Preparation of Magnetic Core-Shell Particles

Abstract

The invention relates to a process for preparing core-shell particles comprising the steps of (i) providing a dispersion of primary magnetic particles having a mean diameter lower than 200 nm in a solvent; (ii) adding one or more (semi-)metal (oxyhydr)oxide(s) and/or one or more precursor(s) of a (semi-)metal (oxyhydr)oxide to said dispersion; (iii) optionally adding a hydrolysis agent for said one or more precursor(s); (iv) injecting the dispersion in a spray dryer; whereby a (semi-)metal (oxyhydr)oxide shell is formed on the magnetic particles during spray drying. The invention also relates to particles obtainable by said process, to a formulation of said particles in a solvent and to the use of said particles or said formulation for RNA or DNA extraction.

Claims

1. A process for preparing core-shell particles comprising the steps of (i) providing a dispersion of primary magnetic particles having a mean diameter lower than 200 nm in a solvent; (ii) adding one or more (semi-)metal (oxyhydr)oxide(s) and/or one or more precursor(s) of a (semi-)metal (oxyhydr)oxide to said dispersion; (iii) optionally adding a hydrolysis agent for said one or more precursor(s); (iv) injecting the dispersion in a spray dryer; whereby a (semi-)metal (oxyhydr)oxide shell is formed on the magnetic particles during spray drying.

2. The process according to claim 1 wherein the primary magnetic particles are iron oxide particles.

3. The process according to claim 2 wherein the weight ratio of iron oxide to the combination of one or more (semi-)metal (oxyhydr)oxide(s) in the dispersion is from 0.1:5 to 5:0.1.

4. The process according to claim 1 wherein the solvent is water or a solvent miscible with water used alone or in combination.

5. The process according to claim 1 wherein the one or more (semi-)metal (oxyhydr)oxide is silica, titanium oxide, aluminum oxide, zirconium oxide, pseudoboehmite, or zinc oxide.

6. The process according to claim 1 wherein the (semi-)metal (oxyhydr)oxide is silica and/or the precursor thereof is a tetraalkyl orthosilicate, colloidal silica or a mixture of both.

7. The process according to claim 1 wherein the hydrolysis agent is an aqueous solution of a gaseous base.

8. The process according to claim 1 wherein step (iv) is performed immediately after step (ii) or, when a hydrolysis agent is present, immediately after (iii).

9. The process according to claim 1 wherein the pressure of the spray dryer is about 1 bar.

10. The process according to claim 1 wherein the outlet temperature of the spray dryer is between 50° C. and 150° C.

11. The process according to claim 1 further including a step (v) of recovering a powder of magnetic particles coated by (semi-)metal (oxyhydr)oxide from an outlet of the spray dryer through magnetization.

12. Particles obtainable by the process as defined in claim 1.

13. The particles according to claim 12 having a density of less than 0.5 g/ml.

14. The particles according to claim 12 having a specific surface area of at least 30 m.sup.2/g.

15. A formulation comprising particles according to claim 12.

16. A method for RNA or DNA extraction comprising contacting RNA or DNA with the particles of claim 12.

Description

DESCRIPTION OF FIGURES

[0096] FIG. 1: TEM micrographs of primary Fe.sub.3O.sub.4 particles obtained by precipitation route

[0097] FIG. 2: XRD pattern of primary Fe.sub.3O.sub.4 particles obtained by precipitation route

[0098] FIG. 3: TEM micrographs of primary Fe.sub.3O.sub.4 particles obtained by milling route

[0099] FIG. 3B: Particle size distribution of primary Fe.sub.3O.sub.4 obtained by milling route measured by DLS

[0100] FIG. 4: TEM micrographs of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1

[0101] FIG. 5: SEM micrographs of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1

[0102] FIG. 6: Energy dispersive X-ray spectrum on SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1

[0103] FIG. 7: XRD pattern of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1

[0104] FIG. 8: Mossbauer spectrum recorded at room temperature of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1

[0105] FIG. 9: 1 wt % formulation of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 1, as a dispersion (left), under a magnetic field (right)

[0106] FIG. 10: TEM micrographs of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 2

[0107] FIG. 11: SEM micrographs of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 2

[0108] FIG. 12: Energy dispersive X-ray spectrum on SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 2

[0109] FIG. 13: XRD pattern of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 2

[0110] FIG. 14: 1 wt % formulation of SiO.sub.2-coated Fe.sub.3O.sub.4 particles obtained in example 2, as a dispersion (left), under a magnetic field (right)

[0111] FIG. 15: SEM micrographs of core-shell particles obtained at different outlet temperature (1,2,3), at different flow rate (1,4) and at different injection pressure (1,5).

