JPWO2006126504A1 - Silver-coated particles and uses thereof - Google Patents

Abstract

It is an object of the present invention to provide a particle carrier capable of preventing the outflow of particle core components from the particle carrier and capable of stably binding a physiologically active substance. The present invention relates to a silver-coated magnetic particle in which a particle core component containing a magnetic material is coated with silver.

Description

  The present invention relates to silver-coated particles, silver-coated particles to which a biological substance or a physiologically active substance is bound, a method of performing an enzymatic reaction using silver-coated particles, and a method of separating, detecting or storing a substance using silver-coated particles. .

  Conventionally, various methods for isolating a target biological substance from a sample containing nucleic acid, peptide, carbohydrate, lipid and the like have been studied. Such methods include extraction and separation using an organic solvent, isolation of a target substance based on the molecular size using a molecular sieve (filter), and a carrier to which a specific biological substance can reversibly bind. A method of isolating by using the method is known. Among them, the method of isolation using a particle carrier has many advantages when simultaneously handling a large number of samples (for example, Patent Document 1). In addition, since the enzyme reaction is performed by binding an enzyme to the particle carrier, and the enzyme bonded to the carrier can be separated and recovered after the reaction is completed, the particle carrier is also useful in the enzyme reaction.

  Among the particle carriers as described above, magnetic particle carriers (magnetic particles) can be easily recovered by applying a magnetic field, so that a device such as a centrifuge is not required and is excellent in convenience (for example, Patent Document 2). When using magnetic particles, the problem is that the reaction system is contaminated by the outflow of the magnetic component from the particles and the activity of the biological substance or physiologically active substance is inhibited. In order to prevent the outflow of such a magnetic component, a coating technique using a polymer has been used exclusively. However, the particle carrier coated with the polymer has a problem of non-specific adsorption in which substances other than the target substance are adsorbed. Moreover, the outflow of the magnetic substance component could not be sufficiently prevented. It is difficult to sufficiently prevent the outflow of the magnetic substance component for fine particles (for example, Non-Patent Document 1) whose magnetic substance is coated with gold, and further, the effect of reducing nonspecific adsorption of biomolecules on the gold surface. Was also low.

On the other hand, use of particles coated with silver has been reported as a conductive material or an electromagnetic shielding material (for example, Patent Documents 3 and 4). However, there is no example in which particles coated with silver are used for the purpose of binding biological substances or physiologically active substances.
JP 2003-116515 A JP 7-82302 A Japanese Patent Laid-Open No. 4-97912 Japanese Patent Laid-Open No. 2-118079 IEEE.Transaction on Magnetics, Vol. 35, No. 5 (1999), p3496-3498

  An object of the present invention is to provide a particle carrier capable of preventing the outflow of particle core components from the particle carrier and stably binding a biological substance or a physiologically active substance.

  As a result of intensive studies to solve the above problems, the present inventors have found that the outflow of the particle core component can be prevented by coating the particle core component with silver, and the present invention has been completed.

  That is, the present invention includes the following inventions.

(1) Silver-coated magnetic particles in which a particle core component containing a magnetic material is coated with silver.

(2) The silver-coated magnetic particle according to (1), wherein the particle core component comprises a ferromagnetic material, an alloy containing the ferromagnetic material, or a polymer material containing these.

(3) The silver-coated magnetic particle according to (1) or (2), which has an affinity ligand on the surface.

(4) The silver-coated magnetic particles according to any one of (1) to (3), wherein a biological substance or a physiologically active substance is bonded to the surface.

(5) The silver-coated magnetic particles according to (4), wherein a biological substance selected from the group consisting of peptides, nucleic acids, carbohydrates and lipids is bound to the surface.

(6) Silver-coated particles having a biological substance or a physiologically active substance bound to the surface.

(7) The silver-coated particle according to (6), wherein the biological substance is bound to the particle surface via an affinity ligand.

(8) The silver-coated particle according to (6) or (7), wherein a biological material selected from the group consisting of peptides, nucleic acids, carbohydrates and lipids is bound to the surface.

(9) Silver-coated particles for binding biological substances or physiologically active substances.

(10) A method of performing an enzyme reaction using silver-coated particles in which an enzyme is bound to the surface.

