Magnetic particles with a closed ultrathin silica layer, method for the production thereof and their use

• US 9,617,534 B2
• Filed: 02/19/2015
• Issued: 04/11/2017
• Est. Priority Date: 06/23/2005
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics GmbH (Siemens AG)
• Original Assignee: Siemens Healthcare Diagnostics GmbH (Siemens AG)
• Inventors: Hennig, Guido, Hildenbrand, Karlheinz
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US14/626,311
• Publication Number:
  US 20150191718A1
• Time in Patent Office: 782 Days
• Field of Search: None
• CPC Class Codes: C12N 15/1013 by using magnetic beads
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: H01F 1/01 of inorganic materials H01F1/44 takes precedence
• CPC Class Codes: H01F 1/112 with a skin H01F1/113 takes precedence
• CPC Class Codes: H01F 1/36 in the form of particles H01F1/346, H01F1/348 and H01F1/38 take precedence
• CPC Class Codes: H01F 41/005 Impregnating or encapsulating insulating of windings H01F41/12

Abstract

A method for producing silicate-containing magnetic particles having a closed and tight silicate layer and high purity. In addition, the novel method prevents an uncontrolled formation of aggregates and clusters of silicates on the magnetite surface, thereby having a positive influence on the properties and biological applications. The method enables depletion of nanoparticulate solid substance particles on the basis of a fractionated centrifugation. The silicate-coated magnetic particles exhibit optimized magnetization and suspension behavior as well as advantageous run-off behavior from plastic surfaces. These highly pure magnetic particles coated with silicon dioxide are preferably used for isolating nucleic acids from cell and tissue samples, whereby the separating out from a sample matrix ensues by means of magnetic fields. The particles are particularly well suited for the automatic purification of nucleic acids, mostly from biological body samples for the purpose of analyzing them with different amplification methods.

Claims

1. A method for production of silica-coated magnetic particles, comprising:

providing magnetic particles;

depositing initial silicate from sodium silicate or silica sol on the magnetic particles to form an initially-coated magnetic particle;

continuously diluting the initially-coated magnetic particles using cross flow microfiltration at constant volumes to reduce a pH value to a neutral pH value.

2. The method of claim 1, wherein the continuous dilution is performed using a cross flow microfiltration for about 12 to 15 hours.

3. The method of claim 2, further comprising purifying a suspension of aqueous sodium silicate and the magnetic particles after reaction using the cross flow microfiltration to remove particulate impurities.

4. The method of claim 3, wherein the cross flow microfiltration is continued until a quality of an outflowing permeate corresponds to a degree of purity of incoming fresh water.

5. The method of claim 1, wherein the cross flow microfiltration is followed by fractionated centrifugation to separate sedimenting iron oxide particles.

6. The method of claim 1, further comprising depleting nanoparticle components from the magnetic particles.

7. The method of claim 6, wherein the silica-coated magnetic particles have a grain size distribution between 0.1 μ

m to 1 μ

m.

8. The method of claim 6, wherein the depletion of the nanoparticle components is accomplished by a centrifugation technique, wherein an initial suspension of aqueous sodium silicate and the magnetic particles is centrifuged, aqueous supernatant is removed, an equal amount of water or buffer is added, and re-suspended.

9. The method of claim 6, wherein the depletion of the nanoparticle components is accomplished by a gravitational technique wherein a percentage of the magnetic particles are settled out, and aqueous supernatant is replaced.

10. The method of claim 1, wherein the silica-coated magnetic particles comprise a silicate layer having a maximum layer thickness of silicate of 5 nm distributed uniformly over a complete surface of the magnetic particles.

11. The method of claim 10, wherein the maximum layer thickness of silicate is 2 nm.

12. The method of claim 10, wherein the maximum layer thickness of silicate is 0.5 nm.

13. The method of claim 10, wherein the silicate layer has a layer thickness of between 0.2 nm to 0.5 nm.

14. The method of claim 1, wherein the silica-coated magnetic particles comprise a magnetite core and a uniformly thick distribution of a homogenous single to multiple molecular closed and tight silicate layer on the magnetite core, wherein the silicate layer has a thickness of 0.2 nm to 5 nm, and the silica-coated magnetic particles have a grain size distribution between 0.1 μ

m and 1 μ

m.

15. A method for production of silica-coated magnetic particles, comprising:

providing magnetic particles;

depositing initial silicate from sodium silicate or silica sol on the magnetic particles to form initially-coated magnetic particles;

continuously diluting the initially-coated magnetic particles to reduce a pH value to a neutral pH value performed using a cross flow microfiltration at constant volumes,

wherein the silica-coated magnetic particles comprise a magnetite core and a uniformly thick distribution of a homogenous single to multiple molecular closed and tight silicate layer on the magnetite core, wherein the silicate layer has a thickness of 0.2 nm to 5 nm, and the silica-coated magnetic particles have a grain size distribution between 0.1 μ

m and 1 μ

m.