[0112] FIG. 16: Scanning electron micrographs of core-shell particles obtained at different mass ratio of TEOS:Fe.sub.3O.sub.4 (1) 0.1366:1; (2) 0.683:1; (3) 1.025:1; (4) 1.366:1

[0113] FIG. 17: TEM micrographs of core-shell particles obtained using a TEOS: Fe.sub.3O.sub.4 of 2.732:1 (left) and using a TEOS:Fe.sub.3O.sub.4 of 0.683:1 (right)

[0114] FIG. 18: Evolution of the bulk density (full line) and specific surface area of the powder (dots) as a function of TEOS:Fe.sub.3O.sub.4 ratio

[0115] FIG. 19: SEM micrographs of core-shell particles with boehmite, with boehmite:Fe.sub.3O.sub.4 ratio of 1.249:1

[0116] FIG. 20: SEM micrographs of core-shell particles with TiO.sub.2, with TiO.sub.2:Fe.sub.3O.sub.4 ratio of 0.683:1

[0117] FIG. 21: Evolution of the cycle threshold (Ct) according to the concentration of MS2.

[0118] FIG. 22: Evolution of the Ct according to the concentration of ORF1 ab gene from SARS-Cov-2.

[0119] FIG. 23: evolution of the Ct according to the concentration of N gene from SARS-Cov-2.

[0120] FIG. 24: Evolution of the Ct according to the concentration of N gene from SARS-Cov-2.

[0121] FIG. 25: Evolution of the Ct according to the concentration of pneumonia virus of mice (PVM).

[0122] Herein, the invention is described with reference to specific examples of embodiments of the invention. It will, however, be evident that various modifications, variations, alternatives and changes may be made therein, without departing from the essence of the invention. For the purpose of clarity and a concise description features are described herein as part of the same or separate embodiments, however, alternative embodiments having combinations of all or some of the features described in these separate embodiments are also envisaged and understood to fall within the framework of the invention as outlined by the claims. The specifications, figures and examples are, accordingly, to be regarded in an illustrative sense rather than in a restrictive sense. The invention is intended to embrace all alternatives, modifications and variations which fall within the spirit and scope of the appended claims.

EXAMPLES

Optional Preliminary Step 0

[0123] The Fe.sub.3O.sub.4 particles used as primary magnetic particles in a dispersion of the process, may be obtained either by a co-precipitation method or by milling.

[0124] For the preparation of 4.64 g of Fe.sub.3O.sub.4 by co-precipitation method, 5.56 g of iron (II) sulfate heptahydrate and 10.8 g of iron (III) chloride hexahydrate salts are first dissolved in 120 ml of a solution of HCl (0.1M). 200 ml of sodium hydroxide solution (2 molar) was heated at 80° C. under argon flow. Then, iron solution was dropped at 3 ml/minute in the hot sodium hydroxide solution under stirring (at least 400 rpm). After complete addition of iron solution, 20 ml of 28% ammonia solution is added under stirring to the black suspension. The suspension is kept under stirring during 30 min. Heating is then stopped and the suspension remains under stirring until the complete cooling at room temperature. The black precipitate is thoroughly washed with deionized and degassed water until pH reached a value of 7. Then, the black precipitate is washed three times with ethanol before drying the powder.

[0125] FIG. 1 shows TEM images of Fe.sub.3O.sub.4 obtained by the precipitation route. FIG. 2 shows XRD pattern of magnetic Fe.sub.3O.sub.4 particles obtained by precipitation. Fe.sub.3O.sub.4 primary particles obtained by the precipitation method have an average size of about 15 nm.