(11) A method for detecting a substance that interacts with a biological substance using silver-coated particles in which the biological substance is bound to the surface.

(12) A method for separating a target substance from a mixture, characterized in that silver-coated particles having a substance that binds the target substance on the surface thereof are used.

(13) A method of preserving the biological substance or physiologically active substance by binding the biological substance or physiologically active substance to the surface of the silver-coated particles.

(14) The method according to any one of (10) to (13), wherein the core component of the silver-coated particles includes a magnetic substance.

  According to the present invention, there is provided a particle carrier capable of preventing a particle core component from flowing out of the particle carrier and stably binding a biological substance or a physiologically active substance.

  This specification includes the contents described in the specification, claims and / or drawings of Japanese Patent Application No. 2005-149938, which is the basis of the priority of the present application.

The results of HPLC analysis when the peptides are incubated in the presence of magnetic particles without a silver coating are shown. Fig. 5 shows a spectrum of MALDI-TOF MS when the peptide is incubated in the presence of magnetic particles without a silver coating. The relationship between peptide cleavage rate and time in the presence of silver-coated magnetic particles or magnetic particles without silver coating is shown. Figure 2 shows an HPLC chart of a peptide solution incubated in the presence of silver-coated magnetic particles. Figure 2 shows a MALDI-TOF MS spectrum of a peptide solution incubated in the presence of silver-coated magnetic particles. The relationship between incubation time and the transfer rate of galactose when a glycopeptide is incubated in the presence of MBP-GalT-bound silver-coated magnetic particles and UDP-Gal is shown. The change of the MALDI-TOF MS spectrum when a glycopeptide is incubated in the presence of MBP-GalT-coupled silver-coated magnetic particles and UDP-Gal is shown. The schematic diagram of the silver covering particle | grains of this invention is shown. (A) shows the silver covering particle | grains by which the particle | grain core component was coat | covered with silver. (B) shows silver-coated particles to which biological substances are bound. (C) shows silver-coated particles having an affinity ligand on the surface. (D) shows silver-coated particles in which a biological substance is bound via an affinity ligand. (E) shows a particle in which an affinity ligand is bound to a particle composed entirely of silver including a particle core component.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Silver coating layer, 2 ... Particle nucleus component, 3 ... Biological substance, 4 ... Affinity ligand, 5 ... Particle nucleus component which consists of silver

  The silver-coated particle of the present invention is a particle whose particle core component is coated with silver. The core component is a component that substantially constitutes the particle, and is a component other than the silver coating layer. As the particle core component, those usually used in the art can be used, and there is no particular limitation, and any of inorganic materials and organic materials can be used.

  Inorganic materials include metals such as gold, silver, copper, aluminum, tungsten, cobalt, molybdenum, chromium, platinum, titanium and nickel, alloys such as stainless steel, hastelloy, inconel, monel and duralumin, and metal oxides such as magnetite and ferrite. And laminates of the above metals and ceramics, silicon, silica, glass, fused quartz, synthetic quartz, alumina, sapphire, ceramics, forsterite, and photosensitive glass.

  Organic materials include fluorine resins such as polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF), polyolefins such as polypropylene, polyethylene, polybutene, polystyrene, polyvinyl chloride, polyvinyl alcohol and polyvinyl acetate, nylon (for example, , Nylon 6, Nylon 66, Nylon 11, Nylon 12, Nylon MXD6) and other polyamides, polybutylene terephthalate, polyethylene terephthalate and polytrimethylene terephthalate, and other polyesters, polycarbonate, polyurethane, polylactic acid, ABS resin , Acrylic resin, methylpentene resin, phenolic resin, melamine resin and epoxy Polymeric materials such as resins.

In the present invention, the particle core component is preferably a component containing a magnetic substance. As the component containing a magnetic substance, a component containing a ferromagnetic substance is preferable. Ferromagnetic materials include iron, cobalt, nickel, gadolinium, terbium, dysprosium, holmium, erbium and thulium, and alloys containing these (eg, iron-cobalt alloys), oxides and composite oxides (eg, magnetite (Fe ₃ O ₄ ), maghemite (γ-Fe ₂ O ₃ ), manganese zinc ferrite (Mn _1-x Zn _x Fe ₂ O ₄ ), barium ferrite particles (BaFe ₁₂ O ₁₉ )). The component containing a magnetic material can be in the form of a polymer material containing the magnetic material. As the polymer material, the same materials as described above can be used. In the present invention, particles in which a particle core component containing a magnetic material is coated with silver are referred to as silver-coated magnetic particles. In the present invention, silver-coated magnetic particles include silver-coated magnetic particles. The silver-coated particles also include particles in which the entire particle including the particle core component is composed of silver. Particles containing a magnetic substance as a particle core component are advantageous because they can be easily manipulated by combining them with a magnet.

