Patent Application
20200317522
Exemplary embodiments of the invention relate generally to a flow synthesis system (FSS) based on contamination free PTFE tubing, a pump for pumping requisite solutions, and a heater for heating precipitated flow suspensions for the synthesis of inorganic particles in near ambient conditions.
Traditional approaches for the synthesis of bioceramics depend on materials which require strict parameters control or very long synthesis periods. The majority of room temperature batch synthesis methods for bioceramics tend to be multi-step, energy intensive, or time consuming processes. For example, in wet chemical syntheses of hydroxyapatite (HA), a maturation step (>18 h), followed by a heat treatment of 650° C., is required. Although batch hydrothermal process facilitates a simpler, lower temperature based and relatively efficient way to synthesize phase pure HA however, most of the time it requires templating agents along with long reaction time (up to 24 hours).
Current continuous production of HA is carried out at temperatures in excess of the range of 200-400° C., which is energy intensive. Furthermore, at such high temperatures, although nucleation occurs, there is substantial growth or agglomeration of smaller nuclei to form substantially larger particles. Additionally, there is a disadvantage of having to use high temperature continuous systems, in that they are conducted in an all metal tubing setup—due to the high reaction temperatures. Therefore, if such a process were used to make bioceramics, they would contain substantial levels of leached metals from the steel (e.g. Fe, Cr, etc.). This would mean that the bioceramics may not be acceptable for clinical use based on unwanted metal ions present. Consequently, a need arises to develop smaller nano-sized calcium phosphates using methods, which allow for fine control over particle sizes, preferably under relatively mild conditions of temperature and pressure, and with purity acceptable for use in a clinical setting such as for bone replacement. One known method of HA production at near ambient conditions (20-60° C.) was reported in the patent literature that involves the mixing of reagents in multiple stages using a multiple step reactor with strong stirring.
Similarly, for oxides much work has been published on ZnO and ZnO doped materials' synthesis routes and applications. However, a simple and quick route that provides access to nanosized particles with tailorable properties is highly desirable. Phase pure and doped zinc oxides are generally synthesized via wet-chemical/precipitation, sol-gel methods, co-precipitation, solid-thermal methods, hydrothermal synthesis, emulsion techniques, and spray pyrolysis. Flow synthesis of ZnO is a relatively new approach. Reports in literature rely on complex and expensive flow systems which rely on high temperature and pressure. Therefore, there is a need for a simple flow methodology which facilitates a one-step, rapid route to synthesis.
Therefore, attempts have been made to develop a simple, low cost, clean, synthesis technique, which could work under mild conditions and allow the synthesis of high purity stoichiometric HA and other bioceramic materials in a considerably short time period with a fine and controllable particle size (range from 20-150 nm) and controlled surface area (typically range from 95-300 m2g−1), depending on reaction conditions.
The above information disclosed in this Background section is only for understanding of the background of the inventive concepts, and, therefore, it may contain information that does not constitute prior art.
Devices constructed according to exemplary implementations and methods according to exemplary embodiments of the invention are capable of synthesis of inorganic particles in near ambient conditions.
A flow synthesis system (FSS) based on contamination free PTFE tubing, a pump for pumping requisite solutions and a heater for heating precipitated flow suspensions has been designed. This novel design is based on the need to develop calcium phosphate and oxide based nanoceramics with tailorable properties in a simple single step synthesis method. Synthesis therefore, using FSS, eliminates the need for secondary heat-treatments and/or long ageing times required in traditional inorganic synthesis routes. The FSS was used successfully to synthesis calcium phosphates which include phase-pure and ion substituted hydroxyapatite, respectively. Biologically beneficial Magnesium, Zinc, Carbonate and Silicon ions were successfully incorporated into hydroxyapatite. The versatility of FSS to synthesis calcium phosphates based on different precursors was also elucidated in this work. These nanoparticles can have great range of applications for use in replacement of hard tissues such as bone and teeth, as bone graft substitutes, injectable solutions, coatings on metallic implants, as fillers or additives in commercial products, such as toothpastes; materials for the controlled release of drugs, or other controlled release therapies; reinforcements in biomedical composites, and in bone and dental cements. The novel FSS was also used to synthesize phase-pure oxides which include ZnO and CeO2. Doped zinc oxides were also obtained by successfully incorporation of K, Fe, Ca, Ce & Mg ions in zinc oxide whilst retaining the original phase (proven through extensive X-ray Diffraction Studies). These compositional directives influence particulate properties which include size and morphology. Promising photocatalysts, antibacterial agents (standalone or as reinforcements in polymers) and semiconductors were hence synthesized based on sizeable reduction in band gaps as a result of doping. Summarily, novel FSS developed herein is the first instance of its kind. Its use therefore to synthesize materials for bone regeneration, photo catalysis, antibacterial response and semiconducting applications is carefully elucidated.