[0126] For the preparation of Fe.sub.3O.sub.4 by milling, a commercial Fe.sub.3O.sub.4 powder from ABCR is used. The powder is dispersed in alcohol to obtain a 30 wt % suspension. Then, the suspension is ball-milled with an attritor during between 60 and 120 minutes to reduce the size of the Fe.sub.3O.sub.4 particles. It should be understood that the duration of ball-milling may depend on the concentration of particles in the solvent. The duration of ball-milling may be adapted in order to obtain the desired particle size. Preferably the particles are treated under an inert atmosphere to avoid any risk of oxidation. This suspension can be used as feed stock Fe.sub.3O.sub.4 suspension for preparing the core-shell particles in the next step or dried to recover Fe.sub.3O.sub.4 particles.

[0127] FIG. 3 shows TEM images of Fe.sub.3O.sub.4 obtained by milling route. Such particles after ball-milling have an average size of about 60 nm.

[0128] FIG. 3B shows the particle size distribution of Fe.sub.3O.sub.4 after ball-milling.

Example 1

[0129] For the preparation of the core-shell particles, 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling (mean diameter of Fe.sub.3O.sub.4 primary particles was of 60 nm) were dispersed in 250 ml of pure isopropanol (99.5%). The suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 23.7 g of tetraethyl orthosilicate (TEOS) is added to the Fe.sub.3O.sub.4 suspension and the weight ratio SiO.sub.2:Fe.sub.3O.sub.4 in this formulation is of 1.366. 25 ml of concentrated ammonia solution (28 to 30 wt %) was added to 225 ml of milliQ water under stirring. The solution with ammonia is then added in one time to the suspension containing the Fe.sub.3O.sub.4 and the TEOS and directly (max 30 seconds) injected by a two-fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor) under 1 bar pressure. Inlet temperature is fixed at 130° C. and outlet at 80° C. A powder is recovered in the cyclone by adding a magnet inside or outside the bowl.

[0130] The process allows to recover about 9.89 g of core-shell particles, with a yield of about 83%. FIG. 4 shows TEM pictures of the powder recovered. We can observe that the particles are formed of a dark heart of Fe.sub.3O.sub.4 and a shell of SiO.sub.2 having a lighter color. These core-shell particles have an average size of 50 nm. The thickness of the light color shell is about 20 nm. Even, if individual nano-core-shell particles can be clearly observed, we can observe that these nano-core-shell particles are linked together which allows to facilitate the recovery of the powder at the end of the process.

[0131] FIG. 5 shows SEM micrographs of the core-shell particles. Based on FIG. 5, particles have an average size between 10 and 30 μm. These particles are characterized by a spongeous morphology. They are formed by the connection of nano-core-shell particles. This morphology is surprising for a spray drying process. In other processes using spray drying, spherical particles are obtained. Here, the morphology presents a very high porosity, with open pores. An open structure has a beneficial effect with regards to the contact with liquid. These open pores will enable the entry of liquid during the extraction. This morphology is thus particularly efficient for the application of extraction processes. The powder is characterized by a very low bulk density of 0.07 g/ml.

[0132] FIG. 6 shows the energy dispersive X-ray spectrum (EDX analysis) performed on the obtained powder. This spectrum confirms the presence of iron and silicon in the powder. Here below is presented the table associated to EDX analysis with different ratio of element present in the powder (gold is due to sample preparation). The table clearly shows that atomic percentage of silicon and iron element are respectively about 28.28 and 24.69.

TABLE-US-00001 TABLE 1 EDX analysis of core-shell partides obtained in example 1 norm. C atom C Error (1 sigma) Element AN Series unn. C wt % wt % (at %) wt % o 8 K-series 16.99 19.88 43.74 2.26 Si 14 K-series 19.28 22.56 28.78 0.83 Fe 26 K-series 33.46 39.16 24.69 1.03 Au 79 M-series 15.73 18.41 3.29 0.63 Total: 85.46 100.00 100.0

[0133] FIG. 7 shows the XRD pattern of the particles. We can clearly observe the peaks attributed to Fe.sub.3O.sub.4 phase (compare with FIG. 2) which proves that the drying process does not modify the nature of the Fe.sub.3O.sub.4 even if the drying is performed under air in presence of oxygen. Encapsulation of Fe.sub.3O.sub.4 by silica coating prevents any oxidation and maintains the magnetic properties of Fe.sub.3O.sub.4. Only a broad peak around 25° 20 can be attributed to the presence of amorphous silica.