  The silver-coated particle of the present invention is characterized in that the particle core component is coated with silver. As a method of coating the core component with silver, a method usually used in the art can be used and is not particularly limited. For example, it can be carried out by subjecting particles comprising particle core components to an electroless plating treatment. As electroless plating treatment, (1) a method in which particles are immersed in a solution containing a complexing agent, a reducing agent, etc., and a solution containing silver ions is dropped, and (2) a solution containing silver ions, a complexing agent, etc. A method of dipping the particles and dropping the reducing agent solution, (3) a method of dipping in a solution containing silver ions, a complexing agent, a reducing agent, etc. and dropping caustic alkali are used.

  Examples of the solution containing silver ions include a silver nitrate solution, a silver sulfate solution, a silver acetate solution, a solution in which silver is dissolved in nitric acid, and a solution in which silver is dissolved in sulfuric acid. As the complexing agent, ammonia and / or salts of ethylenediaminetetraacetic acid, nitrotriacetic acid, triethylenetetraminehexaacetic acid, etc. are used. As the reducing agent, formalin, hydrazine and its derivatives, tartaric acid, glucose, alkyl mercaptan and its Derivatives, and allyl mercaptan and derivatives thereof are used.

An embodiment of a method for producing particles in which a core component containing magnetite (Fe ₃ O ₄ ) as a magnetic material is coated with silver is shown below.

Preparation of magnetite particles: 10 g of ferrous sulfate (FeSO ₄ · 7H ₂ O) is dissolved in 100 ml of distilled water. This ferrous sulfate and equimolar sodium hydroxide are dissolved in 50 ml of distilled water. Next, a sodium hydroxide aqueous solution is slowly dropped into the ferrous sulfate aqueous solution while stirring to produce a ferrous hydroxide precipitate. After dropping, the temperature of the suspension is raised to 85 ° C. with stirring, and then oxidized for 8 hours while blowing air using an air pump at a rate of 200 L / hr to generate magnetite particles.

  Preparation of silver-coated particles: To a uniform dispersion obtained by adding 10 g of magnetite particles and 0.1 g of sodium dodecyl sulfate to 30 ml of distilled water, 0.75 g of silver nitrate is added and adjusted to pH 8 with 10% aqueous ammonia. The suspension is heated to 60 ° C., and then 1 ml of 36% formaldehyde solution is added dropwise and stirred for 2 hours. Fine particles are collected by filtration and dried at 100 ° C. for 3 hours. The silver coating amount of the fine particles obtained is about 5% by mass.

  In the silver-coated particles of the present invention, the silver coating amount is usually 0.1 to 20% by mass, preferably 1 to 10% by mass. By setting it as said coating amount, while being able to prevent elution of silver ion reliably, the capability as a magnetic body can also be maintained effectively. The average particle diameter of the silver-coated particles of the present invention is usually 0.05 to 20 μm, preferably 0.1 to 10 μm.

  By covering the particles with silver, the outflow of the particle core components can be effectively prevented. Further, silver is characterized by being stable and unlikely to cause side reactions as compared with other metals. Further, since silver has a bactericidal effect, it can prevent microbial degradation when handling biological materials. Even when silver ions are eluted, precipitation treatment / separation can be performed very simply by adding chloride ions. Moreover, it has the advantage that non-specific adsorption is extremely small compared to other metal coatings.