Additional features of the inventive concepts will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the inventive concepts.
In an exemplary embodiment of the invention, a system includes: a pump with three feeds; a stainless steel T-piece reactor; and a heater having tubing passing through it. The pump is connected to the T-piece reactor, the T-piece reactor is connected to the tubing passing through the heater, and the feeds and the tubing are formed of contamination free polytetrafluoroethylene (PTFE).
A first feed of the pump may send a first solution to the T-piece reactor and a second feed of the pump may send a second solution to the T-piece reactor.
The third feed of the pump may send a third solution to the T-piece reactor.
The exemplary system may be used in a method to synthesize inorganic particles, wherein the solutions from at least two feeds of the pump react in the T-piece reactor to form a reaction suspension.
The reaction suspension of the T-piece reactor may pass through the heater.
The suspension may exit from the heater and be collected in a container in a continuous manner.
The first solution and second solution may be selected for continuous flow synthesis of grafted and non-grafted inorganic nanoparticles.
The first solution and second solution may be selected for the synthesis of inorganic particles and nanoparticles.
The first solution and second solution may be selected for the synthesis of inorganic particles and nanoparticles of a single phase.
The first solution and second solution may be selected for the synthesis of inorganic particles and nanoparticles belonging to different phases.
The first solution and second solution may be selected for the synthesis of inorganic particles and nanoparticles grafted with organic groups.
The first solution and second solution may be selected for synthesis based on variable flow rates.
The pump may maintain the same flow rate in all feeds.
The reaction times may be varied based on flow rates.
The reactions times may be increased by increasing a length of the tubing in the heater.
Different solution concentrations may be used to influence reaction yield.
A pH of the feed solutions may be varied.
A pH of all feed solutions may be varied independently.
The inorganic particles may be synthesized with varying crystallinity.
The reaction temperatures may be varied.
The reaction temperatures may be varied to influence phase purity of product.
The reaction temperatures may be varied to influence crystallinity.
Grafted and non-grafted inorganic particles and nanoparticles may be synthesized in gram and kilogram level yields.
Different elements may be doped into inorganic particles and nanoparticles.
The resultant particle size may be varied.
The dopant levels into inorganic particles and nanoparticles may be varied.
The reactions may be carried out based on a water soluble reagent.
The feeds may be in the form of suspensions.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention, and together with the description serve to explain the inventive concepts.
In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of various exemplary embodiments or implementations of the invention. As used herein “embodiments” and “implementations” are interchangeable words that are non-limiting examples of devices or methods employing one or more of the inventive concepts disclosed herein. It is apparent, however, that various exemplary embodiments may be practiced without these specific details or with one or more equivalent arrangements. In other instances, well-known structures and devices are shown in block diagram form in order to avoid unnecessarily obscuring various exemplary embodiments. Further, various exemplary embodiments may be different, but do not have to be exclusive. For example, specific shapes, configurations, and characteristics of an exemplary embodiment may be used or implemented in another exemplary embodiment without departing from the inventive concepts.
Unless otherwise specified, the illustrated exemplary embodiments are to be understood as providing exemplary features of varying detail of some ways in which the inventive concepts may be implemented in practice. Therefore, unless otherwise specified, the features, components, modules, layers, films, panels, regions, and/or aspects, etc. (hereinafter individually or collectively referred to as “elements”), of the various embodiments may be otherwise combined, separated, interchanged, and/or rearranged without departing from the inventive concepts.
When an element is referred to as being “on,” “connected to,” or “coupled to” another element, it may be directly on, connected to, or coupled to the other element or intervening elements may be present. When, however, an element is referred to as being “directly on,” “directly connected to,” or “directly coupled to” another element, there are no intervening elements present. To this end, the term “connected” may refer to physical, electrical, and/or fluid connection, with or without intervening elements. Further, the D1-axis, the D2-axis, and the D3-axis are not limited to three axes of a rectangular coordinate system, such as the x, y, and z-axes, and may be interpreted in a broader sense. For example, the D1-axis, the D2-axis, and the D3-axis may be perpendicular to one another, or may represent different directions that are not perpendicular to one another. For the purposes of this disclosure, “at least one of X, Y, and Z” and “at least one selected from the group consisting of X, Y, and Z” may be construed as X only, Y only, Z only, or any combination of two or more of X, Y, and Z, such as, for instance, XYZ, XYY, YZ, and ZZ. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.
Although the terms “first,” “second,” etc. may be used herein to describe various types of elements, these elements should not be limited by these terms. These terms are used to distinguish one element from another element. Thus, a first element discussed below could be termed a second element without departing from the teachings of the disclosure.