[0134] Mössbauer spectroscopy is an excellent technique for probing the oxidation states and the local environment of Fe atoms in oxide materials. The room temperature 57-Fe Mössbauer spectrum of magnetic particles prepared by spray drying method is presented in FIG. 8. Its corresponding Mossbauer parameters are shown in Table 2 below. The Mossbauer spectra at 295 K exhibit well resolved magnetically split sextets, with asymmetric lines indicating different coordination environments for the Fe.sup.3+ and Fe.sup.2.5+ ions which are characteristics of Fe.sub.3O.sub.4. The doublet is related to paramagnetic phase detected at room temperature. The spectrum shows the presence of two distinct six lines hyperfine patterns, indicating two different types of ferromagnetic Fe atoms in the Fe.sub.3O.sub.4 structure which is consistent with the reported Mossbauer results in the literature. Indeed, good quality fit of the Mossbauer spectrum of Fe.sub.3O.sub.4 was obtained by using two sextets attributed to Fe.sup.3+ and Fe.sup.2.5+ components and one paramagnetic doublet. These sextet subspectra are assigned to iron ions located in A and B positions that present different quadrupole splitting which confirm different local environment of Fe ion in Fe.sub.3O.sub.4. The obtained values of the isomer shift and hyperfine fields are consistent with the high spin state of Fe.sup.3+ and Fe.sup.2.5+ ions in Fe.sub.3O.sub.4. The linewidth of Fe for two sites are relatively high which is related to nanosized particles of the material.

TABLE-US-00002 TABLE 2 Mössbauer parameters for core-shell particles obtained in example 1 (δ is Isomer shift, referred to α-iron at 295 K, ΔE.sub.Q quadrupole splitting, Γ-line width, H.sub.hf hyperfine field) Fe.sup.3+ Magnetic 43 at % δ (mm s.sup.−1) 0.42 ΔE.sub.Q (mm s.sup.−1) −0.13 H.sub.hf (T) 47.6 Γ (mm s.sup.−1) 1.13 Fe.sup.2.5+ Magnetic 44 at % δ (mm s.sup.−1)  0.7 mm/s ΔE.sub.Q (mm s.sup.−1) 0.14 mm/s H.sub.hf (T) 43.7 Γ (mm s.sup.−1) 1.17 Fe.sup.3+ Paramagnetic 13 at % δ (mm s.sup.−1) 0.24 mm/s ΔE.sub.Q (mm s.sup.−1)  1.6 mm/s Γ (mm s.sup.−1) 1.29

[0135] FIG. 9 shows the photography of 1 wt % core-shell particles aqueous suspension (left) and the photography of 1 wt % core-shell particles aqueous suspension under a magnetic field (right). It indicates that the particles are characterized by good magnetic properties.

Example 2

[0136] Another example of preparing core-shell magnetic particles consists in using colloidal silica suspension as silica precursor. In this example, 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling were dispersed in 455 ml of milliQ water under stirring. The suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 25 g of colloidal silica suspension (Ludox HS 40) is added to aqueous suspension of Fe.sub.3O.sub.4 particles. The weight ratio SiO.sub.2:Fe.sub.3O.sub.4 is 2:1. The solution is then directly injected by a two fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor) under 1 bar pressure. Inlet temperature is fixed at 240° C. and outlet at 125° C. Powder is recovered in the cyclone by adding inside of the bowl a magnet.