  Therefore, the silver-coated particle of the present invention is suitable for binding a biological substance or a physiologically active substance to the surface. Examples of the physiologically active substance include various drugs having biological activity in vivo, such as a compound that specifically binds to a receptor in a cell or a cell membrane and generates biological activity. Biological substances include peptides, nucleic acids, lipids, carbohydrates, cells, virus vesicles, and the like. Peptides include oligopeptides, polypeptides and proteins, and peptide derivatives. Proteins include antibodies, enzymes, receptors and the like. Peptide derivatives include fusion peptides fused with other peptides, glycopeptides, chemically modified peptides bound to polymers such as polyethylene glycol, post-translationally modified peptides, and the like. Post-translational modifications of peptides include phosphorylation, acetylation, methylation, myristoylation, glycosylation, amidation and ubiquitination. Nucleic acids include DNA and RNA, as well as single and double stranded nucleic acids. The saccharide includes monosaccharide, oligosaccharide, polysaccharide, glycolipid, glycopeptide, glycoprotein, glycoside and the like. Cells, virus vesicles and the like include intracellular organelles, fungi, liposomes and the like.

  The biological substance or the physiologically active substance can be bound to the silver-coated particles by a method usually used in the art. The bond may be a covalent bond or a non-covalent bond such as an electrostatic bond. For example, a chemical modification group reactive with a biological substance or a physiologically active substance can be introduced on the particle surface, and the biological substance or the physiologically active substance can be bound to the particle surface via the chemical modification group. Examples of the chemically modifying group introduced on the particle surface include an amino group, a carboxyl group, an epoxy group, a formyl group, a hydroxyl group, and an activated ester group. It is also effective to introduce a metal chelate group such as nickel chelate or cobalt chelate. Metal chelating groups are suitable for peptide binding. The chemical modifying group may be introduced to the particle surface via a spacer.

  Biological material can also be bound to the particle surface via an affinity ligand. Accordingly, the present invention also relates to silver-coated particles having an affinity ligand on the particle surface, and silver-coated particles in which a biological substance is bound to the particle surface via the affinity ligand. The affinity ligand is a substance having a property of adsorbing a target biological substance, and those skilled in the art can appropriately select the affinity ligand according to the kind of substance to be bound to the particles. Specific examples of affinity ligands include, for example, amylose, antibodies, histidine tags, silane coupling agents, cellulose derivatives such as nitrocellulose, polycations (polylysine, polyethyleneimine, etc.), linker molecules having reactive ends, and the like. It is done.

  The present invention also relates to a method for performing an enzyme reaction using silver-coated particles having an enzyme bound to the surface thereof. The method of the present invention usually comprises a step of contacting the enzyme-bound silver-coated particles with a substrate and a step of separating the enzyme-bound silver-coated particles from the reaction system. The enzyme-bound silver-coated particles can be separated from the reaction system by filtration, centrifugation, or a method using a magnet. In the case of silver-coated particles containing a magnetic substance as a core component, the particles can be more easily separated without performing centrifugation or the like by a method using a magnet. The separated enzyme-bound silver-coated particles are advantageous from the viewpoint of cost because they can be used again for the enzyme reaction.

  In the enzyme reaction using the silver-coated particles of the present invention, the outflow of the particle core component to the reaction system is prevented, so that the enzyme is not decomposed by the component or the enzyme reaction is not inhibited. It is advantageous when using a magnetic substance having an activity of decomposing a peptide as a component, for example, particles containing magnetite. Moreover, since silver is stable and does not easily cause a side reaction, the enzyme reaction is not inhibited.

  The enzyme that can be used in the enzyme reaction of the present invention is not particularly limited, and any of transferase, oxidoreductase, hydrolase, isomerase, and ligase can be used. For example, as a transferase, a glycosyltransferase, specifically, sialyltransferase, galactose transferase, N-acetylglucosamine transferase, N-acetylgalactosamine transferase, mannose transferase, glucose transferase, fucose transferase , Xylose transferase, glucuronyl transferase sugar and the like.

  The present invention also relates to a method for separating a target substance from a mixture, characterized by using silver-coated particles having a substance that binds the target substance on the surface thereof. Examples of the substance that binds the target substance include a substance that specifically interacts with and binds to the target substance and a substance that adsorbs the target substance. Specific interactions include antigen-antibody reaction, avidin-biotin binding reaction, enzyme-substrate binding reaction, hybridization between nucleic acid complementary strands, ligand-receptor binding reaction, nucleic acid-transcription factor binding reaction and cell adhesion. Examples include a factor binding reaction and a bond forming reaction between a carbonyl group and an oxyamino group or a hydrazide group. Examples of the substance that adsorbs the target substance include the affinity ligand described above. In the present invention, it is preferable to use silver-coated particles having an affinity ligand that binds the target substance, for example, amylose on the surface thereof.

