from 80 nm to 1 pm with reported crystallite sizes ranging from 15.4 to 23.9 nm. Therefore, we hypothesized that the water content in NaAcAFEO fell within the optimal range for forming larger primary crystals. To confirm this hypothesis and investigate the effects of water on NP structure, controlled experiments with the addition of water to the synthesis were conducted, and the results are presented in Table 22. First, by replacing NaAcAFLO with anhydrous NaAc while keeping other parameters unchanged, the size of IONSs increased, but all samples had much smaller crystallite sizes (<20 nm). A series of experiments with a controlled amount of water added to the synthesis were conducted. Instead of using trihydrate chemicals, using anhydrous chemicals with 2.17 g NaAc and adding a similar amount of water to what is contained in trihydrate chemicals (1.43 mL H2O), the size and crystallite size showed almost no noticeable change. However, using less water caused an increase in the average size and a decrease in crystallite size. Further investigations by adding more water while still using NaAc 3H2O were conducted. The addition of a small amountof water, such as 180 pL, caused almost no significant changes in size and crystallite size for both solvent ratios (20 / 20 and 15 / 25). However, a larger amount of 540 pL induced noticeable changes in size and crystallinity. While adding more water consistently led to a decrease in size, the crystallite size usually increased up to a certain level before decreasing. It can be said that using a larger amount of water reduces the size, but the effect on crystallite size is not consistently monotonic. There exists a certain range of water amounts that is optimal for producing large primary crystals (crystallite size). These observations are consistent with a previous study by Tong's group, where different amounts of water were added to the synthesis using only EG solvent (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152).

[0163] To visualize the highly crystalline structure, a sample of IONSS with the largest crystallite size was characterized by Selected Area Electron Diffraction (SAED) in high-resolution TEM. Simulated Fast Fourier Transform (FFT) diffraction patterns were produced using DigitalMicrograph® software from the locations indicated by the insets. FIG. 5 provides an overview of a single crystal domain where all observable planes have a d-spacing of 0.5 nm, characteristic of the (100) plane. The difference between the theoretical (d(ioo) = 0.485 nm) and the experimental spacing is approximately 3%, which falls within the range of systematic error. The red and green insets show the exact same plane orientation, which is easily identified by observing the three diffraction patterns having the same crystal orientation. The diffraction patterns, along with XRD patterns, collectively confirmed the highly crystalline nature of the NPs.

[0164] X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy were used to confirm the phase compositions of iron oxide samples. In FIG. 23 A, the full survey spectra of highly crystalline IONSs display peaks corresponding to Fe 2p, O Is, C Is, and Fe 3p. The high- resolution Fe 2p spectra exhibit peaks at 710.4 eV and 724.1 eV, assigned to Fe 2p3 / 2 and Fe 2pi / 2, respectively (T. Yamashita, P. Hayes, Appl. Surf. Set. 2008, 254, 2441; A. P. Grosvenor, B. A. Kobe, M. C. Biesinger, N. S. McIntyre, Surf. Interface Anal. 2004, 36, 1564). The broadened features of these two peaks indicated the coexistence of Fe2+and Fe3+. A satellite peak around 718 eV is commonly observed for the y-Fe2O3 phase, which was absent in the XPS spectrum (FIG. 23A), confirming the synthesized FesO4 NPs. In addition, color of iron oxides can be used to quickly differentiate the phase purity (R. M. Cornell, U. Schwertmann, The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses, John Wiley & Sons, 2003). Highly crystalline IONSs appear entirely black, indicating the dominant presence of the magnetite (Fe3O4) phase, asshown in FIG. 23 A. The Raman spectrum (FIG. 23B), provides further confirmation of the pure magnetite phase, with a major sharp peak at -670 cm'1and minor peaks at -550 cm'1and -310 cm'1(I. Chamritski, G. Bums, J. Phys. Chem. B 2005, 109, 4965; M. Hanesch, Geophys. J. Int. 2009, 177, 941; R. Otero-Lorenzo, M. A. Ramos-Docampo, B. Rodriguez-Gonzalez, M. Comesana-Hermo, V. Salgueirino, Chem. Mater. 2017, 29, 8729).

[0165] The room -temperature magnetic properties of the synthesized IONSS were characterized using a Vibrating Sample Magnetometer (VSM). Table 14 summarizes the average size, crystallite size, and magnetic parameters (Ms, He, and Mr) of these IONSs. It can be seen in Table 14 that all the IONSs exhibit FiM behavior (non-zero values of He and Mr) at room temperature. The first observed trend is that an increase in crystallite size leads to higher He and Mr values. Samples with crystallite sizes of 24 (particle size 393 nm), 26 (particle size 220 nm), 30 (particle size 50 nm), and 37 nm (particle sizes 98 and 120 nm) exhibited increases in He (from 16 to 68 Oe) and Mr (from 3 to 20 emu / g). For samples with a similar crystalline size (37 nm) but different particle sizes (98 nm versus 120 nm), the larger particles were found to possess slightly stronger FiM properties. It is worth noting that high values of Ms (-70 emu / g) are preserved in FiM polycrystalline IONSs with particle sizes varying over a wide range of -50 to -400 nm, which are desirable for a variety of biomedical and other applications.

[0166] Table 14 Room temperature magnetic properties of poly crystalline FesO4 nanospheres with large crystallite size.

[0167] Highly Crystalline Nanospheres versus Nanocubes: A Comparative Magnetic Study.

[0168] In the realm of IONP -based biomedical applications, numerous studies have been conducted to compare the magnetic properties of spherical versus cubic IONPS (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, 0. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010; W. E. M. Elsayed, F. S. Al-Hazmi, L. S. Memesh, L. M. Bronstein, Colloids Surf. A Physicochem. Eng. Asp. 2017, 529, 239; Z. Nemati, J. Alonso, I. Rodrigo, R. Das, E. Garaio, J. A. Garcia, I. Orue, M.-H. Phan, H. Srikanth, J. Phys. Chem. C 2018, 122, 2367). It has been shown that cubic IONPs exhibit superior magnetic properties compared to their spherical counterparts (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda,A. Singh, A. C. Jamison, O. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010; Z. Nemati, R. Das, J. Alonso, E. Clements, M. H. Phan, H. Srikanth, J. Electron. Mater. 2017, 46, 3764). In our previous study, a comparative analysis of magnetic properties between these two systems revealed that the Fe3O4 nanocubes exhibited significantly higher values of Ms (1.4-3.0 times) and He (1.1-8.0 times) compared to the FesCU nanospheres (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, O. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010). To highlight the enhanced magnetism of the above-synthesized polycrystalline IONSS due to their enhanced crystalline structures and their potential applications, we have compared their FiM properties with those of single-crystalline FesCU nanocubes of similar sizes synthesized by us using the thermal decomposition method (J. Muro-Cruces, A. G. Roca, A. Lopez-Ortega, E. Fantechi, D. del-Pozo-Bueno, S. Estrade, F. Peiro,B. Sepulveda, F. Pineider, C. Sangregorio, J. Nogues, ACS Nano 2019, 13, 7716; A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, O. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010; D. Kim, N. Lee, M. Park, B. H. Kim, K. An, T. Hyeon, J. Am. Chem. Soc. 2009, 131, 454).

[0169] FIG. 7A - FIG. 7H displays TEM images of FesCh nanocubes with edge sizes varying from 43 ± 3 nm to 184 ± 23 nm. These iron oxide nanocubes were then compared with the highly crystalline IONSs of the same volume or the same body-diagonal versus diameter to matchprevious work (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C Dannangoda, A. Singh, A. C. Jamison, 0. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010). The body-diagonal and volume of the synthesized FesCU nanocubes, along with the estimates of the equivalent-volume nanospheres, were computed and are presented in Table 15. The FiM Fe3O4 nanocubes with an average size of 23 ± 4 nm were synthesized to fulfill the comprehensiveness of the study, and a corresponding TEM image is provided in FIG. 14.

[0170] The iron oxide nanocubes were characterized using high-resolution XPS spectra in the Fe 2p region, revealing peaks at 723.9 eV and 710.8 eV, corresponding to the spin-orbit split double peaks of Fe 2pi / 2 and Fe 2p3 / 2 of Fe3O4. Notably, no satellite features were observed in the 718 eV region, as shown in FIG. 16, excluding the presence of y-Fe2O3 phase (T. Yamashita, P. Hayes, Appl. Surf. Sci. 2008, 254, 2441; A. P. Grosvenor, B. A. Kobe, M. C. Biesinger, N. S. McIntyre, Surf. Interface Anal. 2004, 36, 1564). FIG. 15A - FIG. 15B shows a single crystal and its respective zoom-out view, along with SAED and HRTEM image. The high-resolution image of the nanocubes exhibits clear lattice fringes along the diagonal of cubic surface, featuring a d- spacing d(220) = 0.29 nm, which matches the value of d(220) = 0.29 nm in JCPDS 01-088-0315 file. It is also important to mention that the particle is a single crystal.

[0171] Table 15. Magnetic properties of FesCL cubic NPs with various sizes.

[0172] The effects of size on the magnetic properties of FesCh nanocubes are clearly delineated from the magnetic data summarized in Table 15. The variation in coercivity follows the transition from the single-domain and multi-domain regime, as illustrated in FIG. 17 (K. J. Klabunde, R. M. Richards, Nanoscale Materials in Chemistry, John Wiley & Sons, 2009). The He increases with size until reaching a critical size, above which the multi-domain state appears to occur, leading to a decrease in coercivity. For the presently synthesized FesCM nanocubes, He increased from 43 to 138 Oe in the size range of 23 to 82 nm, and then decreased for larger sizes. An edge length of 82 nm (corresponding to the 142-nm body-diagonal dimension) represents approximately the critical size for the FeaCh nanocubes at which a transition from the singledomain to multi-domain state occurs. It is worth noting that, while the plot illustrated in FIG. 17 is commonly used to predict the relationship between the particle size and He of a magnetic nanoparticle system, it can be adapted to describe the relationship between crystallite size and He in the polycrystalline IONSS. Regarding Ms values, it can be concluded that larger nanocubes tend to yield slightly higher Ms values. Table 15 reveals a gradual increase in Ms from 74 emu / g (size 23 nm) to approximately 79 to 82 emu / g (in the size range of 40 to 100 nm), reaching 84 emu / g for larger nanocubes (size > 120 nm). Smaller nanocubes, with their higher surface-to-volume ratio, are often known to exhibit a greater proportion of disordered / canted surface spins. Therefore, the presence of disordered / canted surface spins could result in lower Ms values in smaller nanocubes, a phenomenon commonly observed in fine magnetic nanosystems (M. D. Nguyen, H - V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 11, 11301; Z. Xu, C. Shen, Y. Hou, H. Gao, S. Sun, Chem. Mater. 2009, 21, 1778 ; A.-H. Lu, E. L. Salabas, F. Schtith, Angew. Chem. Int. Ed. 2007, 46, 1222). By analyzing the size-dependent magnetic properties of the FesCh nanocubes, we demonstrate that the relationship established (presented in FIG. 17) for the He vs. particle size dependence is generally valid for NP systems of single crystalline nature. For the polycrystalline IONSs, however, we have shown that He does not scale with particle size but with crystallite size (see Table 14). In the next part, we will discuss in detail the relation between He and crystallite size in the polycrystalline IONS system.

[0173] Now, we compare the magnetic parameters (Ms, He, and Mr) of the FesCh nanocubes to those of the FesCL nanospheres based on the same volume or the same body- diagonal(BD) / diameter (A. G. Kolhatkar, Y.-T. Chen, P. Chinwangso, I. Nekrashevich, G. C. Dannangoda, A. Singh, A. C. Jamison, 0. Zenasni, I. A. Rusakova, K. S. Martirosyan, D. Litvinov, S. Xu, R. C. Willson, T. R. Lee, ACS Omega 2017, 2, 8010). The body-diagonal of the nanocubes was chosen for this comparison because it represents the largest dimension of a cubic shape. Calculated values of BD (BD = edge length * V3) and volume (volume = (edge length)3) of the FesCU nanocubes are provided in Table 15. The nanocubes with sizes of 43, 69, 82, 101, 119, and 184 nm are estimated to have volumes equivalent to the nanospheres with sizes of 53, 86, 102, 125, 148, and 228 nm, respectively. Therefore, comparisons of similar volumes are made for the poly crystalline IONSS with average sizes of 52 ± 3, 89 ± 8, 98 ± 8, 120 ± 9, 140 ± 10, and 220 ± 10 nm. Table 16 and Table 17 present the comparative studies of the magnetic parameters of these two systems (nanocubes and nanospheres).

[0174] Table 16. Magnetic properties of FesCU cubic and spherical NPs having comparable volumes.

[0175] Table 17. Magnetic properties of FesCh cubic and spherical NPs having similar b ody-di agonal s / di ameters .

[0176] It can be seen from Table 16 and Table 17 that the values of Ms, He, and Mr for the FesC nanocubes are 1.0 to 1.15 times, 1.29 to 2.76 times, and 1.05 to 3.4 times higher than those of the FesO4 IONSS, respectively. Noticeably, the values of Ms are comparable for both systems, which once again indicates that the high crystallinity in the polycrystalline IONSs is crucial in preserving the large Ms values, suggesting that the polycrystalline IONSs are very promising for a wide range of biomedical applications. More prominent differences in He and Mr are observed in the FesO4 nanocubes compared to the FesO4 IONSs, which arise mainly from the greater contribution of both magnetocrystalline and shape anisotropies in the former (M. D. Nguyen, H - V. Tran, S. Xu, T. R. Lee, Appl. Sci. 2021, 77, 11301 ; A.-H. Lu, E. L. Salabas, F. Schiith, Angew. Chem. Int. Ed. 2007, 46, 1222).

[0177] Magnetic Tunability from Ferrimagnetism to Superparamagnetism in Iron Oxide Nanospheres: The Importance of Controlling Crystalline Sizes.