[0137] The process allows to recover about 7.1 g of particles, which corresponds to a yield of about 46.3%. FIG. 10 shows TEM pictures of the powder recovered. We can observe that micronic particles are formed by this method. They are formed by a dark grey heart of Fe.sub.3O.sub.4 and encapsulated in a light grey color matrix of SiO.sub.2. We can observe small primary colloidal silica particles onto the surface of the micronic core-shell particles. FIG. 11 shows SEM micrographs of the obtained particles. Based on FIG. 11, particle size has an average size between 2 and 6 μm. These particles are characterized by a pseudospherical morphology and a smooth surface and a bulk density of 0.41 g/ml. FIG. 12 shows the energy dispersive X-ray spectrum (EDX analysis) performed on this sample. This spectrum confirms the presence of iron and silicon in the powder. The table below is associated to EDX analysis with different ratio of element present in the powder (gold is due to sample preparation). The table shows that atomic percentage of silicon and iron element are respectively about 22.8 and 18.16.

TABLE-US-00003 TABLE 3 EDX analysis of core-shell particles obtained in example 2 norm. at. Error (1 sigma) Element AN Series wt % norm. wt % %) wt % O 8 K-series 26.49 31.93 57.65 3.08 Si 14 K-series 22.82 27.51 28.29 0.97 Fe 26 K-series 18.17 21.90 11.33 0.57 Au 79 M-series 15.47 18.66 2.74 0.61 Total: 82.95 100.00 100.0

[0138] FIG. 13 shows XRD pattern of the obtained particles. We can observe the peaks attributed to Fe.sub.3O.sub.4 phase (compared with those of FIG. 2) which proves that drying process does not modify the nature of Fe.sub.3O.sub.4. Encapsulation of Fe.sub.3O.sub.4 by silica coating prevents any oxidation and guarantees the magnetic properties of Fe.sub.3O.sub.4. Only a broad peak around between 20 and 25° 20 can be attributed to the presence of amorphous silica. FIG. 14 shows the photography of 1 wt % aqueous suspension of particles obtained in example 2 (left) and the photography of 1 wt % aqueous suspension of particles obtained in example 2 under a magnetic field (right) which confirms that the particles are characterized by good magnetic properties. RNA extraction of Pneumovirus of mice has been performed with those particles under the same protocol as example 1. Particles are characterized by a CT value of 25.0.

Example 3

[0139] As a further example, the conditions of outlet temperature, flow rate and injection pressure were varied. Core-shell particles were prepared in a similar manner as in example 1.

[0140] 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling were dispersed in 230 ml of pure isopropanol (99.5%). Suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 23.7 g of tetraethyl orthosilicate (TEOS) is added to the Fe.sub.3O.sub.4 suspension and weight ratio TEOS/Fe.sub.3O.sub.4 in this formulation is of 1.366. 25 ml of concentrated ammonia solution (28 to 30% mass) was added to 225 ml of milliQ water under stirring. The solution with ammonia is then added in one time to the suspension containing the Fe.sub.3O.sub.4 and the TEOS and directly injected by a two-fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor). Injection pressure is varied between 1 and 3 bar, outlet temperature between 60 and 100° C. and flow rate between 25 and 50 ml/minute to evaluate the robustness of the process. Powder is recovered in the cyclone by adding a magnet inside the bowl.

[0141] Table 4 summarizes the evolution of granulometric factors, bulk density, yield and specific surface area according to the parameters (outlet temperature increasing and decreasing, flow rate and injection pressure). FIG. 15 shows SEM micrographs of the obtained core-shell particles. All have a spongeous morphology with a Si:Fe atomic ratio of 1:1. Modification of outlet temperature (±20° C.) has no effect on the microstructure of the particle. No significant change can be observed concerning size, yield and specific surface area.

[0142] Increase of flow rate and injection pressure does not significantly modify particle size, density, yield and BET specific surface area. The obtained particles present a similar morphology, showing the robustness of the process. All particles obtained are core-shell particles. Hence, this process is highly versatile.