  The mixture to be separated is not particularly limited as long as it can contain a substance that can bind to the substance bound to the silver-coated particles. For example, compound libraries, gene library expression products, cell extracts, Examples include cell culture supernatants, fermented microorganism products, marine organism extracts, plant extracts and the like.

  The separation method of the present invention includes a step of bringing a silver-coated particle having a substance that binds a target substance on the surface thereof into contact with a mixture, and a step of separating the silver-coated particles to which the target substance is bound. The separation of the particles can be carried out by filtration, centrifugation, a method using a magnet, or the like, as in the case of enzyme-bound silver-coated particles. Since silver-coated particles have very little nonspecific adsorption, only the target substance can be separated by the separation method of the present invention, and the selectivity is excellent.

  The present invention also relates to a method for detecting a substance that interacts with a biological substance using silver-coated particles having the biological substance bound to the surface thereof. Biological substance interactions include antigen-antibody reactions, avidin-biotin binding reactions, enzyme-substrate binding reactions, hybridization between nucleic acid complementary strands, ligand-receptor binding reactions, nucleic acid-transcription factor binding reactions, and cells. Specific interactions such as the binding reaction of adhesion factors can be mentioned. The detection method of the present invention includes a step of bringing a silver-coated particle having a biological substance bound to its surface into contact with a sample, and a step of detecting a substance that interacts with the biological substance on the silver-coated particle. By the detection method of the present invention, a substance that interacts with a biological substance bound to silver-coated particles can also be screened. The sample used here is not particularly limited, and examples thereof include compound libraries, gene library expression products, cell extracts, cell culture supernatants, fermented microorganism products, marine organism extracts, plant extracts, and the like. It is done.

  Specific interactions can be detected, for example, by methods commonly used in the art. Examples thereof include mass spectrometry and a method using a label. Methods using labels include radioisotopes, enzymes such as alkaline phosphatase, acid phosphatase, peroxidase, β-galactosidase, glucose-6-phosphate dehydrogenase and luciferase, and fluorescent agents such as fluorescein, rhodamine, Cy3, Cy5. And chemiluminescent molecules. It can also be detected by immunoprecipitation. As mass spectrometry, for example, TOF-MS method can be used.

  Since silver-coated particles have very little non-specific adsorption, only the target interaction can be detected by the detection method of the present invention, and the selectivity is excellent.

  The present invention also relates to a method for preserving a biological material or physiologically active substance by binding the biological substance or physiologically active substance to the surface of silver-coated particles. In silver-coated particles, the outflow of particle core components is prevented, and since silver is stable and does not easily cause side reactions, biological materials or bioactive substances bound to the particles are not decomposed during storage. . In addition, since silver has a bactericidal effect, it can also prevent biological substances or physiologically active substances from being decomposed by microorganisms. In the storage method of the present invention, it is preferable to store silver-coated particles to which a biological substance or a physiologically active substance is bound in a storage solution such as an antifreeze solution.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to the scope of these examples.

(Comparative example) Cleavage of peptide chain by magnetic particles having amylose on the surface Peptide adsorbed on amylose (Mastparan (Polistes): VDWKIGQHILSVL-NH ₂ ) 0.1 mM, magnetic particles having amylose on the surface as an affinity ligand (MagExtractor- Incubation was carried out at room temperature for 48 hours in 500 μl of 100 mM HEPES buffer (pH 7.4, 0.1% NaN ₃ , 0.1% Triton-X 100) containing 50 mg of MBP-magnetic beads (manufactured by Toyobo). The results of HPLC analysis of the peptide are shown in FIG. The spectrum of MALDI-TOF MS at that time is shown in FIG. The part indicated by the arrow represents a fragment generated by cleaving the peptide.

  From the above results, it can be seen that in magnetic particles having no conventional silver coating, magnetite as a particle core component is eluted and the peptide is cleaved by the action of the magnetite.

Example 1 Comparison of Conventional Magnetic Particles and Silver-Coated Magnetic Particles Under the same conditions as in Comparative Example 1, peptide (VDWKKIGQHILSVL-NH ₂ ) was added in the presence of various magnetic particles having amylose on the surface as an affinity ligand. Incubated for 4 days. The magnetic particles used are shown in Table 1.