[0178] As shown above, the crystallite size of the polycrystalline IONSS plays a crucial role in determining their magnetic properties. Therefore, the ability to control crystallinity without altering the average size is crucial for fine-tuning the magnetic properties. Leung's group reported the use of sodium acrylate to adjust the crystallite size from 13.5 to 5.9 nm while maintaining an average particle size of around 280 nm (S. Xuan, Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 27, 5079). However, the magnetic properties of the IONPS were only limited to the SPM regime. It would, therefore, be important to investigate how the magnetic properties of polycrystalline IONPs vary from the FiM to SPM state when crystalline size can be tuned around a critical size. In this context, the critical size means the specific size of primary crystals (crystallite sizes) in the polycrystalline IONSs at which the transition from FiM to SPM properties occurs.

[0179] Our synthesis method has enabled us to synthesize IONSs with different crystallite sizes (10 to 37 nm) while keeping the average particle size at approximately 160 nm. FIG. 8A - FIG. 8E, for example, displays the SEM images of IONSs with a similar average size of approximately 160 nm but with varying crystallite sizes, ranging from 37, 26, 19, 12, to 10 nm. Notably, despite the wide variation in crystallite size, the uniform morphology of the nanoparticles is largely maintained. Here, samples with crystallite sizes of 37 and 26 nm, indicating a highly crystalline structure (cs > 24 nm), were synthesized using NaAc 3H2O from a solvent system containing ratios of 15 / 25 and 20 / 20 EG / DEG, respectively. By replicating the synthesis of IONSs size 160 ± 10 nm (with a cs of 26 nm), an additional amount of sodium acrylate such as 100 mg and 200 mg was introduced to reduce the cs to 19 nm and 10 nm, respectively. While the use of sodium acrylate was efficient in reducing the crystallite size, as previously reported (S. Xuan, Y - X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 27, 5079), we observed a broader size distribution and moderate deformation of the round shape. The magnetic properties of these samples were measured using the VSM. Table 18 summarizes the size, crystallite size, and magnetic properties of these IONSs. It is very interesting to note in Table 18 that the IONSs undergo a transition from the FiM (He ^0, M,-#0) to SPM (He =0, Mr=0) state, when crystalline size is reduced from 37 nm to 10 nm. For samples with crystallite sizes of 19, 26, and 37 nm, the FiM properties are achieved, with values of Ms, He, and Mr increasing with crystallite size. However, samples with crystallite sizes of 10 and 12 nm, displaying no magnetic hysteresis (Hc=0, Mr=0), exhibit a SPM-like behavior, and their Ms values are 56 and 63 emu / g, respectively. The increase in Ms values with larger crystallite sizes in these SPM IONSs is consistent with the observations of Leung’s group (S. Xuan, Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079). The critical size of the crystallite size in polycrystalline IONSs at which the FiM to SPM transition occurs, appears to be around 15 nm.

[0180] Table 18. Magnetic properties of IONSs nanospheres with same size but different crystallite sizes.

[0181] To affirm these findings, three sets of IONSS, each with a similar size around 175, 230, and 380 nm, but differing in crystallite sizes, were synthesized and characterized to check the effects of crystallinity on the magnetic (FiM vs. SPM) behaviors. FIG 10A - FIG. 10F contrasts the SEM images of these samples, with FIG.10A, FIG. 1 OB, and FIG. 10C for the highly crystalline FiM NPs (crystalline size, 26 to 34 nm), and FIG. 10D, FIG. 10E, FIG. 10F for the SPM NPs (crystallite size, 10 to 15 nm). As expected, the samples presented in FIG. 10A, FIG. 10B, FIG.IOC display obvious magnetic hysteresis (FIG. 19A), signalizing the FiM characteristic. The samples presented in FIG. 10D, FIG. 10E, FIG. 10F show no magnetic hysteresis (FIG. 19B), confirming their SPM nature at room temperature. These findings once again underscore the important role of crystallite size in controlling the nano-magnetism in magnetic nanoparticle systems.

[0182] The magnetization versus temperature measurements (M-T curves) under zero- field-cooled / field-cooled (ZFC / FC) protocol with small magnetic fields of 20 Oe were used to observe the Verwey transition (VT) (R. Das, J. Alonso, Z. Nemati Porshokouh, V. Kalappattil, D. Torres, M.-H. Phan, E. Garaio, J. A. Garcia, J. L. Sanchez Llamazares, H. Srikanth, J. Phys. Chem. C 2016, 120, 10086). This VT transition is often used to confirm the existence of pure FesCU phase and highly crystalline nature of magnetite samples (M.-H. Phan, J. Alonso, H. Khurshid, P. Lampen-Kelley, S. Chandra, K. Stojak Repa, Z. Nemati, R. Das, O. Iglesias, H. Srikanth, Nanomaterials 2016, 6, 221; R. Das, J. Alonso, Z. Nemati Porshokouh, V. Kalappattil, D. Torres, M.-H. Phan, E. Garaio, J. A. Garcia, J. L. Sanchez Llamazares, H. Srikanth, J. Phys. Chem. C 2016, 120, 10086; M. Bohra, N. Agarwal, V. Singh, J. Nanomater. 2019, 2019, e8457383). Interestingly, as shown in FIG. 24, the SPM sample with small crystallite size of ~12 nm shows a discernable VT feature at -120-130 K in the ZFC curve. In the FC curve, there is also a slight drop in magnetization within this temperature range, indicating a good match with the VT transition observed in the ZFC. VT is usually easier to observe with single-crystalline samples (R. Das, J. Alonso, Z. Nemati Porshokouh, V. Kalappattil, D. Torres, M.-H. Phan, E. Garaio, J. A. Garcia, J. L. Sanchez Llamazares, H. Srikanth, J. Phys. Chem. C 2016, 120, 10086). For the polycrystalline IONSS in our work, the observation of VT in a sample with small crystallite size indicates the predominant magnetite phase of the samples and their high crystallinity.

[0183] Superparamagnetic Properties of Size-Tunable Polycrystalline IONSs.

[0184] While it is not possible to achieve the SPM behavior in conventionally synthesized IONSs with large particle sizes (> 50 nm), our findings, as reported above, demonstrate this possibility in the presently studied polycrystalline IONSs. Indeed, we show in Table 19 that IONSs with crystallite sizes less than 15 nm (the critical SPM-size) exhibit the SPM behavior, even though their average particle size varies from 160 to 380 nm. The key to maintaining the SPM while tuning the size of NPs relies on the control of crystallite size < 15 nm. The crystallite size of 15 nm is in the single-domain SPM region. Therefore, the SPM characteristic of the large polycrystallineIONSS in the size range of a few hundred nanometers can be understood as the collective SPM behaviors of their primary crystals, whose magnetic interactions within a polycrystalline particle are less significant.

[0185] Table 19. IONSs with SPM properties in a wide range of size from 160 to 380 nm.

[0186] Despite some works reporting the SPM behavior of large IONSs, a clear understanding of the temperature-dependent magnetization associated with the SPM to FiM transition has not been established (S. Xuan, Y.-X. J. Wang, J. C. Yu, K. Cham-Fai Leung, Chem. Mater. 2009, 21, 5079; J. Ge, Y. Hu, M. Biasini, W. P. Beyermann, Y. Yin, Ange . Chem. Int. Ed. 2007, 46, 4342). Therefore, we conducted magnetization versus temperature (M-T) measurements under zero-field-cooled / field-cooled (ZFC / FC) protocol for the SPM IONSs, which are displayed in FIG. 20A - FIG. 20E. Under an applied field of 500 Oe, a large separation between the ZFC and FC magnetization curves is observed for all samples investigated. All the samples show a broadened feature of ZFC M-T curve over a measured temperature range of 2 K to 400 K, with the maxima value of ZFC below 300 K. The broadened feature of a ZFC M-T curve has been attributed to the presence of particle size distribution and inter-particle interactions (W. Xu, M. Ji, Y. Chen, H. Zheng, L. Wang, D.-L. Peng, J. Phys. Chem. C 2021, 125, 5880; R. K. Zheng, H. Gu, B. Xu, X. X. Zhang, J. Phys.: Condens. Matter 2006, 18, 5905; R. Sappey, E. Vincent, N. Hadacek, F. Chaput, J. P. Boilot, D. Zins, Phys. Rev. B 1997, 56, 14551; K. L. Livesey, S. Ruta, N. R. Anderson, D. Baldomir, R. W. Chantrell, D. Serantes, Set. Rep. 2018, 8, 11166; N. A. Frey, M. H. Phan, H. Srikanth, S. Srinath, C. Wang, S. Sun, J. Appl. Phys. 2009, 105, 07B502). In our case, clustering of primary nanocrystals forms a large particle; each particle can be considered as amulti-spin nanoclusters system. There thus exist multiple magnetic interactions in each sample, including intra- and inter-particle interactions between nanocrystals within a particle, and interactions among the particles. Effects of size distribution, including size distribution for nanocrystals that form a particle and for all particles within a sample, could also be considerable. For example, samples have similar standard deviation of about 10% of the mean value, such as large-size particles 200 ± 20 nm or small-size particles 20 ± 2 nm. Therefore, the broadening feature of the ZFC M-T curves observed for our samples (FIG. 20A - FIG. 20E) can be attributed to the size distribution of crystals and particles, as well as multiple magnetic interactions occurring within each particle and among particles.

[0187] The SPM behavior of large-sized magnetic particles is interesting and rarely reported. As discussed above, the nature of magnetic interactions, involving both intra- and interparticle interactions, creates a more complicated system than that of common single-domain SPM nanoparticles with small sizes (<25 nm). FIG. 25A - FIG. 25D provides more details of the SPM properties in a large-sized sample, showing common SPM behavior observed in other SPM nanoparticles (W. Wu, Z. Wu, T. Yu, C. Jiang, W.-S. Kim, Sci. Technol. Adv. Mater. 2015, 16, 023501; W. Wu, X. Xiao, S. Zhang, T. Peng, J. Zhou, F. Ren, C. Jiang, Nanoscale Res. Lett. 2010, 5, 1474; A. A. Krasikov, Yu. V. Knyazev, D. A. Balaev, D. A. Velikanov, S. V. Stolyar, Yu. L. Mikhlin, R. N. Yaroslavtsev, R. S. Iskhakov, Physica B Condens. Matter 2023, 660, 414901; Q. Chen, Z. J. Zhang, Appl. Phys. Lett. 1998, 73, 3156). The hysteresis loop is observed at low temperatures below the blocking temperature, as shown in FIG. 25A. The broadening feature, which arises from the size distribution of primary crystals and particle sizes (W. Xu, M. Ji, Y. Chen, H. Zheng, L. Wang, D.-L. Peng, J. Phys. Chem. C 2021, 125, 5880; R. K. Zheng, H. Gu, B. Xu, X. X. Zhang, J. Phys.: Condens. Matter 2006, 18, 5905; R. Sappey, E. Vincent, N. Hadacek, F. Chaput, J. P. Boilot, D. Zins, Phys. Rev. B 1997, 56, 14551; K. L. Livesey, S. Ruta, N. R. Anderson, D. Baldomir, R. W. Chantrell, D. Serantes, Sci. Rep. 2018, 8, 11166; N. A. Frey, M. H. Phan, H. Srikanth, S. Srinath, C. Wang, S. Sun, J. Appl. Phys. 2009, 105, 07B502), is consistently observed in the M-T curves at various applied fields (see FIG, 20D and FIG. 25B - FIG. 25D). At high fields, the VT transition might be suppressed due to the predominance of magnetic interactions. When increasing the applied field in the M-T measurements, the separation between the ZFC and FC curves narrows and eventually overlaps. The maximum magnetization region of the ZFC curve, commonly assumed to be the blocking temperature, shifts to a lower temperatureas the applied field increases (W. Wu, X. Xiao, S. Zhang, T. Peng, J. Zhou, F. Ren, C. Jiang, Nanoscale Res. Let. 2010, 5, 1474; A. A. Krasikov, Yu. V. Knyazev, D. A. Balaev, D. A. Velikanov, S. V. Stolyar, Yu. L. Mikhlin, R. N. Yaroslavtsev, R. S. Iskhakov, Physica B Condens. Mater 2023, 660, 414901; Q. Chen, Z. J. Zhang, Appl. Phys. Let. 1998, 73, 3156). These features are commonly observed in other systems of SPM nanoparticles (W. Wu, X. Xiao, S. Zhang, T. Peng, J. Zhou, F. Ren, C. Jiang, Nanoscale Res. Let. 2010, 5, 1474; A. A. Krasikov, Yu. V. Knyazev, D. A. Balaev, D. A. Velikanov, S. V. Stolyar, Yu. L. Mikhlin, R. N. Yaroslavtsev, R. S. Iskhakov, Physica B Condens. Mater 2023, 660, 414901; Q. Chen, Z. J. Zhang, Appl. Phys. Let. 1998, 73, 3156). It is worth noting that due to the close interactions of nanocrystals in polycrystalline structures, a large magnetic field is needed to observe the blocking temperature feature in the ZFC curves.

[0188] Demonstrations for the Scale-Up Synthesis of Polycrystalline IONSS.