TABLE-US-00004 TABLE 4 Granulometric parameters, bulk density, yield and BET specific surface area for core-shell powders produced using different experimental conditions Effect of outlet temperature Temperature D 0.5 D 0.9 Density Yield Specific surfaces Number (° C.) (μm) (μm) (g/mL) (%) area-BET (m.sup.2/g) 1 81 4.2 10.4 0.065 75.4 60.28 2 61 3.5 7.5 0.066 77.3 not available 3 101 4.1 10.4 0.066 72.4 48.71 Effect of flow rate (ml/min) Flow rate D 0.5 D 0.9 Density Yield Specific surfaces Number (ml/min) (μm) (μm) (g/mL) (%) area-BET (m.sup.2/g) 1 25 4.2 10.4 0.065 75.4 60.28 4 50 3.3 8.3 0.070 75.1 not available Effect of injection pressure injection D 0.5 D 0.9 Density Yield Specific surfaces Number pressure (bar) (μm) (μm) (g/mL) (%) area-BET (m.sup.2/g) 1 1 4.2. 10.4 0.065 75.4 60.28 5 3 3.8 8.8 0.066 70.7 50.74

Example 4

[0143] As a further example, ratio of TEOS versus Fe.sub.3O.sub.4 was varied. Core-shell particles were prepared in a similar manner as in example 1.

[0144] 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling was dispersed in 230 ml of pure isopropanol (99.5%). Suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 2.37, 11.85, 17.78, 23.7 or 47.4 g of TEOS is added to the Fe.sub.3O.sub.4 suspension and weight ratio TEOS/Fe.sub.3O.sub.4 in this formulation is respectively of 0.1366, 0.683, 1.025, 1.366, 2.732. 25 ml of concentrated ammonia solution (28 to 30% mass) was added to 225 ml of milliQ water under stirring. The solution with ammonia is then added in one time to the suspension containing the Fe.sub.3O.sub.4 and the TEOS and directly injected by a two-fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor) under 1 bar pressure. Inlet temperature is fixed at 130° C. and outlet at 80° C. Powder is recovered in the cyclone by adding a magnet inside the bowl.

[0145] Table 5 shows particle size (D.05 and D0.9) and atomic ratio Si/Fe measured by EDX for powder obtained after synthesis following the initial ratio TEOS:Fe.sub.3O.sub.4. Increase of the ratio TEOS:Fe.sub.3O.sub.4 leads to the increase of particle size from 2.1 to 4.4 m for respectively 0.1366:1 to 2.732:1 TEOS:Fe.sub.3O.sub.4 ratio. SEM micrographs (FIG. 16) show a morphological difference between particles according to the TEOS concentration with a more spherical shape at low TEOS:Fe.sub.3O.sub.4 ratio of 0.1366:1. Atomic ratio Si:Fe (Table 5) measured by EDX indicates that the increase of TEOS:Fe.sub.3O.sub.4 leads to enrichment of core-shell particle in Fe.sub.3O.sub.4. This means that the amount of silica shell and thickness of shell can be precisely controlled during the preparation of the solution. TEM micrographs (FIG. 17) clearly shows that thickness of silica shell increases with TEOS:Fe.sub.3O.sub.4 ratio (see larger shell on particles obtained using a TEOS:Fe.sub.3O.sub.4 of 2.732:1, left picture). Specific surface is a key property for surface exchange reaction and kinetic of exchange, specific surface can be modified according to TEOS:Fe.sub.3O.sub.4 ratio as shown in FIG. 18. The highest specific surface was obtained for TEOS:Fe.sub.3O.sub.4 ratio 0.683:1 and was 111 m.sup.2/g. Moreover, we can observe that an inverse correlation can be established between bulk density of core-shell powder and specific surface area (FIG. 18), with the lowest bulk density of 0.056 g/ml for the powder obtained with TEOS:Fe.sub.3O.sub.4 0.683:1 which fits with the highest specific surface area value. Adjusting TEOS:Fe.sub.3O.sub.4 ratio allows to define the physico-chemical properties of the core-shell powder and to adapt those for the desired application.

TABLE-US-00005 TABLE 5 Particle size and atomic ratio Si:Fe according to mass ratio of TEOS:Fe.sub.3O.sub.4 Mass ratio of D 0.5 D 0.9 Number TEOS:Fe.sub.3O.sub.4 (μm) (μm) Atomic ratio Si:Fe 1 0.1366:1  2.1 4.3 0.14:1 2 0.683:1 3.2 7.1 0.63:1 3 1.025:1 3.9 9.7 0.82:1 4 1.366:1 4.2 10.4 1.16:1 5 2.732:1 4.4 10.6 1.88:1

Example 5

[0146] To show the versatility of the process, core-shell magnetic particles were prepared using colloidal boehmite suspension, in a similar manner as in example 1.