Spatially relative terms, such as “beneath,” “below,” “under,” “lower,” “above,” “upper,” “over,” “higher,” “side” (e.g., as in “sidewall”), and the like, may be used herein for descriptive purposes, and, thereby, to describe one elements relationship to another element(s) as illustrated in the drawings. Spatially relative terms are intended to encompass different orientations of an apparatus in use, operation, and/or manufacture in addition to the orientation depicted in the drawings. For example, if the apparatus in the drawings is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. Furthermore, the apparatus may be otherwise oriented (e.g., rotated 90 degrees or at other orientations), and, as such, the spatially relative descriptors used herein interpreted accordingly.
The terminology used herein is for the purpose of describing particular embodiments and is not intended to be limiting. As used herein, the singular forms, “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Moreover, the terms “comprises,” “comprising,” “includes,” and/or “including,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, components, and/or groups thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. It is also noted that, as used herein, the terms “substantially,” “about,” and other similar terms, are used as terms of approximation and not as terms of degree, and, as such, are utilized to account for inherent deviations in measured, calculated, and/or provided values that would be recognized by one of ordinary skill in the art.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is a part. Terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and should not be interpreted in an idealized or overly formal sense, unless expressly so defined herein.
As illustrated in
Calcium hydroxide solution and Diammonium hydrogen phosphate with the concentrations shown in Table 1 were pumped using a peristaltic pump at a flow rate of 30 ml/min with the exit temperature at 70° C. (controlled using adjusting set temperature of Heater H1). Resulting suspension was collected immediately after exit. The suspension was then centrifuged followed by washing (×2 times) using deionized water. Synthesized samples were then freeze dried using an Alpha 1-2 LD plus freeze dryer.
X-ray Diffraction: XRD analysis confirmed samples to be phase pure hydroxyapatite when compared to ICDD Pattern #09-432 as no other peak was observed in the spectrum (please see
Scanning Electron Microscopy: SEM was performed to analyze morphology and particle size of the samples synthesized. The average particle size was calculated at 1000× and 5000× magnifications about 4 μm as seen in image (a) of
Synthesis of Hydroxyapatite Using Calcium Nitrate Tetrahydrate & Diammonium Hydrogen Phosphate
Phase pure HA: Similarly, reactions were carried out with Diammonium hydrogen phosphate solution and Calcium nitrate tetrahydrate solution with the different concentrations as shown in Table 2 were pumped at a flow rate 30 ml/min with the exit temperature 70° C. The pH was maintained 10 with 3 ml of ammonium hydroxide solution. Then the mixture was centrifuged and filtered and washed twice by de-ionized water.
X-ray Diffraction: confirms the synthesis of Hydroxyapatite when compared to ICDD Pattern #09-432. But another peak was observed in the spectrum near 30 Theta, which was possibly due to unreacted Calcium Hydroxide, as shown in images (a)-(e) of
Ion Substituted Hydroxyapatite: Substituted reactions were carried out with Diammonium hydrogen phosphate solution and Calcium nitrate tetrahydrate solution with the different concentrations as shown in Table 3 were pumped at a flow rate 30 ml/min with the exit temperature 70° C. The pH was maintained 10 with 3 ml of ammonium hydroxide solution. Then the mixture was centrifuged and filtered and washed twice by de-ionized water.
Zinc Substituted Hydroxyapatite (Zn-HA)
X-ray Diffraction: It is clearly seen from XRD pattern (a) of
Scanning Electron Microscopy: SEM was performed to analyze morphology and particle size of the samples synthesized in this study. Images (a) and (b) of
Magnesium Substituted Hydroxyapatite (Mg-HA)
X-ray Diffraction: It is clearly seen from the XRD pattern (a) of
Scanning Electron Microscopy: Scanning Electron Microscopy was performed for morphological analysis of Mg-HA in this study. Images (a) and (b) of
Silicone Substituted Hydroxyapatite (Si-HA)
X-Ray Diffraction: The XRD pattern (a) in
Scanning Electron Microscopy: images (a) and (b) of
Carbonate Substituted Hydroxyapatite (CO3-HA)
X-Ray Diffraction: The XRD pattern (a) of CO3-HA (Sample D) in
Scanning Electron Microscopy: images (a) and (b) of
Synthesis of Zinc Phosphates
For the synthesis of zinc phosphates, stock solutions of 0.15M zinc nitrate and 0.1M di ammonium hydrogen phosphase were prepared in deionized water respectively. For first reaction (Sample A), 250 ml each solution was used and pumped at a flow rate of 30 ml/min. In this reaction no pH was adjusted and no heating was involved.
In a second reaction (Sample B) 250 ml of each solution were pumped at same flow rate but pH was adjusted by adding 3 ml of ammonia solution in the original reagent solutions. The third reaction (Sample C) was again done at same flow rate but no pH adjusted but heating was involved up to 70° C. In the fourth reaction (Sample D), again we used 250 ml of each solution but in this reaction no heating and pH adjustment were involved as shown in Table 4. After collection the suspensions were filtered followed by washing with deionized water (×2 times). All the samples were dried in drying oven at 80° C. for 24 hours.