[0189] To demonstrate the capability of method in scaling up, demonstrations with double scale-up produced highly uniform IONSs with tunable size and crystallite size were presented in FIG. 21A-FIG. 21F. The synthesis conditions and results are presented in Table 23. The synthesis at double scale was able to produce more than 0.8 g of high-quality IONSs. The first two conditions utilized sodium acetate trihydrate with solvent ratios of 15 / 25 mL and 20 / 20 mL EG / DEG perfectly replicate the result from the original scale reaction. Two samples with the size around 180 to 190 nm and crystallite sizes of 11 and 40 nm were synthesized to demonstrate the capability of tuning the crystallinity. The phase composition of IONSs synthesized under scale-up conditions were characterized by Raman spectroscopy (see FIG. 26). Highly crystalline samples synthesized with NaAc 3H2O additive exhibit a pure Fe3O4 phase (I. Chamritski, G. Burns, J. Phys. Chem. B 2005, 109, 4965; M. Hanesch, Geophys. J. Int. 2009, 177, 941; R. Otero-Lorenzo, M. A. Ramos- Docampo, B. Rodriguez-Gonzalez, M. Comesana-Hermo, V. Salgueirino, Chem. Mater. 2017, 29, 8729). The composition of the sample synthesized with an anhydrous NaAc additive, featuring small crystallite size of ~11 nm, is a mixture of FesO4 and y-FeiOs phases (I. Chamritski, G. Burns, J. Phys. Chem. B 2005, 109, 4965; M. Hanesch, Geophys. J. Int. 2009, 177, 941; R. Otero-Lorenzo, M. A. Ramos-Docampo, B. Rodriguez-Gonzalez, M. Comesana-Hermo, V. Salgueirino, Chem. Mater. 2017, 29, 8729). These results correspond well with those obtained at the original smaller reaction scale. The impact of chemical additives on particle structure and composition will be discussed in detail in section entitled “Proposed Mechanism of Growth of Polycrystalline IronOxide Nanoparticles”. The success of scaling up the reaction was achieved thanks to the effectiveness and simplicity of the method. By following the same strategy in utilizing solvent compositions, adjusting the amount of water, using different amounts of additives, and controlling experimental parameters (ramping rate, stirring speed) as described in this work, we envision that producing large-scale uniform IONSS with tunable size and crystallite size can be achieved without any forceable challenges. It is worth noting that, compared to previous works discussed in Table 13, our method is significant not only in controlling the crystallinity and size of nanoparticles for widely and finely-tuning their magnetic properties, but also in producing IONPS with narrow size distributions and uniform spherical morphologies. Moreover, the ability to scale up while maintaining uniform morphologies is highly crucial. Interestingly, all of these capabilities in producing IONPs were achieved by simply adjusting the appropriate amount of chemical additives and using a versatile pressure vessel as the reaction container.

[0190] Proposed Mechanism of Growth of Polycrystalline Iron Oxide Nanoparticles.

[0191] In this section, we discuss the proposed growth mechanism of NPs with the aim of providing guidance for optimizing the synthesis conditions to obtain iron oxide nanospheres (IONSs) with desired structures and properties. FIG. 11 illustrates the process of IONSs formation. Generally, the rate of nucleation and the growth process primarily influence the size of the primary crystals (crystallite size), while the rate at which the primary crystals agglomerate affects the overall size of the particles. Fe3+ions from FeCh precursors initially precipitate as Fe(OH)3 or FeOOH intermediates. Subsequently, the partial reduction of Fe3+within Fe(OH)3 / FeOOH converts Fe3+to Fe2+, followed by dehydration, ultimately resulting in the formation of the Fe3O4 phase. Ethylene glycol (EG) and diethylene glycol (DEG) also play crucial roles as reducing agents, possibly converting into aldehydes or carboxylic acids (J. Ji, Y. Huang, J. Yin, X. Zhao,X. Cheng, J. He, J. Wang, X. Li, J. Liu, J. Phys. Chem. C 2018, 122, 3628; Y. Liu, T. Cui, Y. Li,Y. Zhao, Y. Ye, W. Wu, G. Tong, / ter. Chem. Phys. 2016, 173, 152; Y. Wang, Y. Zheng, C. Z. Huang, Y. Xia, J. Am. Chem. Soc. 2013, 135, 1941). We will now delve into a detailed discussion of the effects of each chemical component in the synthesis process.

[0192] The effects of additives (NaAc, H2O, Na-acrylate) on phase compositions were studied by XPS, as presented in FIG. 9. Three samples synthesized using anhydrous NaAc or with the addition of sodium acrylate, were subjected to analysis. High-resolution XPS Fe 2p spectra revealed that the sample synthesized with anhydrous NaAc exhibited a satellite peak at 718.7 eV,indicating the formation of y-Fe2C>3 phase (T. Yamashita, P. Hayes, Appl. Surf. Sci. 2008, 254, 2441). Peaks at 724.1 eV and 710.3 eV were assigned to Fe 2ps / 2 and Fe 2pi / 2, respectively. We also observed a more brown or deep red-brown color of those samples synthesized with anhydrous NaAc, which suggested the presence of maghemite phase (R. M. Cornell, U. Schwertmann, The Iron Oxides: Structure, Properties, Reactions, Occurrences and Uses, John Wiley & Sons, 2003). XPS spectra consistently displayed peaks at around 724.4 eV and 710.8 eV for samples synthesized with sodium acrylate additives, without observation of obvious satellite peaks in the 718 eV region. Therefore, the use of Na-acrylate additives did not appear to influence the compositions. However, the use of anhydrous sodium acetate led to the formation of the maghemite phase. Despite the fact the co-existence of magnetite (FesCh) and maghemite (y-Fe2O3) is commonly observed, the existence of maghemite phase is a contributing factor that lowers the Ms values (M. Colombo, S. Carr egal -Romero, M. F. Casula, L. Gutierrez, M. P. Morales, I. B. Bohm, J. T. Heverhagen, D. Prosperi, W. J. Parak, Chem. Soc. Rev. 2012, 41, 4306). In general, the broadening feature of peaks at around 710 eV and 724 eV observed in all samples displayed the co-existence of Fe2+and Fe3+in samples, indicating the existence of a dominant FeiCU phase.

[0193] Water is the most critical factor in this mechanism. While an increase in the amount of water consistently led to a reduction in particle size, the crystallite size initially increased to an optimal level and subsequently decreased with further additions of water (Y. Liu, T. Cui, Y. Li, Y. Zhao, Y. Ye, W. Wu, G. Tong, Mater. Chem. Phys. 2016, 173, 152). An appropriate quantity of water effectively promoted reactions (1), (2), and (4), thereby enhancing the rate of nucleation and the growth process, resulting in the formation of larger primary crystals. However, an excess of H2O could induce the formation of complexes in reaction (6) and cause a dilution of the solvent system. This dilution, in turn, diminished the reductive capability of the solvent system (EG & DEG), thus slowing down the nucleation and growth process and resulting in a smaller crystallite size. Furthermore, H2O played a crucial role in reaction (4), facilitating the partial reduction of Fe3+to Fe2+for the formation of the magnetite phase (FeiCU). Therefore, the formation of the maghemite phasewhen using anhydrous sodium acetate can be reasonably understood.

[0194] The size of particles is primarily influenced by the rate of the agglomeration process. Nanocrystals grow until they reach a certain size range where the monomer concentration is no longer sufficient to support further growth. At this point, the nanocrystals tend to agglomerate to reduce their surface energy. The rate of agglomeration is mainly affected by the polarity andviscosity of the solvent system, which are jointly influenced by EG, DEG, and H2O. Bulky molecules with high boiling points, such as DEG, effectively slow the process, resulting in the formation of smaller particles. Similarly, a higher content of H2O typically dilutes the solution, retarding the agglomeration process and leading to the formation of smaller particles. Moreover, water molecules exhibit a greater affinity for iron cations at the surface compared to EG, DEG, and PEG molecules, owing to their higher polarity and smaller molecular size. Consequently, a relatively small change in the amount of water, on the order of a few hundred pL, can lead to a more significant alteration in particle size compared to changes in the amounts of EG and DEG (Table 22).

[0195] Sodium acetate serves as both an alkalinity controller and electrostatic stabilizer for the primary crystals. The presence of sodium acetate is essential for the formation of nanocrystals, primarily owing to its capacity to release OH' ions, which facilitate the precipitation of Fe(OH)3. In contrast, sodium acrylate contributes less to the system's alkalinity due to the relatively small quantity used (100 to 200 mg). Additionally, the acidity of acrylic acid is higher than that of acetic acid, resulting in the conjugated sodium salt being less basic. Consequently, the limited amount of sodium acrylate employed does not significantly impact the size of NPs. Furthermore, sodium acrylate can undergo polymerization to form poly(acrylate) surfactants, potentially providing greater steric hindrance for primary crystals. However, this could have a detrimental effect, leading to a broader size distribution. Nevertheless, the presence of the double bond (H2C=CH-COO(-)) in sodium acrylate may not impede the efficiency of electron transfer for reducing Fe3+to Fe2+. Therefore, the phase composition of the particles is unlikely to be affected. Diethylene glycol (DEG), apart from its role as a solvent and reducing agent, also acts as a surfactant due to structural similarities with polyethylene glycol (PEG). Thus, considering DEG as a capping agent explains the smaller particle size when a higher ratio of DEG composition is used. Considering all these complementary factors, we postulate that a balance among three components: EG, DEG, and H2O is crucial to maintaining the optimal conditions for forming larger primary crystals, thereby enhancing the crystallinity of the NPs.

[0196] Conclusions

[0197] Synthesizing IONSS with tunable sizes and degree of crystallinity over a broad range has been successfully achieved through a comprehensive synthetic approach. This approach involves the judicious use of various additives (NaAc-3H2O, H2O, NaAc anhydrous, and Na-acrylate), precise manipulation of solvent compositions (EG & DEG mixture), and meticulous adjustments to stirring speed and heating rates in the solvothermal synthesis process. Remarkably, this endeavor has resulted in the production of highly crystalline iron oxide nanospheres, accompanied by a significant enhancement in FiM properties. Notably, this advancement has effectively narrowed the gap in FiM properties between spherical and cubic geometries. Furthermore, the ability to finely control the crystallinity of these IONSS across a wide range (from 10 to 37 nm) has endowed us with a versatile tool for tailoring the magnetic properties of IONSs. While both size and crystallinity influence the magnetic properties of IONSs, it is apparent that crystallinity assumes a more dominant role. This research offers a strategic methodology for synthesizing IONPS with desired magnetic properties by finely tuning their sizes and crystallite sizes. This versatile approach holds promise for a myriad of applications, which can be broadly categorized into three distinct types:

[0198] 1. For applications requiring robust FiM properties, such as electronic devices, magnetic recording, and sensing, the utilization of large-sized highly crystalline IONPs with augmented FiM properties is particularly promising. 2. In the domains of biomedicine, biosensing, and drug delivery, large-sized SPM IONSs exhibit considerable potential, given their enhanced magnetism within the SPM regime. 3. Last, for applications requiring a moderate level of magnetism, such as magnetic separation or recoverable catalysts, the presented methodology represents a suitable tool for customizing magnetism to align with specific application requirements.

[0199] On-going works investigating insights into nano-magnetism and discovering biomedical applications of this polycrystalline nanoparticle system have been conducted. For the future perspectives, determining the primary crystal size (crystallite size) at which the transition from SPM to FiM behaviors occurs, as well as insights into the magnetic behaviors of large SPM IONSs, including their nano-magnetic characteristics and inter-particle / crystal interactions, poses intriguing fundamental questions meriting further investigation.

[0200] Various Non-Limiting Embodiments of the Invention

[0201] Embodiments include those listed below.

[0202] Embodiment 1. A magnetic nanoparticle, comprising: iron oxide, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, and wherein the magnetic nanoparticle has a crystallite size of less than or equal to 50 nm.

[0203] Embodiment 2. The magnetic nanoparticle of embodiment 1, wherein the particle size is less than 500 nm.

[0204] Embodiment 3. The magnetic nanoparticle of embodiment 1 or embodiment 2, wherein the crystallite size is less than 50 nm.

[0205] Embodiment 4. The magnetic nanoparticle of any one of embodiments 1-3, wherein the particle size is 49 nm to 420 nm.

[0206] Embodiment 5. The magnetic nanoparticle of embodiment 1, or embodiment 2, or embodiment 4, wherein the crystallite size is 5 nm to 50 nm, 10 nm to 40 nm, 24 nm to 37 nm, or 25 nm to 37 nm.

[0207] Embodiment 6. The magnetic nanoparticle of any one of embodiments 1-4, wherein the crystallite size is 5 nm to 49 nm, 10 nm to 40 nm, 24 nm to 37 nm, or 25 nm to 37 nm.

[0208] Embodiment 7. The magnetic nanoparticle of any one of embodiments 1-6, wherein the particle size is 52 nm to 393 nm, and wherein the crystallite size is 10 nm to 38 nm.

[0209] Embodiment 8. The magnetic nanoparticle of any one of embodiments 1-7, wherein the iron oxide is Fe2O3, FesCh, or combination thereof.

[0210] Embodiment 9. The magnetic nanoparticle of any one of embodiments 1-8, wherein the magnetic nanoparticle is superparamagnetic, ferrimagnetic, or combination thereof.

[0211] Embodiment 10. The magnetic nanoparticle of any one of embodiments 1-9, wherein the magnetic nanoparticle has a spherical shape.

[0212] Embodiment 11. The magnetic nanoparticle of any one of embodiments 1-10, wherein the magnetic nanoparticle is a nanosphere.

[0213] Embodiment 12. The magnetic nanoparticle of any one of embodiments 1-11, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe.

[0214] Embodiment 13. The magnetic nanoparticle of any one of embodiments 1-12, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe.

[0215] Embodiment 14. The magnetic nanoparticle of any one of embodiments 1-13, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0216] Embodiment 15. A magnetic nanoparticle, comprising: iron oxide, wherein the magnetic nanoparticle has a particle size of less than or equal to 200 nm.

[0217] Embodiment 16. The magnetic nanoparticle of embodiment 15, wherein the particle size is less than 200 nm.

[0218] Embodiment 17. The magnetic nanoparticle of embodiment 15, wherein the particle size is 20 nm to 200 nm.

[0219] Embodiment 18. The magnetic nanoparticle of any one of embodiments 15-17, wherein the particle size is 23 nm to 184 nm.

[0220] Embodiment 19. The magnetic nanoparticle of any one of embodiments 15-18, wherein the iron oxide is Fe2C>3, FesCL, or combination thereof.

[0221] Embodiment 20. The magnetic nanoparticle of any one of embodiments 15-19, wherein the magnetic nanoparticle is superparamagnetic, ferrimagnetic, or combination thereof.

[0222] Embodiment 21. The magnetic nanoparticle of any one of embodiments 15-20, wherein the magnetic nanoparticle has a polyhedral shape.

[0223] Embodiment 22. The magnetic nanoparticle of any one of embodiments 15-21, wherein the magnetic nanoparticle has a cuboid shape.

[0224] Embodiment 23. The magnetic nanoparticle of any one of embodiments 15-22, wherein the magnetic nanoparticle is a nanocube.