  FIG. 3 shows the relationship between the peptide cleavage rate and the time determined from the HPLC analysis results. It can be seen from FIG. 3 that the use of magnetic particles coated with silver rather than the conventional magnetic particles shows a value close to the control in which the peptide is less cleaved and none of the particles are present.

  4a and 4b show the HPLC chart and MALDI-TOF MS spectrum of the peptide solution incubated for 2 days in the presence of the silver-coated magnetic particles 2, respectively. From the figure, it can be seen that the peptide incubated in the presence of silver-coated magnetic particles is hardly cleaved even after 4 days. Further, the results obtained using the silver-coated magnetic particles 1 were almost the same as those obtained using the silver-coated magnetic particles 2.

  The above results indicate that in the magnetic particles coated with silver, the magnetite which is a core component is hardly eluted and the peptide is not easily cleaved.

(Example 2) Galactose elongation reaction to glycopeptide using immobilized galactose transferase 0.1 mM glycopeptide (dWdKdKGE (GlcNAc) dHdLdSdVdL-NH ₂ ) (where dW represents the D form of Trp), 500 μl of 100 mM HEPES containing about 36 μg of MBP-GalT (maltose binding protein-recombinant protein of galactose transferase) and silver-coated magnetic particles (20 mg, silver-coated magnetic particles 1 of Example 1) and 1 mM UDP-Gal buffer _{(pH7.4,10mM MnCl 2, 0.1% NaN} 3, 0.1% Triton-X 100) and incubated at room temperature.

  FIG. 5 shows the incubation time and the transfer rate of galactose. Galactose was transferred over time, and the transfer rate was almost 100% after 8 hours. FIG. 6 shows changes in the MALDI-TOF MS spectrum. It can be seen that a difference peak of 162 corresponding to the molecular weight difference of galactose appears before and after the reaction. This indicates that the galactose transferase bound to the silver-coated magnetic particles is functioning. That is, it is shown that in the silver-coated magnetic particles of the present invention, the nuclear component containing the magnetic substance does not easily flow out, so that the enzyme reaction proceeds without the enzyme bound to the particle being decomposed or inhibited. It was.

  The present invention is an automatic biomolecule purification apparatus, rapid analysis of biomolecules, long-term storage of biomolecules and biodegradable substances, rapid separation and purification / repeated use in enzyme reaction, continuous enzyme reaction automation apparatus, sugar chain automatic synthesis apparatus, analysis It can be applied to pre-processing automation equipment.

  All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Claims (14)

  A silver-coated magnetic particle in which a particle core component containing a magnetic material is coated with silver.   The silver-coated magnetic particle according to claim 1, wherein the particle core component includes a ferromagnetic material, an alloy containing the ferromagnetic material, or a polymer material containing these.   The silver-coated magnetic particle according to claim 1 or 2, which has an affinity ligand on its surface.   The silver-coated magnetic particles according to any one of claims 1 to 3, wherein a biological substance or a physiologically active substance is bonded to the surface.   The silver-coated magnetic particle according to claim 4, wherein a biological material selected from the group consisting of peptides, nucleic acids, carbohydrates and lipids is bound to the surface.   Silver-coated particles with biological or bioactive substances bound to the surface.   The silver-coated particle according to claim 6, wherein the biological material is bound to the particle surface via an affinity ligand.   The silver-coated particle according to claim 6 or 7, wherein a biological material selected from the group consisting of peptides, nucleic acids, carbohydrates and lipids is bound to the surface.   Silver-coated particles for binding biological substances or physiologically active substances.   A method of performing an enzyme reaction using silver-coated particles in which an enzyme is bound to the surface.   A method for detecting a substance that interacts with a biological substance using silver-coated particles having the biological substance bound to the surface thereof.   A method for separating a target substance from a mixture, characterized by using silver-coated particles having a substance that binds the target substance on the surface thereof.   A method for preserving a biological material or physiologically active substance by binding the biological substance or physiologically active substance to the surface of silver-coated particles.   The method according to any one of claims 10 to 13, wherein a core component of the silver-coated particles contains a magnetic substance.

Images