US00993 8520B2  (IO)  Patent No.:  US 9,938,520 B2  Apr. 10, 2018  (45)  Date of Patent:  c12)  United States Patent  Fabis  (54)  PREPARATION OF SILICA PARTICLES  (71)  Applicant:  QIAGEN GmbH,  Hilden (DE)  (72)  Inventor:  Roland Fabis,  Leverkusen (DE)  (73)  Assignee:  QIAGEN GmbH,  Hilden (DE)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by 142 days.  (21)  Appl. No.:  14/650,645  (22)  PCT Filed:  Dec. 11, 2013  (86)  PCT No.:  PCT/EP2013/076150  §  371 (c)(l),  (2) Date:  Jun. 9, 2015  (87)  PCT Pub. No.:  WO2014/090838  PCT Pub. Date:  Jun. 19, 2014  (51)  Int. Cl.  (52)  U.S. Cl.  CPC .........  C12N 1511013  (2013.01);  C0lG 49106  (2013.01);  C0lG 49108  (2013.01);  ( 58)  Field of Classification Search  CPC ........ C04B 35/62807; C04B 35/62849; C04B  2235/3272; C04B 2235/5436; C04B  2235/5445; C0lP 2006/42; C09C 1/24  (Continued)  Dec. 11, 2012  (EP) ..................................... 12196503  US 2015/0307870 Al  Oct. 29, 2015  (Continued)  (Continued)  The present invention provides a cost-efficient method for  producing particles having a SiO$_{2 }$ containing surface  wherein said method comprises a) providing an aqueous  reaction composition comprising i) core particles, ii) an  added base, iii) a silicate salt, and iv) a pH modulator  wherein the pH value of the reaction composition is above  the gelation pH value; b) agitating said reaction composi› tion, wherein the pH modulator decreases the pH value of  the reaction composition over time and wherein due to said  decrease of the pH value of the reaction composition SiO$_{2 }$ is deposited onto the core particles, whereby particles are  formed which have a diameter of 30 µm or less; and c)  obtaining the particles. Furthermore, silica particles having  high nucleic acid binding properties are provided.  (74)  Attorney, Agent, or Firm  - Seed IP Law Group LLP  Primary Examiner  - Hoa T Le  (Continued)  Solberg & Landry, Adsorption of DNA into Mesoporous silica, J.  Phys. Chem. B 2006, ll0, 15261-15268.*  (Continued)  (65)  Prior Publication Data  (30)  Foreign Application Priority Data  (57)  ABSTRACT  OTHER PUBLICATIONS  FOREIGN PATENT DOCUMENTS  U.S. PATENT DOCUMENTS  (56)  References Cited  (Continued)  35 Claims, 4 Drawing Sheets  2 µg  4µg  6µg  Bµg  10µg  12µg  14µg  16µg  18µg 20µg  B32B 5116  C0JB 33/113  (2006.01)  (2006.01)  DE  DE  10 2006 054 173 Al  10 2008 063 001 Al  5/2008  6/2010  2,885,366 A  3,678,144 A  5/1959 Iler  7/1972 Shoup 