[0225] Embodiment 24. The magnetic nanoparticle of any one of embodiments 15-23, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe.

[0226] Embodiment 25. The magnetic nanoparticle of any one of embodiments 15-24, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe.

[0227] Embodiment 26. The magnetic nanoparticle of any one of embodiments 15-25, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0228] Embodiment 27. A method for preparing a magnetic nanoparticle, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0229] Embodiment 28. The method of embodiment 27, further comprising adding an amount of water to the second mixture.

[0230] Embodiment 29. The method of embodiment 27 or embodiment 28, further comprising adding an amount of sodium acrylate to the second mixture.

[0231] Embodiment 30. The method of any one of embodiments 27-29, further comprising adding an amount of polyethylene glycol to the second mixture.

[0232] Embodiment 31. The method of any one of embodiments 27-30, wherein the given speed of stirring is at least 250 rpm.

[0233] Embodiment 32. The method of any one of embodiments 27-30, wherein the given speed of stirring is at least 540 rpm.

[0234] Embodiment 33. The method of any one of embodiments 27-32, wherein the given rate of heating is about 4.8 °C / minute.

[0235] Embodiment 34. The method of any one of embodiments 27-32, wherein the given rate of heating is about 11 °C / minute.

[0236] Embodiment 35. The method of any one of embodiments 27-34, wherein the given ratio of ethylene glycol to diethylene glycol is 10:30, 15:25, 20:20, or 30: 10 by volume.

[0237] Embodiment 36. The method of any one of embodiments 27-35, wherein the iron(III) salt is anhydrous or hydrated.

[0238] Embodiment 37. The method of any one of embodiments 27-36, wherein the iron(III) salt is iron(III) chloride.

[0239] Embodiment 38. The method of any one of embodiments 27-37, wherein the sodium acetate is anhydrous or hydrated.

[0240] Embodiment 39. A magnetic nanoparticle made by the method of any one of embodiments 27-38.

[0241] Embodiments include those listed below.

[0242] Embodiment 40. A method of the present invention as described herein for making or preparing a magnetic nanoparticle.

[0243] Embodiment 41. A magnetic nanoparticle made by or prepared by the method of the present invention as described herein for making or preparing a magnetic nanoparticle.

[0244] Additional embodiments include those listed below.

[0245] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: iron oxide, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, and wherein the magnetic nanoparticle has a crystallite size of less than or equal to 50 nm. In some embodiments, the magnetic nanoparticle is superparamagnetic, ferrimagnetic, or combination thereof. In some embodiments, the magnetic nanoparticle has a spherical shape. In some embodiments, the magnetic nanoparticle is a nanosphere.

[0246] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: iron oxide, wherein the magnetic nanoparticle has a particle size of less than or equal to 200 nm. In some embodiments, the magnetic nanoparticle is superparamagnetic, ferrimagnetic, or combination thereof. In some embodiments, the magnetic nanoparticle has a polyhedral shape. In some embodiments, the magnetic nanoparticle has a cuboid shape. In some embodiments, the magnetic nanoparticle is a nanocube.

[0247] In various embodiments, the present invention provides a method for preparing a magnetic nanoparticle, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and di ethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate. In some embodiments, the method further comprises adding an amount of water to the first mixture and / or the second mixture. In some embodiments, the method further comprises adding an amount of water to the first mixture.In some embodiments, the method further comprises adding an amount of water to the second mixture. In some embodiments, the method further comprises adding an amount of sodium acrylate to the first mixture and / or the second mixture. In some embodiments, the method further comprises adding an amount of sodium acrylate to the first mixture. In some embodiments, the method further comprises adding an amount of sodium acrylate to the second mixture. In some embodiments, the method further comprises adding an amount of polyethylene glycol to the first mixture and / or the second mixture. In some embodiments, the method further comprises adding an amount of polyethylene glycol to the first mixture. In some embodiments, the method further comprises adding an amount of polyethylene glycol to the second mixture.

[0248] In various embodiments, the present invention provides a magnetic nanoparticle made by the method of the present invention.

[0249] Additional embodiments include those listed below.

[0250] Embodiment 42. A magnetic nanoparticle, comprising: a plurality of FesCM primary crystals, wherein the plurality of primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single FesCh crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0251] Embodiment 43. The magnetic nanoparticle of embodiment 42, wherein the magnetic nanoparticle comprises a plurality of FesCh primary crystals, wherein the plurality of primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0252] Embodiment 44. The magnetic nanoparticle of embodiment 42 or embodiment 43, wherein the particle size is 49 nm to 420 nm, and the crystallite size is 10 nm to 40 nm.

[0253] Embodiment 45. The magnetic nanoparticle of any one of embodiments 42-44, wherein the magnetic nanoparticle is a nanosphere.

[0254] Embodiment 46. The magnetic nanoparticle of any one of embodiments 42-45, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0255] Embodiment 47. The magnetic nanoparticle of any one of embodiments 42-46, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe.

[0256] Embodiment 48. The magnetic nanoparticle of any one of embodiments 42-47, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe.

[0257] Embodiment 49. The magnetic nanoparticle of any one of embodiments 42-48, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0258] Embodiment 50. The magnetic nanoparticle of embodiment 42, wherein the magnetic nanoparticle comprises a single FesCU crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0259] Embodiment 51. The magnetic nanoparticle of embodiment 42 or embodiment 50, wherein the particle size is 19 nm to 207 nm.

[0260] Embodiment 52. The magnetic nanoparticle of embodiment 42, embodiment 50, or embodiment 51, wherein the polyhedral shape is a cuboid shape.

[0261] Embodiment 53. The magnetic nanoparticle of embodiment 42, embodiment 50, embodiment 51, or embodiment 52, wherein the magnetic nanoparticle is a nanocube.

[0262] Embodiment 54. The magnetic nanoparticle of embodiment 42, embodiment 50, embodiment 51, embodiment 52, or embodiment 53, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe.

[0263] Embodiment 55. The magnetic nanoparticle of embodiment 42, embodiment 50, embodiment 51, embodiment 52, embodiment 53, or embodiment 54, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe.

[0264] Embodiment 56. The magnetic nanoparticle of embodiment 42, embodiment 50, embodiment 51, embodiment 52, embodiment 53, embodiment 54, or embodiment 55, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0265] Embodiment 57. A method for preparing a magnetic nanoparticle of embodiment 42 or embodiment 43, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0266] Embodiment 58. The method of embodiment 57, further comprising adding an amount of water to the second mixture.

[0267] Embodiment 59. The method of embodiment 57 or embodiment 58, further comprising adding an amount of sodium acrylate to the second mixture.

[0268] Embodiment 60. The method of any one of embodiments 57-59, further comprising adding an amount of polyethylene glycol to the second mixture.

[0269] Embodiment 61. A magnetic nanoparticle made by the method of any one of embodiments 57-60.

[0270] Additional embodiments include those listed below.

[0271] Embodiment 62. A magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a coreshell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0272] Embodiment 63. The magnetic nanoparticle of embodiment 62, wherein the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0273] Embodiment 64. The magnetic nanoparticle of embodiment 63, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0274] Embodiment 65. The magnetic nanoparticle of embodiment 63, wherein the iron oxide is FesCU, or Fe2Os, or combination thereof.

[0275] Embodiment 66. The magnetic nanoparticle of embodiment 63, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0276] Embodiment 67. The magnetic nanoparticle of embodiment 63, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe.

[0277] Embodiment 68. The magnetic nanoparticle of embodiment 63, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe.

[0278] Embodiment 69. The magnetic nanoparticle of embodiment 63, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0279] Embodiment 70. The magnetic nanoparticle of embodiment 62, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0280] Embodiment 71. The magnetic nanoparticle of embodiment 70, wherein the particle size is 19 nm to 207 nm.

[0281] Embodiment 72. The magnetic nanoparticle of embodiment 70, wherein the polyhedral shape is a cuboid shape.

[0282] Embodiment 73. The magnetic nanoparticle of embodiment 70, wherein the iron oxide is FesCh, or Fe2C>3, or combination thereof.

[0283] Embodiment 74. The magnetic nanoparticle of embodiment 70, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe.

[0284] Embodiment 75. The magnetic nanoparticle of embodiment 70, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe.

[0285] Embodiment 76. The magnetic nanoparticle of embodiment 70, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0286] Embodiment 77. A method for preparing a magnetic nanoparticle of embodiment 63, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0287] Embodiment 78. The method of embodiment 77, further comprising adding an amount of water to the second mixture.

[0288] Embodiment 79. The method of embodiment 77, further comprising adding an amount of sodium acrylate to the second mixture.

[0289] Embodiment 80. The method of embodiment 77, further comprising adding an amount of polyethylene glycol to the second mixture.

[0290] Embodiment 81. A magnetic nanoparticle made by the method of embodiment 77.

[0291] Embodiment 82. The method of embodiment 77, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0292] Embodiment 83. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 63, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0293] Additional embodiments include those listed below.

[0294] In some embodiments, the particle size is less than or equal to 500 nm. In some embodiments, the particle size is 49 nm, 50 nm, 51 nm, 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57 nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67 nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75 nm, 76 nm, 77 nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87 nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm, 96 nm, 97 nm, 98 nm, 99 nm, 100 nm, 101 nm, 102 nm, 103 nm, 104 nm, 105 nm, 106 nm, 107 nm,108 nm, 109 nm, 110 nm, 111 nm, 112 nm, 113 nm, 114 nm, 115 nm, 116 nm, 117 nm, 118 nm,119 nm, 120 nm, 121 nm, 122 nm, 123 nm, 124 nm, 125 nm, 126 nm, 127 nm, 128 nm, 129 nm,130 nm, 131 nm, 132 nm, 133 nm, 134 nm, 135 nm, 136 nm, 137 nm, 138 nm, 139 nm, 140 nm,141 nm, 142 nm, 143 nm, 144 nm, 145 nm, 146 nm, 147 nm, 148 nm, 149 nm, 150 nm, 151 nm,152 nm, 153 nm, 154 nm, 155 nm, 156 nm, 157 nm, 158 nm, 159 nm, 160 nm, 161 nm, 162 nm,163 nm, 164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm,nm, 175 nm, 176 nm, 177 nm, 178 nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, nm, 186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, nm, 219 nm, 220 nm, 221 nm, 222 nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, nm, 230 nm, 231 nm, 232 nm, 233 nm, 234 nm, 235 nm, 236 nm, 237 nm, 238 nm, 239 nm, nm, 241 nm, 242 nm, 243 nm, 244 nm, 245 nm, 246 nm, 247 nm, 248 nm, 249 nm, 250 nm, nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 279 nm, 280 nm, 281 nm, 282 nm, 283 nm, nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, 305 nm, nm, 307 nm, 308 nm, 309 nm, 310 nm, 311 nm, 312 nm, 313 nm, 314 nm, 315 nm, 316 nm, nm, 318 nm, 319 nm, 320 nm, 321 nm, 322 nm, 323 nm, 324 nm, 325 nm, 326 nm, 327 nm, nm, 329 nm, 330 nm, 331 nm, 332 nm, 333 nm, 334 nm, 335 nm, 336 nm, 337 nm, 338 nm, nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm, 356 nm, 357 nm, 358 nm, 359 nm, 360 nm, nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm, 368 nm, 369 nm, 370 nm, 371 nm, nm, 373 nm, 374 nm, 375 nm, 376 nm, 377 nm, 378 nm, 379 nm, 380 nm, 381 nm, 382 nm, nm, 384 nm, 385 nm, 386 nm, 387 nm, 388 nm, 389 nm, 390 nm, 391 nm, 392 nm, 393 nm, nm, 395 nm, 396 nm, 397 nm, 398 nm, 399 nm, 400 nm, 401 nm, 402 nm, 403 nm, 404 nm, nm, 406 nm, 407 nm, 408 nm, 409 nm, 410 nm, 411 nm, 412 nm, 413 nm, 414 nm, 415 nm, nm, 417 nm, 418 nm, 419 nm, 420 nm, 421 nm, 422 nm, 423 nm, 424 nm, 425 nm, 426 nm, nm, 428 nm, 429 nm, 430 nm, 431 nm, 432 nm, 433 nm, 434 nm, 435 nm, 436 nm, 437 nm, nm, 439 nm, 440 nm, 441 nm, 442 nm, 443 nm, 444 nm, 445 nm, 446 nm, 447 nm, 448 nm, nm, 450 nm, 451 nm, 452 nm, 453 nm, 454 nm, 455 nm, 456 nm, 457 nm, 458 nm, 459 nm, nm, 461 nm, 462 nm, 463 nm, 464 nm, 465 nm, 466 nm, 467 nm, 468 nm, 469 nm, 470 nm, nm, 472 nm, 473 nm, 474 nm, 475 nm, 476 nm, 477 nm, 478 nm, 479 nm, 480 nm, 481 nm, nm, 483 nm, 484 nm, 485 nm, 486 nm, 487 nm, 488 nm, 489 nm, 490 nm, 491 nm, 492 nm, nm, 494 nm, 495 nm, 496 nm, 497 nm, 498 nm, 499 nm, or 500 nm.