Table: 4 shows the reactions IDs, reaction parameters, concentrations and volumes of precursors used for synthesis of zinc phosphates in this embodiment.
X-ray Diffraction: When no heating was used without any pH adjustment Zn3 (PO4)2.2H2O phase was observed for Sample A in pattern (a) of
Scanning Electron Microscopy: SEM analysis reveals image (a) of
Synthesis of Phase Pure and Ion Substituted Oxides
Phase Pure Zinc Oxide
Zinc oxide was synthesized using the 0.3M Zn(NO3)2.6H2O and 0.6M NaOH solutions with a flow rate of 30 ml/min with exit temperature of 70° C. The synthesized samples were then freeze dried for 24 hours to obtain phase pure ZnO.
X-ray Diffraction: pattern (a) of
Scanning Electron Microscopy: images (a) and (b) of
Ion Doped Zinc Oxides
To synthesize doped-Zinc oxides, pre-weighed dopant sources [Ce(NO3)3.6H2O, KNO3, Ca(NO3)2.4H2O, Mg(NO3)2.6H2O, & Fe(NO3)3.9H2O] were added to Zinc Nitrate solution.
Cerium, Potassium, Magnesium, Calcium and Iron ions were doped in Zinc Oxide in varying (theoretical) concentrations (0.5 mole %, 1 mole % & 2 mole %). Please see Table 5 for details.
Table: 5 shows the amounts of dopant ion sources added to Zinc Nitrate precursor solution.
Elemental Analysis (using SEM-EDS): An EDS detector attached to the SEM was used to verify the dopant ions presence in synthesized oxides. The spectra revealed no additional impurities. The results are summarized in Table 6 below. It was observed that the measured dopant amount was generally lesser than the added dopant amount. This difference may be attributed to the high diffusivity of the flow process which provides less (hence quick) residence times. These results elucidate that successful doping was achieved.
X-Ray Diffraction: patterns (a)-(d) of
Furthermore, it was observed that the sharpness of the peak reduces along with shift as the dopant concentration increases. It can be inferred that the dopant affects decreases the crystallinity due to ZnO lattice distortion.
Coupled with the confirmation of doping from EDS elemental analysis, the shift in peaks confirms the incorporation of dopant ions in the ZnO lattice. In all the cases, the observed samples were found to be phase-pure (i.e. no other oxides were detected). It is evident that the dopants have broadened the spectra which depicts change in particle size; which were then validated by SEM results.
Scanning Electron Microscopy: Scanning Electron Microscopy was used to investigate the effect of dopant concentrations on particle morphology and aggregation.
Images (a) and (b) of
At lower concentration of potassium i.e. 0.5 mole %, the nanoparticles were clustered together and formed agglomerates, the high magnification images (a) and (b) of
The calcium doping at 0.5 mole % resulted in agglomeration of nanoparticles. The image (a) at low magnification of
0.5 mole % Fe doped ZnO depicted very small independent features of about 33.194 nm to 126.399 nm at low magnification. However, at high magnification the fused entities were spotted (˜72.05812 nm), as shown in images (a) and (b) of
Similarly, the doping of Mg to ZnO lead to particle growth when the dopant concentration was increased to 2%, as shown in images (e) and (f) of
Phase Pure Cerium Oxide Synthesis
Cerium oxide was synthesized using the reagents cerium nitrate tetra hydrate (0.1M in 250 ml water) and sodium hydroxide (1M in 250 ml water) at a flow rate of 30 ml/min. The synthesized sample was freeze dried at 4000 rpm followed by twice washing.
X-Ray Diffraction: XRD pattern shown in
Scanning Electron Microscopy: Scanning Electron Microscopy of CeO2 was performed to analyze particle size and morphology.
Grafted Oxides
Surface modification using the flow synthesis system was carried out. A monomer urethane dimethacrylate (UDMA) was grafted onto ZnO particles by utilizing a third stream in the pumps.
Although certain exemplary embodiments and implementations have been described herein, other embodiments and modifications will be apparent from this description. Accordingly, the inventive concepts are not limited to such embodiments, but rather to the broader scope of the appended claims and various obvious modifications and equivalent arrangements as would be apparent to a person of ordinary skill in the art.
This application is a Continuation-in-Part of U.S. patent application Ser. No. 16/373,185, filed on Apr. 2, 2019, and claims priority from and the benefit of Pakistan Patent Application No. 378/2018, filed on May 30, 2018, which are hereby incorporated by reference for all purposes as if fully set forth herein.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16373185 | Apr 2019 | US |
| Child | 16425295 | US |
