Magnetic particles and methods of producing coated magnetic particles

Abstract

An improved method for separating materials is provided, using colloidal, magnetizable aggregates, optionally silanized, and coated with a one or more layers of novel polysaccharide derivatives. Materials separated by the aggregates of the invention include inorganic and organic molecules, viruses, organelles, and cells. The invention also relates to a kit for separating such materials. The separated materials are useful in analytical and preparative or in diagnostic and therapeutic techniques.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 09 / 891,787, filed Jun. 26, 2001, now U.S. Pat. No. 7,169,168, which in turn is based upon and claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application Ser. No. 60 / 214,657, filed Jun. 28, 2000. These two priority applications are hereby incorporated by reference in their entireties for all purposes.FIELD OF THE INVENTION [0002] This invention relates to a method of obtaining pure organic, inorganic, or biological materials from mixtures containing such materials. More particularly, the invention relates to a method for obtaining pure materials from such mixtures by separations using resuspendable colloidal polysaccharide-coated magnetizable particles. The invention also relates to a process for preparing the magnetizable particles used in such separations, to processes for coating the magnetizable particles, and to processes for preparing no...

AI Technical Summary

Problems solved by technology

These methods, however, are time consuming, and may require complicated, multistep procedures and complex instrumentation.

Furthermore, these techniques do not readily provide aseptic materials, making the usage of the recovered materials unsuitable for therapeutic use, such as in cell transplantation.

Additionally, the lengthy procedures as conventionally practiced reduce the recovery of viable cells and the stability of labile molecules.

The range of particle sizes available is generally limited by the method used to make the particles.

Particles greater than 500 nm in diameter are easily separated magnetically, but settle out at an inconvenient rate.

Particles between 50 and 500 nm can be prepared and coated (Liberti '332 and '531) but the process used is both inconvenient and potentially injurious to the coating material.

The methods described in the literature for attaching msbps to polysaccharides, in particular, dextran, are not satisfactory.

Periodate oxidation, however, is known to weaken the dextran chain, and fission of the dextran chains can lead to loss of attached msbps.

Simple incubation of either dextran or carboxydextran with colloidal magnetic iron oxide particles at room temperature, however, results in a labile coating.

Incubation at elevated temperatures instead improves the stability, but Maruno '457 notes that carboxymethyldextran-coated magnetic particles prepared in this way have poorer stability than those prepared by precipitating magnetite in the presence of the carboxymethyldextran.

As noted above, however, particles prepared by precipitation of magnetite in the presence of a coating material are typically smaller than 50-60 nm, and thus are difficult to separate magnetically.

The use of carboxyalkylethers, however, is not satisfactory.

Carboxyalkylethers with longer alkyl groups are expected to render the polysaccharide coating hydrophobic, leading to unacceptable non-specific binding to the particle surface.