[0295] In some embodiments, the particle size is less than 500 nm. In some embodiments, the particle size is 150 nm, 151 nm, 152 nm, 153 nm, 154 nm, 155 nm, 156 nm, 157 nm, 158 nm,159 nm, 160 nm, 161 nm, 162 nm, 163 nm, 164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm,170 nm, 171 nm, 172 nm, 173 nm, 174 nm, 175 nm, 176 nm, 177 nm, 178 nm, 179 nm, 180 nm,181 nm, 182 nm, 183 nm, 184 nm, 185 nm, 186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm,192 nm, 193 nm, 194 nm, 195 nm, 196 nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm,203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm,214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221 nm, 222 nm, 223 nm, 224 nm,225 nm, 226 nm, 227 nm, 228 nm, 229 nm, 230 nm, 231 nm, 232 nm, 233 nm, 234 nm, 235 nm,236 nm, 237 nm, 238 nm, 239 nm, 240 nm, 241 nm, 242 nm, 243 nm, 244 nm, 245 nm, 246 nm,247 nm, 248 nm, 249 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm,258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm,269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 19 nm,280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm,291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm,302 nm, 303 nm, 304 nm, 305 nm, 306 nm, 307 nm, 308 nm, 309 nm, 310 nm, 311 nm, 312 nm,313 nm, 314 nm, 315 nm, 316 nm, 317 nm, 318 nm, 319 nm, 320 nm, 321 nm, 322 nm, 323 nm,324 nm, 325 nm, 326 nm, 327 nm, 328 nm, 329 nm, 330 nm, 331 nm, 332 nm, 333 nm, 334 nm,335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm,346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm, 356 nm,357 nm, 358 nm, 359 nm, 360 nm, 361 nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm,368 nm, 369 nm, 370 nm, 371 nm, 372 nm, 373 nm, 374 nm, 375 nm, 376 nm, 377 nm, 378 nm,379 nm, 380 nm, 381 nm, 382 nm, 383 nm, 384 nm, 385 nm, 386 nm, 387 nm, 388 nm, 389 nm,390 nm, 391 nm, 392 nm, 393 nm, 394 nm, 395 nm, 396 nm, 397 nm, 398 nm, 399 nm, 400 nm,401 nm, 402 nm, 403 nm, 404 nm, 405 nm, 406 nm, 407 nm, 408 nm, 409 nm, 410 nm, 411 nm,412 nm, 413 nm, 414 nm, 415 nm, 416 nm, 417 nm, 418 nm, 419 nm, 420 nm, 421 nm, 422 nm,423 nm, 424 nm, 425 nm, 426 nm, 427 nm, 428 nm, 429 nm, 430 nm, 431 nm, 432 nm, 433 nm,434 nm, 435 nm, 436 nm, 437 nm, 438 nm, 439 nm, 440 nm, 441 nm, 442 nm, 443 nm, 444 nm,445 nm, 446 nm, 447 nm, 448 nm, 449 nm, 450 nm, 451 nm, 452 nm, 453 nm, 454 nm, 455 nm,456 nm, 457 nm, 458 nm, 459 nm, 460 nm, 461 nm, 462 nm, 463 nm, 464 nm, 465 nm, 466 nm,467 nm, 468 nm, 469 nm, 470 nm, 471 nm, 472 nm, 473 nm, 474 nm, 475 nm, 476 nm, 477 nm,478 nm, 479 nm, 480 nm, 481 nm, 482 nm, 483 nm, 484 nm, 485 nm, 486 nm, 487 nm, 488 nm, 489 nm, 490 nm, 491 nm, 492 nm, 493 nm, 494 nm, 495 nm, 496 nm, 497 nm, 498 nm, or 499 nm.

[0296] In some embodiments, the particle size is 150 nm to 400 nm. In some embodiments, the particle size is 150 nm, 151 nm, 152 nm, 153 nm, 154 nm, 155 nm, 156 nm, 157 nm, 158 nm, 159 nm, 160 nm, 161 nm, 162 nm, 163 nm, 164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm, 174 nm, 175 nm, 176 nm, 177 nm, 178 nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, 185 nm, 186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, 196 nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221 nm, 222 nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, 229 nm, 230 nm, 231 nm, 232 nm, 233 nm, 234 nm, 235 nm, 236 nm, 237 nm, 238 nm, 239 nm, 240 nm, 241 nm, 242 nm, 243 nm, 244 nm, 245 nm, 246 nm, 247 nm, 248 nm, 249 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 279 nm, 280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, 305 nm, 306 nm, 307 nm, 308 nm, 309 nm, 310 nm, 311 nm, 312 nm, 313 nm, 314 nm, 315 nm, 316 nm, 317 nm, 318 nm, 319 nm, 320 nm, 321 nm, 322 nm, 323 nm, 324 nm, 325 nm, 326 nm, 327 nm, 328 nm, 329 nm, 330 nm, 331 nm, 332 nm, 333 nm, 334 nm, 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm, 356 nm, 357 nm, 358 nm, 359 nm, 360 nm, 361 nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm, 368 nm, 369 nm, 370 nm, 371 nm, 372 nm, 373 nm, 374 nm, 375 nm, 376 nm, 377 nm, 378 nm, 379 nm, 380 nm, 381 nm, 382 nm, 383 nm, 384 nm, 385 nm, 386 nm, 387 nm, 388 nm, 389 nm, 390 nm, 391 nm, 392 nm, 393 nm, 394 nm, 395 nm, 396 nm, 397 nm, 398 nm, 399 nm, or 400 nm.

[0297] In some embodiments, the particle size is 160 nm to 375 nm. In some embodiments, the particle size is 160 nm, 161 nm, 162 nm, 163 nm, 164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm, 174 nm, 175 nm, 176 nm, 177 nm, 178nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, 185 nm, 186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, 196 nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221 nm, 222 nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, 229 nm, 230 nm, 231 nm, 232 nm, 233 nm, 234 nm, 235 nm, 236 nm, 237 nm, 238 nm, 239 nm, 240 nm, 241 nm, 242 nm, 243 nm, 244 nm, 245 nm, 246 nm, 247 nm, 248 nm, 249 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 279 nm, 280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, 305 nm, 306 nm, 307 nm, 308 nm, 309 nm, 310 nm, 311 nm, 312 nm, 313 nm, 314 nm, 315 nm, 316 nm, 317 nm, 318 nm, 319 nm, 320 nm, 321 nm, 322 nm, 323 nm, 324 nm, 325 nm, 326 nm, 327 nm, 328 nm, 329 nm, 330 nm, 331 nm, 332 nm, 333 nm, 334 nm, 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm, 356 nm, 357 nm, 358 nm, 359 nm, 360 nm, 361 nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm, 368 nm, 369 nm, 370 nm, 371 nm, 372 nm, 373 nm, 374 nm, or 375 nm.

[0298] In some embodiments, the crystallite size is less than 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, or 14 nm.

[0299] In some embodiments, the crystallite size is 10 nm to 15 nm. In some embodiments, the crystallite size is 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm.

[0300] In some embodiments, the particle size is 49 nm to 420 nm. In some embodiments, the particle size is 49 nm, 50 nm, 51 nm, 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57 nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67 nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75 nm, 76 nm, 77 nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87 nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm, 96 nm, 97 nm, 98 nm, 99 nm, 100 nm, 101 nm, 102 nm, 103 nm, 104 nm, 105 nm, 106 nm, 107 nm, 108 nm, 109 nm, 110 nm, 111 nm, 112 nm, 113 nm, 114 nm, 115 nm, 116 nm, 117 nm, 118 nm, 119 nm, 120nm, 121 nm, 122 nm, 123 nm, 124 nm, 125 nm, 126 nm, 127 nm, 128 nm, 129 nm, 130 nm, 131 nm, 132 nm, 133 nm, 134 nm, 135 nm, 136 nm, 137 nm, 138 nm, 139 nm, 140 nm, 141 nm, 142 nm, 143 nm, 144 nm, 145 nm, 146 nm, 147 nm, 148 nm, 149 nm, 150 nm, 151 nm, 152 nm, 153 nm, 154 nm, 155 nm, 156 nm, 157 nm, 158 nm, 159 nm, 160 nm, 161 nm, 162 nm, 163 nm, 164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm, 174 nm, 175 nm, 176 nm, 177 nm, 178 nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, 185 nm, 186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, 196 nm, 197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221 nm, 222 nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, 229 nm, 230 nm, 231 nm, 232 nm, 233 nm, 234 nm, 235 nm, 236 nm, 237 nm, 238 nm, 239 nm, 240 nm, 241 nm, 242 nm, 243 nm, 244 nm, 245 nm, 246 nm, 247 nm, 248 nm, 249 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm, 255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm, 266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm, 277 nm, 278 nm, 279 nm, 280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm, 288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm, 299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, 305 nm, 306 nm, 307 nm, 308 nm, 309 nm, 310 nm, 311 nm, 312 nm, 313 nm, 314 nm, 315 nm, 316 nm, 317 nm, 318 nm, 319 nm, 320 nm, 321 nm, 322 nm, 323 nm, 324 nm, 325 nm, 326 nm, 327 nm, 328 nm, 329 nm, 330 nm, 331 nm, 332 nm, 333 nm, 334 nm, 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm, 343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm, 354 nm, 355 nm, 356 nm, 357 nm, 358 nm, 359 nm, 360 nm, 361 nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm, 368 nm, 369 nm, 370 nm, 371 nm, 372 nm, 373 nm, 374 nm, 375 nm, 376 nm, 377 nm, 378 nm, 379 nm, 380 nm, 381 nm, 382 nm, 383 nm, 384 nm, 385 nm, 386 nm, 387 nm, 388 nm, 389 nm, 390 nm, 391 nm, 392 nm, 393 nm, 394 nm, 395 nm, 396 nm, 397 nm, 398 nm, 399 nm, 400 nm, 401 nm, 402 nm, 403 nm, 404 nm, 405 nm, 406 nm, 407 nm, 408 nm, 409 nm, 410 nm, 411 nm, 412 nm, 413 nm, 414 nm, 415 nm, 416 nm, 417 nm, 418 nm, 419 nm, or 420 nm.

[0301] In some embodiments, the particle size is 52 nm to 393 nm. In some embodiments, the particle size is 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57 nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67 nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75nm, 76 nm, 77 nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87 nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm, 96 nm, 97 nm, 98 nm, 99 nm, 100 nm, 101 nm, 102 nm, 103 nm, 104 nm, 105 nm, 106 nm, 107 nm, 108 nm, 109 nm, 110 nm, 111 nm,112 nm, 113 nm, 114 nm, 115 nm, 116 nm, 117 nm, 118 nm, 119 nm, 120 nm, 121 nm, 122 nm,123 nm, 124 nm, 125 nm, 126 nm, 127 nm, 128 nm, 129 nm, 130 nm, 131 nm, 132 nm, 133 nm,134 nm, 135 nm, 136 nm, 137 nm, 138 nm, 139 nm, 140 nm, 141 nm, 142 nm, 143 nm, 144 nm,145 nm, 146 nm, 147 nm, 148 nm, 149 nm, 150 nm, 151 nm, 152 nm, 153 nm, 154 nm, 155 nm,156 nm, 157 nm, 158 nm, 159 nm, 160 nm, 161 nm, 162 nm, 163 nm, 164 nm, 165 nm, 166 nm,167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm, 174 nm, 175 nm, 176 nm, 177 nm,178 nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, 185 nm, 186 nm, 187 nm, 188 nm,189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, 196 nm, 197 nm, 198 nm, 199 nm,200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, 207 nm, 208 nm, 209 nm, 210 nm,211 nm, 212 nm, 213 nm, 214 nm, 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221 nm,222 nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, 229 nm, 230 nm, 231 nm, 232 nm,233 nm, 234 nm, 235 nm, 236 nm, 237 nm, 238 nm, 239 nm, 240 nm, 241 nm, 242 nm, 243 nm,244 nm, 245 nm, 246 nm, 247 nm, 248 nm, 249 nm, 250 nm, 251 nm, 252 nm, 253 nm, 254 nm,255 nm, 256 nm, 257 nm, 258 nm, 259 nm, 260 nm, 261 nm, 262 nm, 263 nm, 264 nm, 265 nm,266 nm, 267 nm, 268 nm, 269 nm, 270 nm, 271 nm, 272 nm, 273 nm, 274 nm, 275 nm, 276 nm,277 nm, 278 nm, 279 nm, 280 nm, 281 nm, 282 nm, 283 nm, 284 nm, 285 nm, 286 nm, 287 nm,288 nm, 289 nm, 290 nm, 291 nm, 292 nm, 293 nm, 294 nm, 295 nm, 296 nm, 297 nm, 298 nm,299 nm, 300 nm, 301 nm, 302 nm, 303 nm, 304 nm, 305 nm, 306 nm, 307 nm, 308 nm, 309 nm,310 nm, 311 nm, 312 nm, 313 nm, 314 nm, 315 nm, 316 nm, 317 nm, 318 nm, 319 nm, 320 nm,321 nm, 322 nm, 323 nm, 324 nm, 325 nm, 326 nm, 327 nm, 328 nm, 329 nm, 330 nm, 331 nm,332 nm, 333 nm, 334 nm, 335 nm, 336 nm, 337 nm, 338 nm, 339 nm, 340 nm, 341 nm, 342 nm,343 nm, 344 nm, 345 nm, 346 nm, 347 nm, 348 nm, 349 nm, 350 nm, 351 nm, 352 nm, 353 nm,354 nm, 355 nm, 356 nm, 357 nm, 358 nm, 359 nm, 360 nm, 361 nm, 362 nm, 363 nm, 364 nm,365 nm, 366 nm, 367 nm, 368 nm, 369 nm, 370 nm, 371 nm, 372 nm, 373 nm, 374 nm, 375 nm,376 nm, 377 nm, 378 nm, 379 nm, 380 nm, 381 nm, 382 nm, 383 nm, 384 nm, 385 nm, 386 nm,387 nm, 388 nm, 389 nm, 390 nm, 391 nm, 392 nm, or 393 nm.

[0302] In some embodiments, the crystallite size is less than 50 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm,16 nm, 17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37 nm, 38 nm, 39 nm, 40 nm, 41 nm, 42 nm, 43 nm, 44 nm, 45 nm, 46 nm, 47 nm, 48 nm, or 49 nm.

[0303] In some embodiments, the crystallite size is 10 nm to 40 nm. In some embodiments, the crystallite size is 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm,33 nm, 34 nm, 35 nm, 36 nm, 37 nm, 38 nm, 39 nm, or 40 nm.

[0304] In some embodiments, the crystallite size is 5 nm to 50 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37 nm, 38 nm, 39 nm, 40 nm, 41 nm, 42 nm, 43 nm, 44 nm, 45 nm, 46 nm, 47 nm, 48 nm, 49 nm, or 50 nm.

[0305] In some embodiments, the crystallite size is 24 nm to 37 nm. In some embodiments, the crystallite size is 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm,34 nm, 35 nm, 36 nm, or 37 nm.

[0306] In some embodiments, the crystallite size is 25 nm to 37 nm. In some embodiments, the crystallite size is 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm,35 nm, 36 nm, or 37 nm.