[0147] For the preparation of the core-shell particles, 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling was dispersed in 230 ml of pure isopropanol (99.5%). Suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 3.12 g or 6.25 g of boehmite powder (Dequadis) is added to 250 ml of milliQ water to obtain a well dispersed boehmite sol to reach a weight ratio boehmite:Fe.sub.3O.sub.4 in the formulation of 0.624 or 1.249. This suspension is added under stirring to Fe.sub.3O.sub.4 suspension and directly injected by a two-fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor) under 1 bar pressure. Inlet temperature is fixed at 130° C. and outlet at 80° C. Powder is recovered in the cyclone by adding a magnet inside the container.

[0148] In Table 6, we can observe that particle size and density do not depend on boehmite:Fe.sub.3O.sub.4 ratio. Size is around 1.8 m with a very narrow distribution with d(0.9) value around 3.2 m. However, boehmite:Fe.sub.3O.sub.4 ratio allows to control the specific surface area and the atomic ratio Al:Fe in the powder. The use of sol boehmite allows to obtain core-shell particles with a high specific surface area with a value of 185 m.sup.2/g for 1.249:1 boehmite:Fe.sub.3O.sub.4 ratio with bulk density of 0.42 g/ml. Control of Al:Fe can be easily achieved through boehmite:Fe.sub.3O.sub.4 ratio in the suspension before spray-drying.

[0149] FIG. 19 shows SEM micrographs of particles obtained after spray-drying. Pseudospherical non agglomerated core-shell boehmite-Fe.sub.3O.sub.4 with narrow size distribution and smooth surface were obtained.

TABLE-US-00006 TABLE 6 particle size, specific surface area and atomic ratio Al:Fe according to the mass ratio of boehmite:Fe.sub.3O.sub.4 BET specific Weight ratio D0.5 D0.9 surface area Density Atomic Boehmite:Fe3O4 (μm) (μm) (m2/g) (g/mL) ratio Al:Fe 0.624:1 1.8 3.2 134 0.46 0.91:1 1.249:1 1.8 3.4 185 0.42 1.18:1

Example 6

[0150] To further show the versatility of the process, core-shell magnetic particles were prepared using titania, in a similar manner as in example 1.

[0151] For the preparation of the core-shell TiO.sub.2—Fe.sub.3O.sub.4 particles, 5 g of Fe.sub.3O.sub.4 powder obtained by ball-milling was dispersed in 230 ml of pure isopropanol (99.5%). Suspension was treated by ultrasonic probe to enhance the dispersion. Under stirring, 16.16 g of titanium (IV) tetraisopropoxide is added to 250 ml of pure isopropanol to obtain a solution to reach a weight ratio TiO.sub.2:Fe.sub.3O.sub.4 in the formulation of 0.682:1. This solution is added under stirring to Fe.sub.3O.sub.4 suspension and directly injected through a two-fluid nozzle into a spray-dryer (GEA NIRO-Mobile Minor) under 1 bar pressure. Due to the high hydrolysis rate of titanium isopropoxide, hydrolysis can be initiated in the presence of isopropanol, without any additional hydrolysis agent being needed. Inlet temperature is fixed at 130° C. and outlet at 80° C. Powder is recovered in the cyclone by adding a magnet inside the bowl.

[0152] FIG. 20 shows SEM micrograph of core shell particles TiO.sub.2—Fe.sub.3O.sub.4 obtained using this process. Micrometric and weakly agglomerated spherical core-shell TiO.sub.2—Fe.sub.3O.sub.4 particles were obtained. Specific surface area for TiO.sub.2—Fe.sub.3O.sub.4 particles is about 204 m.sup.2/g and particle size is around 2.3 m with low size distribution (Table 7). Atomic ratio Ti/Fe in the final product can be controlled through the TiO.sub.2:Fe.sub.3O.sub.4 weight ratio.

