Claims for Patent: 4,695,392

Summary for Patent: 4,695,392

Title:	Magnetic particles for use in separations
Abstract:	A process is provided for the preparation of magnetic particles to which a wide variety of molecules may be coupled. The magnetic particles can be dispersed in aqueous media without rapid settling and conveniently reclaimed from media with a magnetic field. Preferred particles do not become magnetic after application of a magnetic field and can be redispersed and reused. The magnetic particles are useful in biological systems involving separations.
Inventor(s):	Whitehead; Roy A. (Hingham, MA), Chagnon; Mark S. (Lowell, MA), Groman; Ernest V. (Brookline, MA), Josephson; Lee (Arlington, MA)
Assignee:	Advanced Magnetics Inc. (Cambridge, MA)
Application Number:	06/744,434
Patent Claims:	1. A magnetically-responsive particle comprising a magnetic metal oxide core generally surrounded by a silane coat to which molecules can be covalently coupled, a mass of the particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninetyfive-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel. 2. The magnetically-responsive particle of claim 1 wherein the metal oxide core includes a group of superparamagnetic crystals. 3. The magnetically-responsive particle of claim 2 wherein the superparamagnetic crystals are comprised of iron oxide including divalent and trivalent iron cations. 4. The magnetically-responsive particle of claim 1 wherein the silane coat generally surrounding the core comprises a bifunctional silane polymeric material bearing a first set of functionalities capable of adsorptively or covalently binding to the metal oxide core and a second set of functionalities capable of covalently coupling to organic molecules. 5. The magnetically-responsive particle of claim 4 wherein the silane polymeric material bears organofunctionalities selected from the group consisting of aminophenyl, amino, carboxylic acid, hydroxyl, sulfhydryl, phenolic and aliphatic moieties. 6. The magnetically-responsive particle of claim 4 wherein the silane polymeric material is formed from silane monomers selected from the group consisting of p-aminophenyltrimethoxysilane, 3-aminopropyltrimethoxysilane, N-2-aminoethyl-3-aminopropyltrimethoxysilan e, n-dodecyltriethoxysilane and n-hexyltrimethoxysilane. 7. The magnetic particle of claim 4 wherein the mean diameter thereof as measured by light scattering is between about 0.1.mu. and about 1.5.mu.. 8. The magnetic particle of claim 7 wherein the surface area thereof as measured by nitrogen gas adsorption is at least about 100 m.sup.2 /gm. 9. The magnetically-responsive particle of claim 4 wherein the silane polymeric material bears organofunctionalities selected from the group consisting of hydrophobic and amphipathic moieties. 10. A magnetically-responsive particle comprising a superparamagnetic iron oxide core generally surrounded by a coat of polymeric silane to which molecules can be covalently coupled, the iron oxide core including a group of crystals of iron oxide, the particle having a mean diameter as measured by light scattering between about 0.1.mu. and about 1.5.mu. and a surface area as measured by nitrogen gas adsorption of at least about 100 m.sup.2 /gm, a mass of the particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninetyfive-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel. 11. A magnetically-responsive particle comprising a ferromagnetic metal oxide core generally surrounded by a coat of polymeric silane to which molecules can be covalently coupled, the metal oxide core including a group of crystals of metal oxide the particle having a mean diameter as measured by light scattering between about 0.1.mu. and about 1.5.mu. and a surface area as measured by nitrogen gas adsorption of at least about 100 m.sup.2 /gm, a mass of the particles being dispersable in aqueous media to form an aqueous dispersion having (a) a fifty-percent-turbidity-decrease settling time of greater than about 1.5 hours in the absence of a magnetic field, and (b) a ninetyfive-percent-turbidity-decrease separation time of less than about 10 minutes in the presence of a magnetic field, the magnetic field being applied to the aqueous dispersion by bringing a vessel containing a volume of the dispersion into contact with a pole face of a permanent magnet, the permanent magnet having a volume which is less than the volume of the aqueous dispersion in the vessel.