[0307] In some embodiments, the crystallite size is 10 nm to 38 nm. In some embodiments, the crystallite size is 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37 nm, or 38 nm.

[0308] In some embodiments, the magnetic saturation (Ms) value is 56 emu / g to 79 emu / g at an applied field 3000 Oe. In some embodiments, the magnetic saturation (Ms) value is 56 emu / g, 57 emu / g, 58 emu / g, 59 emu / g, 60 emu / g, 61 emu / g, 62 emu / g, 63 emu / g, 64 emu / g, 65 emu / g, 66 emu / g, 67 emu / g, 68 emu / g, 69 emu / g, 70 emu / g, 71 emu / g, 72 emu / g, 73 emu / g, 74 emu / g, 75 emu / g, 76 emu / g, 77 emu / g, 78 emu / g, or 79 emu / g.

[0309] In some embodiments, the hysteresis coercivity (HC) value is zero Oe to 135 Oe. In some embodiments, the hysteresis coercivity (HC) value is zero Oe, 1 Oe, 2 Oe, 3 Oe, 4 Oe, 5 Oe, 6 Oe, 7 Oe, 8 Oe, 9 Oe, 10 Oe, 11 Oe, 12 Oe, 13 Oe, 14 Oe, 15 Oe, 16 Oe, 17 Oe, 18 Oe, 19 Oe, 20 Oe, 21 Oe, 22 Oe, 23 Oe, 24 Oe, 25 Oe, 26 Oe, 27 Oe, 28 Oe, 29 Oe, 30 Oe, 31 Oe, 32 Oe,33 Oe, 34 Oe, 35 Oe, 36 Oe, 37 Oe, 38 Oe, 39 Oe, 40 Oe, 41 Oe, 42 Oe, 43 Oe, 44 Oe, 45 Oe, 46 Oe, 47 Oe, 48 Oe, 49 Oe, 50 Oe, 51 Oe, 52 Oe, 53 Oe, 54 Oe, 55 Oe, 56 Oe, 57 Oe, 58 Oe, 59 Oe, 60 Oe, 61 Oe, 62 Oe, 63 Oe, 64 Oe, 65 Oe, 66 Oe, 67 Oe, 68 Oe, 69 Oe, 70 Oe, 71 Oe, 72 Oe, 73 Oe, 74 Oe, 75 Oe, 76 Oe, 77 Oe, 78 Oe, 79 Oe, 80 Oe, 81 Oe, 82 Oe, 83 Oe, 84 Oe, 85 Oe, 86 Oe, 87 Oe, 88 Oe, 89 Oe, 90 Oe, 91 Oe, 92 Oe, 93 Oe, 94 Oe, 95 Oe, 96 Oe, 97 Oe, 98 Oe, 99 Oe, 100 Oe, 101 Oe, 102 Oe, 103 Oe, 104 Oe, 105 Oe, 106 Oe, 107 Oe, 108 Oe, 109 Oe, 110 Oe, 111 Oe,112 Oe, 113 Oe, 114 Oe, 115 Oe, 116 Oe, 117 Oe, 118 Oe, 119 Oe, 120 Oe, 121 Oe, 122 Oe, 123Oe, 124 Oe, 125 Oe, 126 Oe, 127 Oe, 128 Oe, 129 Oe, 130 Oe, 131 Oe, 132 Oe, 133 Oe, 134 Oe, or 135 Oe.

[0310] In some embodiments, the remnant magnetization (Mr) value is about 0 emu / g to 25 emu / g. In some embodiments, the remnant magnetization (Mr) value is about 0 emu / g, 1 emu / g, 2 emu / g, 3 emu / g, 4 emu / g, 5 emu / g, 6 emu / g, 7 emu / g, 8 emu / g, 9 emu / g, 10 emu / g, 11 emu / g, 12 emu / g, 13 emu / g, 14 emu / g, 15 emu / g, 16 emu / g, 17 emu / g, 18 emu / g, 19 emu / g, 20 emu / g, 21 emu / g, 22 emu / g, 23 emu / g, 24 emu / g, or 25 emu / g.

[0311] In some embodiments, the particle size is less than or equal to 207 nm. In some embodiments, the particle size is 19 nm to 207 nm. In some embodiments, the particle size is 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37 nm, 38 nm, 39 nm, 40 nm, 41 nm, 42 nm, 43 nm, 44 nm, 45 nm, 46 nm, 47 nm, 48 nm, 49 nm, 50 nm, 51 nm, 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57 nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67 nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75 nm, 76 nm, 77 nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87 nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm, 96 nm, 97 nm, 98 nm, 99 nm, 100 nm, 101 nm, 102 nm, 103 nm, 104 nm, 105 nm, 106 nm, 107 nm, 108 nm, 109 nm, 110 nm, 111 nm, 112 nm, 113 nm, 114 nm, 115 nm, 116 nm, 117 nm, 118 nm, 119 nm,120 nm, 121 nm, 122 nm, 123 nm, 124 nm, 125 nm, 126 nm, 127 nm, 128 nm, 129 nm, 130 nm,131 nm, 132 nm, 133 nm, 134 nm, 135 nm, 136 nm, 137 nm, 138 nm, 139 nm, 140 nm, 141 nm,142 nm, 143 nm, 144 nm, 145 nm, 146 nm, 147 nm, 148 nm, 149 nm, 150 nm, 151 nm, 152 nm,153 nm, 154 nm, 155 nm, 156 nm, 157 nm, 158 nm, 159 nm, 160 nm, 161 nm, 162 nm, 163 nm,164 nm, 165 nm, 166 nm, 167 nm, 168 nm, 169 nm, 170 nm, 171 nm, 172 nm, 173 nm, 174 nm,175 nm, 176 nm, 177 nm, 178 nm, 179 nm, 180 nm, 181 nm, 182 nm, 183 nm, 184 nm, 185 nm,186 nm, 187 nm, 188 nm, 189 nm, 190 nm, 191 nm, 192 nm, 193 nm, 194 nm, 195 nm, 196 nm,197 nm, 198 nm, 199 nm, 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm, 206 nm, or 207 nm.

[0312] In some embodiments, the magnetic saturation (Ms) value is 74 emu / g to 84 emu / g at an applied field 3000 Oe. In some embodiments, the magnetic saturation (Ms) value is 74 emu / g, 75 emu / g, 76 emu / g, 77 emu / g, 78 emu / g, 79 emu / g, 80 emu / g, 81 emu / g, 82 emu / g, 83 emu / g, or 84 emu / g at an applied field 3000 Oe.

[0313] In some embodiments, the hysteresis coercivity (HC) value is 43 Oe to 138 Oe. In some embodiments, the hysteresis coercivity (HC) value is 43 Oe, 44 Oe, 45 Oe, 46 Oe, 47 Oe, 48 Oe, 49 Oe, 50 Oe, 51 Oe, 52 Oe, 53 Oe, 54 Oe, 55 Oe, 56 Oe, 57 Oe, 58 Oe, 59 Oe, 60 Oe, 61 Oe, 62 Oe, 63 Oe, 64 Oe, 65 Oe, 66 Oe, 67 Oe, 68 Oe, 69 Oe, 70 Oe, 71 Oe, 72 Oe, 73 Oe, 74 Oe, 75 Oe, 76 Oe, 77 Oe, 78 Oe, 79 Oe, 80 Oe, 81 Oe, 82 Oe, 83 Oe, 84 Oe, 85 Oe, 86 Oe, 87 Oe, 88 Oe, 89 Oe, 90 Oe, 91 Oe, 92 Oe, 93 Oe, 94 Oe, 95 Oe, 96 Oe, 97 Oe, 98 Oe, 99 Oe, 100 Oe, 101 Oe,102 Oe, 103 Oe, 104 Oe, 105 Oe, 106 Oe, 107 Oe, 108 Oe, 109 Oe, 110 Oe, 111 Oe, 112 Oe, 113Oe, 114 Oe, 115 Oe, 116 Oe, 117 Oe, 118 Oe, 119 Oe, 120 Oe, 121 Oe, 122 Oe, 123 Oe, 124 Oe,125 Oe, 126 Oe, 127 Oe, 128 Oe, 129 Oe, 130 Oe, 131 Oe, 132 Oe, 133 Oe, 134 Oe, 135 Oe, 136Oe, 137 Oe, or 138 Oe.

[0314] In some embodiments, the remnant magnetization (Mr) value is 14 emu / g to 25 emu / g. In some embodiments, the remnant magnetization (Mr) value is 14 emu / g, 15 emu / g, 16 emu / g, 17 emu / g, 18 emu / g, 19 emu / g, 20 emu / g, 21 emu / g, 22 emu / g, 23 emu / g, 24 emu / g, or 25 emu / g.

[0315] Additional embodiments include those listed below.

[0316] In various embodiments, the magnetic nanoparticles of the present invention do not comprise FeO. In various embodiments, the magnetic nanoparticles of the present invention do not contain FeO. In various embodiments, the magnetic nanoparticles of the present invention do not consist of FeO. In various embodiments, the magnetic nanoparticles of the present invention do not consist essentially of FeO.

[0317] In various embodiments, the primary crystals of the present invention do not comprise FeO. In various embodiments, the primary crystals of the present invention do not contain FeO. In various embodiments, the primary crystals of the present invention do not consist of FeO. In various embodiments, the primary crystals of the present invention do not consist essentially of FeO.

[0318] In various embodiments, the crystallites of the present invention do not comprise FeO. In various embodiments, the crystallites of the present invention do not contain FeO. In various embodiments, the crystallites of the present invention do not consist of FeO. In various embodiments, the crystallites of the present invention do not consist essentially of FeO.

[0319] In some embodiments, the magnetic nanoparticle is not a core-shell magnetic nanoparticle. In some embodiments, the magnetic nanoparticle is not a core / shell magnetic nanoparticle. In some embodiments, the magnetic nanoparticle is not a core-shell structure. In some embodiments, the magnetic nanoparticle is not a core / shell structure. In some embodiments, the magnetic nanoparticle does not have a core-shell structure. In some embodiments, the magnetic nanoparticle does not have a core / shell structure.

[0320] In some embodiments, the iron oxide nanoparticle is not a core-shell magnetic nanoparticle. In some embodiments, the iron oxide nanoparticle is not a core-shell structure. In some embodiments, the iron oxide nanoparticle does not have a core-shell structure. In some embodiments, the iron oxide nanoparticle does not have a core / shell structure.

[0321] In some embodiments, the magnetic iron oxide nanoparticle is not a core-shell magnetic nanoparticle. In some embodiments, the magnetic iron oxide nanoparticle is not a coreshell structure. In some embodiments, the magnetic iron oxide nanoparticle does not have a coreshell structure. In some embodiments, the magnetic iron oxide nanoparticle does not have a core / shell structure.

[0322] In some embodiments, the at least one magnetic FesCU nanosphere does not have a core-shell structure. In some embodiments, the at least one magnetic FesCU nanocube does not have a core-shell structure.

[0323] In some embodiments, the FesCL nanosphere does not comprise FeO. In some embodiments, the FesO4 nanosphere does not contain FeO. In some embodiments, the FesO4 nanosphere does not consist of FeO. In some embodiments, the FesO4 nanosphere does not consist essentially of FeO. In some embodiments, the FesO4 nanosphere is not FeO.

[0324] In some embodiments, the Fe3O4 nanocube does not comprise FeO. In some embodiments, the FesO4 nanocube does not contain FeO. In some embodiments, the FesO4 nanocube does not consist of FeO. In some embodiments, the FesO4 nanocube does not consist essentially of FeO. In some embodiments, the FesO4 nanocube is not FeO.

[0325] In some embodiments, the FesCL nanocube is a magnetic FesCh nanocube. In some embodiments, the FesCh nanosphere is a magnetic FesCL nanosphere.

[0326] In some embodiments, the primary crystal does not have a core-shell structure. In some embodiments, the iron oxide primary crystal does not have a core-shell structure. In some embodiments, the crystallite does not have a core-shell structure. In some embodiments, the iron oxide crystallite does not have a core-shell structure. In some embodiments, the single iron oxide crystal does not have a core-shell structure. In some embodiments, the single crystal does not have a core-shell structure. In some embodiments, the nanosphere does not have a core-shell structure. In some embodiments, the nanocube does not have a core-shell structure.

[0327] In some embodiments, the plurality of iron oxide primary crystals does not have a core-shell structure. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not have a core-shell structure. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not comprise FeO. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not contain FeO.

[0328] In some embodiments, the at least one primary crystal does not have a core-shell structure. In some embodiments, the plurality of primary crystals does not have a core-shell structure. In some embodiments, the at least one crystallite does not have a core-shell structure. In some embodiments, the plurality of crystallites does not have a core-shell structure. In some embodiments, each of the crystallites in the plurality of crystallites does not have a core-shell structure. In some embodiments, each of the crystallites in the plurality of crystallites does not comprise FeO. In some embodiments, each of the crystallites in the plurality of crystallites does not contain FeO.

[0329] In some embodiments, the at least one iron oxide primary crystal does not have a core-shell structure. In some embodiments, the at least one iron oxide primary crystal does not comprise FeO. In some embodiments, the at least one iron oxide primary crystal does not contain FeO.

[0330] In some embodiments, the at least one crystallite does not have a core-shell structure. In some embodiments, the at least one crystallite does not comprise FeO. In some embodiments, the at least one crystallite does not contain FeO.

[0331] In some embodiments, the iron oxide is FesCL, or Fe20s, or combination thereof. In some embodiments, the iron oxide is FeaCh. In some embodiments, the iron oxide is Fe Ch. In some embodiments, the iron oxide is a combination of FeaCU and FeaCh.

[0332] In some embodiments, the iron oxide is not FeO. In some embodiments, the iron oxide does not comprise FeO. In some embodiments, the iron oxide does not contain FeO. In some embodiments, the iron oxide does not consist of FeO. In some embodiments, the iron oxide does not consist essentially of FeO.