TABLE-US-00007 TABLE 7 particle size, specific surface area and atomic ratio Ti:Fe BET specific Atomic Weight ratio D0.5 D0.9 surface Density ratio TiO.sub.2:Fe.sub.3O.sub.4 (μm) (μm) area (m.sup.2/g) (g/mL) Ti:Fe 0.683:1 (TiO.sub.2:Fe.sub.3O.sub.4) 2.3 3.8 204 0.23 1.01:1

Example 7

[0153] In this example, core-shell particles were prepared in an identical manner as for example 1 except that powder was recovered in the cyclone without using a magnet for the recovery. Yield of production was of 45% when not using a magnet, compared to a yield up to 85% when using a magnet. Core-shell powders obtained by this process are characterized by a very low bulk density and particles size around 4.2 μm which may explain that less particles are recovered in the cyclone without using magnetization.

Example 8

[0154] The capacity of extraction of DNA or RNA using the core-shell particles obtained in example 1 was tested using extraction of Escherichia virus MS2 or Pneumonia Virus of mice (PVM). These particles were also successfully used for extraction of SARS-Cov-2 RNA gene (N gene, S gene et ORF1ab). KingFisher™ Flex Magnetic Particle Processor with 96 Deep-Well Head was used.

[0155] Preparation of the plates (Deepwell 96 plates) requested to wash each plate with 600 μl of buffer and then with 600 μl and 900 μl of ethanol 80%. Elution plate was prepared using 50 μl of elution buffer (TrisHCl 5 mM pH8).

[0156] Extraction of pneumovirus genomic RNA from mice containing the J3666 PVM, Escherichia virus MS2 or SARS-Cov-2 RNA was performed using a total volume of 350 μL (328 μl of commercial lysis buffer containing guanidine thiocyanate and 22 μl of Prot K 20 mg/ml). 100 μL of sample to each well of the 96 deepwell sample plate was added and incubated for 2 minutes at RT. 10 μL of commercial extraction control (Diagenode reference DICR-YD-L100 or DICR-CY-L100) were added to each sample well and to the Negative Control as well. 50 μl (15 mg/ml) of suspended in isopropanol magnetic core-shell particles produced as described in example 1 were added for each well and then 515 μl of isopropanol (98%) were added to each one.

[0157] RNA samples of SARS-Cov-2, MS2 or pneumovirus of mice (SH gene) were loaded on PCR plates and both and extraction control genomes were detected using Taqman-RT-q-PCR following manufacturer's recommendations. The volume of reactions was 20 μL. The amount of RNA was 4 μL. The data can be processed with the FastFinder software (v 3.300.3) and results released to GLIMS.

[0158] FIG. 21 shows the evolution of the cycle threshold (Ct) according to the concentration of MS2. This Ct value is representative of the number of cycles of extraction needed before a signal is obtained in the PCR method. The lower the number, the better the sensitivity of the sample is. A low number indicates a high sensitivity. The Ct value is the cycle number at which the sample becomes positive. This is the cycle number at which the signal becomes detectable. The signal detected may be a fluorescent signal. Commercially available magnetic particles may have a Ct value around 35. In this example, Ct is around 24 independently of the concentration of MS2. This indicates that the particles obtained by the present method are detected earlier in the extraction process, which is advantageous for this application.

[0159] FIGS. 22 to 24 show the evolution of the cycle threshold (Ct) according to the concentration of respectively ORF1ab, N Gene and S Gene from SARS-Cov-2. Core-shell particles used allow for a good extraction of genes from SARS-Cov-2 with a very good sensitivity for each gene detected. Ct about 18.28, 21.23, 24.55 and 28.33 for dilutions of respectively of 1, 0.1, 0.01 and 0.001 is measured for ORF1ab gene. For N gene, Ct measured are 18.67, 21.68, 25.16 and 28.52 for dilutions of respectively of 1, 0.1, 0.01, 0.001. For N gene, Ct measured are 19.74, 22.35, 25.37 and 28.94 for dilutions respectively of 0.1, 0.01, 0.001.

[0160] FIG. 25 shows the evolution of the cycle threshold (Ct) according to the concentration of Pneumonia Virus of Mice (PVM). Ct measured are 21.57, 24.97 and 28.46 for dilutions of respectively of 0.1, 0.01, 0.001.