[0333] In some embodiments, the primary crystal comprises iron oxide. In some embodiments, the crystallite comprises iron oxide. In some embodiments, the plurality of primary crystals comprise iron oxide. In some embodiments, the plurality of crystallites comprise iron oxide. In some embodiments, the at least one primary crystal comprises iron oxide. In some embodiments, the at least one crystallite comprises iron oxide.

[0334] In some embodiments, the primary crystal is an iron oxide primary crystal. In some embodiments, the plurality of primary crystals is a plurality of iron oxide primary crystals. In some embodiments, the at least one primary crystal is at least one iron oxide primary crystal.

[0335] In some embodiments, the crystallite is an iron oxide crystallite. In some embodiments, the plurality of crystallites is a plurality of iron oxide crystallites. In some embodiments, the at least one crystallite is an iron oxide crystallite.

[0336] In some embodiments, the single crystal is a single iron oxide crystal.

[0337] In some embodiments, the iron oxide nanoparticle is a magnetic iron oxide nanoparticle. In some embodiments, the magnetic nanoparticle is a magnetic iron oxide nanoparticle.

[0338] In some embodiments, the magnetic nanoparticle is a nanosphere or a nanocube. In some embodiments, the magnetic nanoparticle is a nanosphere. In some embodiments, the magnetic nanoparticle is a nanocube.

[0339] In some embodiments, the magnetic iron oxide nanoparticle is a nanosphere or a nanocube. In some embodiments, the magnetic iron oxide nanoparticle is a nanosphere. In some embodiments, the magnetic iron oxide nanoparticle is a nanocube.

[0340] In some embodiments, the iron oxide nanoparticle is a nanosphere or a nanocube. In some embodiments, the iron oxide nanoparticle is a nanosphere. In some embodiments, the iron oxide nanoparticle is a nanocube.

[0341] In some embodiments, the magnetic nanoparticle is iron oxide. In some embodiments, the magnetic nanoparticle comprises iron oxide. In some embodiments, the magnetic nanoparticle consists of iron oxide. In some embodiments, the magnetic nanoparticle consists essentially of iron oxide.

[0342] In some embodiments, the magnetic nanoparticle is FeaCh. In some embodiments, the magnetic nanoparticle comprises FeaCh. In some embodiments, the magnetic nanoparticle consists of FeaC In some embodiments, the magnetic nanoparticle consists essentially of FeaCh.

[0343] In some embodiments, the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof. In some embodiments, the magnetic nanoparticle is ferromagnetic. In some embodiments, the magnetic nanoparticle is ferrimagnetic. In some embodiments, the magnetic nanoparticle is superparamagnetic. In some embodiments, the magnetic nanoparticle is ferrimagnetic, or superparamagnetic, or combination thereof.

[0344] In some embodiments, the primary crystal is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof. In some embodiments, the primary crystal is ferromagnetic. In some embodiments, the primary crystal is ferrimagnetic. In some embodiments, the primary crystal is superparamagnetic. In some embodiments, the primary crystal is ferrimagnetic, or superparamagnetic, or combination thereof.

[0345] In some embodiments, the crystallite is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof. In some embodiments, the crystallite is ferromagnetic. In some embodiments, the crystallite is ferrimagnetic. In some embodiments, the crystallite is superparamagnetic. In some embodiments, the crystallite is ferrimagnetic, or superparamagnetic, or combination thereof.

[0346] In some embodiments, the single crystal is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof. In some embodiments, the single crystal is ferromagnetic. In some embodiments, the single crystal is ferrimagnetic. In some embodiments, the single crystal is superparamagnetic. In some embodiments, the single crystal is ferrimagnetic, or superparamagnetic, or combination thereof.

[0347] In some embodiments, the plurality of primary crystals is a plurality of iron oxide primary crystals. In some embodiments, the plurality of crystallites is a plurality of iron oxide crystallites.

[0348] In some embodiments, the at least one primary crystal is at least one iron oxide primary crystal. In some embodiments, the at least one crystallite is at least one iron oxide crystallite.

[0349] In various embodiments, the magnetic nanoparticles of the present invention do not comprise FeO. In various embodiments, the magnetic nanoparticles of the present invention do not contain FeO. In various embodiments, the magnetic nanoparticles of the present invention do not consist of FeO. In various embodiments, the magnetic nanoparticles of the present invention do not consist essentially of FeO.

[0350] In some embodiments, the magnetic nanoparticle does not comprise FeO. In some embodiments, the magnetic nanoparticle does not contain FeO. In some embodiments, the magnetic nanoparticle does not consist of FeO. In some embodiments, the magnetic nanoparticle does not consist essentially of FeO. In some embodiments, the magnetic nanoparticle is not FeO.

[0351] In some embodiments, the single iron oxide crystal does not comprise FeO. In some embodiments, the single iron oxide crystal does not contain FeO. In some embodiments, the single iron oxide crystal does not consist of FeO. In some embodiments, the single iron oxide crystal does not consist essentially of FeO. In some embodiments, the single iron oxide crystal is not FeO.

[0352] In some embodiments, the single crystal does not comprise FeO. In some embodiments, the single crystal does not contain FeO. In some embodiments, the single crystal does not consist of FeO. In some embodiments, the single crystal does not consist essentially of FeO. In some embodiments, the single crystal is not FeO.

[0353] In some embodiments, the primary crystal does not comprise FeO. In some embodiments, the primary crystal does not contain FeO. In some embodiments, the primary crystal does not consist of FeO. In some embodiments, the primary crystal does not consist essentially of FeO. In some embodiments, the primary crystal is not FeO.

[0354] In some embodiments, the plurality of primary crystals does not comprise FeO. In some embodiments, the plurality of primary crystals does not contain FeO. In some embodiments, the plurality of primary crystals does not consist of FeO. In some embodiments, the plurality of primary crystals does not consist essentially of FeO. In some embodiments, the plurality of primary crystals is not FeO.

[0355] In some embodiments, the crystallite does not comprise FeO. In some embodiments, the crystallite does not contain FeO. In some embodiments, the crystallite does not consist of FeO. In some embodiments, the crystallite does not consist essentially of FeO. In some embodiments, the crystallite is not FeO.

[0356] In some embodiments, the plurality of crystallites does not comprise FeO. In some embodiments, the plurality of crystallites does not contain FeO. In some embodiments, the plurality of crystallites does not consist of FeO. In some embodiments, the plurality of crystallites does not consist essentially of FeO. In some embodiments, the plurality of crystallites is not FeO.

[0357] In some embodiments, the magnetic nanoparticle is not a core-shell magnetic nanoparticle. In some embodiments, the magnetic nanoparticle is not a core / shell magnetic nanoparticle. In some embodiments, the magnetic nanoparticle is not a core-shell structure. In some embodiments, the magnetic nanoparticle is not a core / shell structure. In some embodiments, the magnetic nanoparticle does not have a core-shell structure. In some embodiments, the magnetic nanoparticle does not have a core / shell structure.

[0358] In some embodiments, the iron oxide primary crystal comprises FeaCU, or Fe20a, or combination thereof. In some embodiments, the iron oxide primary crystal is FeaCU, or Fe20a, or combination thereof. In some embodiments, the iron oxide primary crystal comprises FeaC In some embodiments, the iron oxide primary crystal is FeaCk In some embodiments, the iron oxide primary crystal comprises Fe20a. In some embodiments, the iron oxide primary crystal is FeaCh.

[0359] In some embodiments, the crystallite comprises FeaCk or Fe20a, or combination thereof. In some embodiments, the crystallite is FeaC or Fe2Ch, or combination thereof. In some embodiments, the crystallite comprises FeaCk In some embodiments, the crystallite is FeaCk In some embodiments, the crystallite comprises Fe C In some embodiments, the crystallite is FeaC

[0360] In some embodiments, the at least one FeaCk nanosphere further comprises FeaOa.

[0361] In some embodiments, the at least one FeaCk nanocube further comprises Fe20a.

[0362] In some embodiments, the at least one magnetic nanoparticle comprises FeaC orFeaOa, or combination thereof. In some embodiments, the at least one magnetic nanoparticle is FeaCh, or FeaOa, or combination thereof. In some embodiments, the at least one magnetic nanoparticle comprises FeaCk In some embodiments, the at least one magnetic nanoparticle isFesCk In some embodiments, the at least one magnetic nanoparticle comprises Fe20s. In some embodiments, the at least one magnetic nanoparticle is Fe20s.

[0363] In some embodiments, the magnetic nanoparticle comprises FesCL, or Fe2C>3, or combination thereof. In some embodiments, the magnetic nanoparticle is FesCU, or Fe20s, or combination thereof. In some embodiments, the magnetic nanoparticle comprises FesCk In some embodiments, the magnetic nanoparticle is Fe Ck In some embodiments, the magnetic nanoparticle comprises Fe20a. In some embodiments, the magnetic nanoparticle is Fe20a. In some embodiments, the magnetic nanoparticle further comprises FeaCk In some embodiments, the magnetic nanoparticle further comprises Fe2C

[0364] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a coreshell structure.

[0365] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0366] In various embodiments, the present invention provides a magnetic nanoparticle, comprising: a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0367] In some embodiments, the single iron oxide crystal has a polyhedral shape. In some embodiments, the single iron oxide crystal has a cuboid shape. In some embodiments, the single iron oxide crystal has a cube shape.

[0368] In some embodiments, the primary crystal has a spherical shape. In some embodiments, the crystallite has a spherical shape.

[0369] In some embodiments, the magnetic nanoparticle has a polyhedral shape. In some embodiments, the magnetic nanoparticle has a cuboid shape. In some embodiments, the magnetic nanoparticle is a nanocube.

[0370] In some embodiments, the magnetic nanoparticle has a spherical shape. In some embodiments, the magnetic nanoparticle is a nanosphere.

[0371] In some embodiments, the terms “trihydrate sodium acetate” and “sodium acetate trihydrate” have the same meaning and can be used interchangeably. In some embodiments, the terms “anhydrous sodium acetate” and “sodium acetate anhydrous” have the same meaning and can be used interchangeably.

[0372] Additional embodiments include those listed below.

[0373] In various embodiments, the present invention provides a superparamagnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the superparamagnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than or equal to 15 nm, wherein the at least one superparamagnetic nanoparticle has a spherical shape; and wherein the superparamagnetic nanoparticle does not have a core-shell structure.

[0374] In various embodiments, the present invention provides a superparamagnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the at least one superparamagnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than or equal to 15 nm, wherein the superparamagnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the superparamagnetic nanoparticle does not have a core-shell structure.

[0375] In various embodiments, the present invention provides a superparamagnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the superparamagnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallitehas a crystallite size of less than or equal to 15 nm, wherein the at least one superparamagnetic nanoparticle has a spherical shape; and wherein the superparamagnetic nanoparticle does not have a core-shell structure.

[0376] In various embodiments, the present invention provides a superparamagnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the superparamagnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than or equal to 15 nm, wherein the at least one superparamagnetic nanoparticle has a spherical shape; wherein the at least one iron oxide primary crystal does not have a core-shell structure; and wherein the superparamagnetic nanoparticle does not have a coreshell structure.

[0377] In some embodiments, the crystallite size is less than or equal to 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, or 14 nm.

[0378] In some embodiments, the crystallite size is 10 nm to 15 nm. In some embodiments, the crystallite size is 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm.

[0379] In some embodiments, the crystallite size is less than 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm. In some embodiments, the crystallite size is 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, or 14 nm.

[0380] In various embodiments, the superparamagnetic nanoparticles of the present invention do not comprise FeO. In various embodiments, the superparamagnetic nanoparticles of the present invention do not contain FeO. In various embodiments, the superparamagnetic nanoparticles of the present invention do not consist of FeO. In various embodiments, the superparamagnetic nanoparticles of the present invention do not consist essentially of FeO.

[0381] In some embodiments, the superparamagnetic nanoparticle is not a core-shell magnetic nanoparticle. In some embodiments, the superparamagnetic nanoparticle is not a core / shell magnetic nanoparticle. In some embodiments, the superparamagnetic nanoparticle is not a core-shell superparamagnetic nanoparticle. In some embodiments, the superparamagnetic nanoparticle is not a core / shell superparamagnetic nanoparticle. In some embodiments, thesuperparamagnetic nanoparticle is not a core-shell structure. In some embodiments, the superparamagnetic nanoparticle is not a core / shell structure. In some embodiments, the superparamagnetic nanoparticle does not have a core-shell structure. In some embodiments, the superparamagnetic nanoparticle does not have a core / shell structure.

[0382] In some embodiments, the superparamagnetic nanoparticle comprises FesCU, or Fe20s, or combination thereof. In some embodiments, the superparamagnetic nanoparticle is FesCh, or Fe20s, or combination thereof. In some embodiments, the superparamagnetic nanoparticle comprises FesCL. In some embodiments, the superparamagnetic nanoparticle is FesCU. In some embodiments, the superparamagnetic nanoparticle comprises Fe2O3. In some embodiments, the superparamagnetic nanoparticle is Fe2Ch. In some embodiments, the superparamagnetic nanoparticle further comprises FesCk In some embodiments, the superparamagnetic nanoparticle further comprises Fe2C>3.

[0383] In some embodiments, the superparamagnetic nanoparticle is iron oxide. In some embodiments, the superparamagnetic nanoparticle comprises iron oxide. In some embodiments, the superparamagnetic nanoparticle consists of iron oxide. In some embodiments, the superparamagnetic nanoparticle consists essentially of iron oxide.

[0384] In some embodiments, the superparamagnetic nanoparticle is FesCL. In some embodiments, the superparamagnetic nanoparticle comprises FesCh. In some embodiments, the superparamagnetic nanoparticle consists of FesCh. In some embodiments, the superparamagnetic nanoparticle consists essentially of FesCh. In some embodiments, the superparamagnetic nanoparticle further comprises Fe2O3.

[0385] In some embodiments, the superparamagnetic nanoparticle has a spherical shape. In some embodiments, the superparamagnetic nanoparticle is a nanosphere.

[0386] In some embodiments, the superparamagnetic nanoparticle does not comprise FeO. In some embodiments, the superparamagnetic nanoparticle does not contain FeO.

[0387] In some embodiments, the plurality of iron oxide primary crystals does not have a core-shell structure. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not have a core-shell structure. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not comprise FeO. In some embodiments, each of the iron oxide primary crystals in the plurality of iron oxide primary crystals does not contain FeO.

[0388] In some embodiments, the plurality of crystallites does not have a core-shell structure. In some embodiments, each of the crystallites in the plurality of crystallites does not have a core-shell structure. In some embodiments, each of the crystallites in the plurality of crystallites does not comprise FeO. In some embodiments, each of the crystallites in the plurality of crystallites does not contain FeO.

[0389] In some embodiments, the at least one iron oxide primary crystal does not have a core-shell structure. In some embodiments, the at least one iron oxide primary crystal does not comprise FeO. In some embodiments, the at least one iron oxide primary crystal does not contain FeO.

[0390] In some embodiments, the at least one crystallite does not have a core-shell structure. In some embodiments, the at least one crystallite does not comprise FeO. In some embodiments, the at least one crystallite does not contain FeO.

[0391] Additional embodiments include those listed below.

[0392] Embodiment 84. A magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a coreshell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0393] Embodiment 85. The magnetic nanoparticle of embodiment 84, wherein the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0394] Embodiment 86. The magnetic nanoparticle of embodiment 85, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0395] Embodiment 87. The magnetic nanoparticle of embodiment 85, wherein the iron oxide is FesCU, or Fe20s, or combination thereof.

[0396] Embodiment 88. The magnetic nanoparticle of embodiment 85, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0397] Embodiment 89. The magnetic nanoparticle of embodiment 85, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0398] Embodiment 90. The magnetic nanoparticle of embodiment 84, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0399] Embodiment 91. The magnetic nanoparticle of embodiment 90, wherein the particle size is 19 nm to 207 nm.

[0400] Embodiment 92. The magnetic nanoparticle of embodiment 90, wherein the polyhedral shape is a cuboid shape.

[0401] Embodiment 93. The magnetic nanoparticle of embodiment 90, wherein the iron oxide is FesCh, or Fe2Os, or combination thereof.

[0402] Embodiment 94. The magnetic nanoparticle of embodiment 90, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0403] Embodiment 95. A method for preparing a magnetic nanoparticle of embodiment 85, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0404] Embodiment 96. The method of embodiment 95, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0405] Embodiment 97. The method of embodiment 95, further comprising adding an amount of water to the second mixture.

[0406] Embodiment 98. The method of any one of embodiments 95-97, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0407] Embodiment 99. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 85, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0408] Additional embodiments include those listed below.

[0409] Embodiment 100. A magnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a coreshell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0410] Embodiment 101. The magnetic nanoparticle of embodiment 100, wherein the magnetic nanoparticle comprises at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0411] Embodiment 102. The magnetic nanoparticle of embodiment 101, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0412] Embodiment 103. The magnetic nanoparticle of embodiment 101, wherein the iron oxide is FesCh, or Fe20s, or combination thereof.

[0413] Embodiment 104. The magnetic nanoparticle of embodiment 101, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0414] Embodiment 105. The magnetic nanoparticle of embodiment 101, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0415] Embodiment 106. The magnetic nanoparticle of embodiment 100, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0416] Embodiment 107. The magnetic nanoparticle of embodiment 106, wherein the particle size is 19 nm to 207 nm.

[0417] Embodiment 108. The magnetic nanoparticle of embodiment 106, wherein the polyhedral shape is a cuboid shape.

[0418] Embodiment 109. The magnetic nanoparticle of embodiment 106, wherein the iron oxide is FesCh, or Fe20s, or combination thereof.

[0419] Embodiment 110. The magnetic nanoparticle of embodiment 106, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43Oe to 138 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0420] Embodiment 111. A method for preparing a magnetic nanoparticle of embodiment 101, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0421] Embodiment 112. The method of embodiment 111, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0422] Embodiment 113. The method of embodiment 111, further comprising adding an amount of water to the second mixture.

[0423] Embodiment 114. The method of any one of embodiment 111-113, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0424] Embodiment 115. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 101, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0425] Additional embodiments include those listed below.

[0426] Embodiment 116. A magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0427] Embodiment 117. The magnetic nanoparticle of embodiment 116, wherein the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0428] Embodiment 118. The magnetic nanoparticle of embodiment 117, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0429] Embodiment 119. The magnetic nanoparticle of embodiment 117, wherein the iron oxide is FesCh, or FeiCh, or combination thereof.

[0430] Embodiment 120. The magnetic nanoparticle of embodiment 117, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0431] Embodiment 121. The magnetic nanoparticle of embodiment 117, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe.

[0432] Embodiment 122. The magnetic nanoparticle of embodiment 117, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe.

[0433] Embodiment 123. The magnetic nanoparticle of embodiment 117, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0434] Embodiment 124. The magnetic nanoparticle of embodiment 116, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0435] Embodiment 125. The magnetic nanoparticle of embodiment 124, wherein the particle size is 19 nm to 207 nm.

[0436] Embodiment 126. The magnetic nanoparticle of embodiment 124, wherein the polyhedral shape is a cuboid shape.

[0437] Embodiment 127. The magnetic nanoparticle of embodiment 124, wherein the iron oxide is FesCh, or Fe2Os, or combination thereof.

[0438] Embodiment 128. The magnetic nanoparticle of embodiment 124, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe.

[0439] Embodiment 129. The magnetic nanoparticle of embodiment 124, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe.

[0440] Embodiment 130. The magnetic nanoparticle of embodiment 124, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0441] Embodiment 131. A method for preparing a magnetic nanoparticle of embodiment117, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0442] Embodiment 132. The method of embodiment 131, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0443] Embodiment 133. The method of embodiment 131, further comprising adding an amount of water to the second mixture.

[0444] Embodiment 134. The method of any one of embodiment 131, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0445] Embodiment 135. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 117, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0446] Additional embodiments include those listed below.

[0447] Embodiment 136. A magnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the at least one iron oxide primary crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0448] Embodiment 137. The magnetic nanoparticle of embodiment 136, wherein the magnetic nanoparticle comprises at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the at least one iron oxide primary crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0449] Embodiment 138. The magnetic nanoparticle of embodiment 137, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0450] Embodiment 139. The magnetic nanoparticle of embodiment 137, wherein the iron oxide is FesCh, or Fe20s, or combination thereof.

[0451] Embodiment 140. The magnetic nanoparticle of embodiment 137, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0452] Embodiment 141. The magnetic nanoparticle of embodiment 137, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe.

[0453] Embodiment 142. The magnetic nanoparticle of embodiment 137, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe.

[0454] Embodiment 143. The magnetic nanoparticle of embodiment 137, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0455] Embodiment 144. The magnetic nanoparticle of embodiment 136, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0456] Embodiment 145. The magnetic nanoparticle of embodiment 144, wherein the particle size is 19 nm to 207 nm.

[0457] Embodiment 146. The magnetic nanoparticle of embodiment 144, wherein the polyhedral shape is a cuboid shape.

[0458] Embodiment 147. The magnetic nanoparticle of embodiment 144, wherein the iron oxide is FesCM, or Fe20s, or combination thereof

[0459] Embodiment 148. The magnetic nanoparticle of embodiment 144, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe.

[0460] Embodiment 149. The magnetic nanoparticle of embodiment 144, wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe.

[0461] Embodiment 150. The magnetic nanoparticle of embodiment 144, wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0462] Embodiment 151. A method for preparing a magnetic nanoparticle of embodiment 137, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0463] Embodiment 152. The method of embodiment 151, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0464] Embodiment 153. The method of embodiment 151, further comprising adding an amount of water to the second mixture.

[0465] Embodiment 154. The method of embodiment 151, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0466] Embodiment 155. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 137, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodiumacetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0467] Additional embodiments include those listed below.

[0468] Embodiment 156. A magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0469] Embodiment 157. The magnetic nanoparticle of embodiment 156, wherein the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0470] Embodiment 158. The magnetic nanoparticle of embodiment 157, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0471] Embodiment 159. The magnetic nanoparticle of embodiment 157, wherein the iron oxide is FesCh, or Fe20s, or combination thereof.

[0472] Embodiment 160. The magnetic nanoparticle of embodiment 157, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0473] Embodiment 161. The magnetic nanoparticle of embodiment 157, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0474] Embodiment 162. The magnetic nanoparticle of embodiment 156, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0475] Embodiment 163. The magnetic nanoparticle of embodiment 162, wherein the particle size is 19 nm to 207 nm.

[0476] Embodiment 164. The magnetic nanoparticle of embodiment 162, wherein the polyhedral shape is a cuboid shape.

[0477] Embodiment 165. The magnetic nanoparticle of embodiment 162, wherein the iron oxide is FesCM, or Fe20s, or combination thereof.

[0478] Embodiment 166. The magnetic nanoparticle of embodiment 162, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

[0479] Embodiment 167. A method for preparing a magnetic nanoparticle of embodiment 157, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture; stirring the second mixture at a given speed; and heating the second mixture at a given rate.

[0480] Embodiment 168. The method of embodiment 167, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

[0481] Embodiment 169. The method of embodiment 167, further comprising adding an amount of water to the second mixture.

[0482] Embodiment 170. The method of any one of embodiments 167-169, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

[0483] Embodiment 171. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of embodiment 157, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; and wherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

[0484] Additional embodiments include those listed below.

[0485] Embodiment 172. A magnetic nanoparticle, comprising: at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the at least one iron oxide primary crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size ofless than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0486] Embodiment 173. The magnetic nanoparticle of embodiment 172, wherein the magnetic nanoparticle comprises at least one iron oxide primary crystal, wherein the at least one iron oxide primary crystal comprises at least one crystallite, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the at least one crystallite has a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the at least one iron oxide primary crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

[0487] Embodiment 174. The magnetic nanoparticle of embodiment 173, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

[0488] Embodiment 175. The magnetic nanoparticle of embodiment 173, wherein the iron oxide is FesCU, or Fe2Os, or combination thereof.

[0489] Embodiment 176. The magnetic nanoparticle of embodiment 173, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof.

[0490] Embodiment 177. The magnetic nanoparticle of embodiment 173, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

[0491] Embodiment 178. The magnetic nanoparticle of embodiment 172, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structu...

Claims

CLAIMSWhat is claimed is:

1. A magnetic nanoparticle, comprising: a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure; or a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

2. The magnetic nanoparticle of claim 1, wherein the magnetic nanoparticle comprises a plurality of iron oxide primary crystals, wherein the plurality of iron oxide primary crystals comprise a plurality of crystallites, wherein the magnetic nanoparticle has a particle size of less than or equal to 500 nm, wherein the plurality of crystallites have a crystallite size of less than 50 nm, wherein the magnetic nanoparticle has a spherical shape; wherein the plurality of iron oxide primary crystals does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

3. The magnetic nanoparticle of claim 2, wherein the particle size is 49 nm to 420 nm, and wherein the crystallite size is 10 nm to 40 nm.

4. The magnetic nanoparticle of claim 2, wherein the iron oxide is FesC , or Fe2C>3, or combination thereof.

5. The magnetic nanoparticle of claim 2, wherein the magnetic nanoparticle is ferromagnetic, ferrimagnetic, or superparamagnetic, or any combination thereof6. The magnetic nanoparticle of claim 2, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 56 emu / g to 79 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of zero Oe to 135 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of about 0 emu / g to 25 emu / g.

7. The magnetic nanoparticle of claim 1, wherein the magnetic nanoparticle comprises a single iron oxide crystal, wherein the magnetic nanoparticle has a particle size of less than or equal to 207 nm, wherein the magnetic nanoparticle has a polyhedral shape; wherein the single iron oxide crystal does not have a core-shell structure; and wherein the magnetic nanoparticle does not have a core-shell structure.

8. The magnetic nanoparticle of claim 7, wherein the particle size is 19 nm to 207 nm.

9. The magnetic nanoparticle of claim 7, wherein the polyhedral shape is a cuboid shape.

10. The magnetic nanoparticle of claim 7, wherein the iron oxide is FesCh, or Fe2Os, or combination thereof.

11. The magnetic nanoparticle of claim 7, wherein the magnetic nanoparticle has a magnetic saturation (Ms) value of 74 emu / g to 84 emu / g at an applied field 3000 Oe; or wherein the magnetic nanoparticle has a hysteresis coercivity (He) value of 43 Oe to 138 Oe; or wherein the magnetic nanoparticle has a remnant magnetization (Mr) value of 14 emu / g to 25 emu / g.

12. A method for preparing a magnetic nanoparticle of claim 2, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt;combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, stirring the second mixture at a given speed; and heating the second mixture at a given rate.

13. The method of claim 12, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous.

14. The method of claim 12, further comprising adding an amount of water to the second mixture.

15. The method of any one of claims 12-14, further comprising adding an amount of sodium acrylate to the second mixture, and optionally further comprising adding an amount of polyethylene glycol to the second mixture.

16. A method for adjusting the crystallite size and magnetic behavior of a magnetic nanoparticle of claim 2, the method comprising: providing a solvent, wherein the solvent comprises ethylene glycol and diethylene glycol at a given ratio; providing an iron(III) salt; combining the iron(III) salt and the solvent to form a first mixture; adding an amount of sodium acetate to the first mixture to form a second mixture, wherein the sodium acetate is sodium acetate trihydrate or sodium acetate anhydrous; stirring the second mixture at a given speed; and heating the second mixture at a given rate; wherein if the sodium acetate is sodium acetate trihydrate the crystallite size of the magnetic nanoparticle is enlarged relative to if the sodium acetate is sodium acetate anhydrous, and the magnetic nanoparticle produced using sodium acetate trihydrate exhibits an increase in ferrimagnetic behavior and a decrease in superparamagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate anhydrous; andwherein if the sodium acetate is sodium acetate anhydrous the crystallite size of the magnetic nanoparticle is reduced relative to if the sodium acetate is sodium acetate trihydrate, and the magnetic nanoparticle produced using sodium acetate anhydrous exhibits an increase in superparamagnetic behavior and a decrease in ferrimagnetic behavior relative to the magnetic nanoparticle produced using sodium acetate trihydrate.

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