Magnetic micro-particles

Abstract

A magnetic micro-particle (201) comprising one or more magnetic nano-wires (202).

Claims

1. A magnetic micro-particle comprising one or more magnetic nano-wires, wherein the micro-particle is an ellipsoid having an eccentricity between 0.3 and 1; and wherein the one or more nano-wires have a length between 10 nm and 100 nm; and wherein a maximum dimension of the micro-particle is between 1 μm and 1 mm.

2. The magnetic micro-particle as claimed in claim 1, wherein the micro-particle comprises a polymer.

3. The magnetic micro-particle as claimed in claim 1, wherein the magnetic nano-wires are immobilised within the micro-particle.

4. A magnetic micro-particle comprising a plurality of magnetic nano-wires, wherein the micro-particle is an ellipsoid having an eccentricity between 0.3 and 1; and wherein the plurality of nano-wires have a length between 10 nm and 100 nm.

5. The magnetic micro-particle as claimed in claim 4, wherein the plurality of nano-wires are clumped together or oriented in same direction.

6. The magnetic micro-particle as claimed in claim 1, wherein the one or more nano-wires are superparamagnetic.

7. A magnetic micro-particle comprising one or more magnetic nano-wires, wherein the micro-particle is an ellipsoid having an eccentricity between 0.3 and 1; wherein the one or more nano-wires have a length between 10 nm and 100 nm; and wherein the one or more nano-wires comprise magnetite.

8. The magnetic micro-particle as claimed in claim 1, wherein the one or more nano-wires have a ratio of a length to a width of between 2 and 10.

9. A magnetic micro-particle comprising one or more magnetic nano-wires, wherein the micro-particle is an ellipsoid having an eccentricity between 0.3 and 1; wherein the one or more nano-wires have a length between 10 nm and 100 nm; wherein the micro-particle comprises a polymer; and wherein the polymer is polycaprolactone.

10. The magnetic micro-particle as claimed in claim 1, wherein a maximum dimension of the micro-particle is between 10 μm and 300 μm.

11. The magnetic micro-particle as claimed in claim 1, wherein a maximum dimension of the micro-particle is between 50 μm and 100 μm.

12. The magnetic micro-particle as claimed in claim 1, wherein the one or more nano-wires have a length of approximately 50 nm.

13. The magnetic micro-particle as claimed in claim 1, wherein the one or more nano-wires have a ratio of a length to a width of approximately 5.

Description

(1) A number of embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

(2) FIG. 1 shows a flow chart detailing the steps of a method of manufacturing magnetic micro-particles according to an embodiment of the invention;

(3) FIG. 2 shows a schematic of a magnetic micro-particle according to an embodiment of the invention;

(4) FIG. 3 shows a graph of the distribution of the eccentricity of micro-particles made according to an embodiment invention;

(5) FIG. 4 shows a graph of the angular velocity against magnetic field intensity of ellipsoid magnetic micro-particles made according to an embodiment of the present invention; and

(6) FIG. 5 shows a graph of the angle of rotation of the magnetic micro-particles shown in FIG. 4.

(7) Magnetic micro-particles, e.g. containing magnetic nano-particles, can be used to manipulate small volumes of fluid and other material in a variety of ways and for a variety of uses. For example, there are a number of chemical and biomedical uses in which magnetic micro-particles can be used (under the influence of an applied magnetic field) for micro-mixing of liquids, in flow cytometry, for single cell studies, as magnetic tweezers, etc.

(8) FIG. 1 shows a flow chart detailing the steps of a method of manufacturing magnetic micro-particles according to an embodiment of the invention.

(9) In order to make the magnetic nano-wires for the micro-particles, magnetite (Fe.sub.3O.sub.4) nano-wires are synthesised (step 101, FIG. 1) in a hydrolysis reflux reaction of iron(III) (Fe.sup.3+) using two iron precursors: iron(III) chloride (FeCl.sub.3) and iron(II) sulphate (FeSO.sub.4). A solution of the iron precursors containing 420 mM of iron(III) chloride (e.g. in 4M water), 210 mM of iron(II) sulphate (e.g. in 7 M water), and 1 M urea (CO(NH.sub.2).sub.2) is prepared with deoxygenated Milli-Q water and stirred for 10 minutes.

(10) The solution is then added to a round flask with a reflux condenser which is immersed in an oil bath at 90-100 degrees centigrade. When the solution has reached thermal equilibrium with the oil bath the solution is then removed from the oil bath and cooled to room temperature and aged for twelve hours, in which time the water evaporates from the solution and nano-wires precipitate from the solution. The nano-wires produced are then washed four times with purified, deoxygenated water, magnetically decanted and dried at 40 degrees centigrade over a period of ten hours.

(11) In order to make the micro-particles, a first (polymer) solution is made, along with a second (aqueous) solution, to create an emulsion of droplets of the polymer solution in the aqueous solution.

(12) To make the polymer solution, 0.05 mM of unlinked chains of polycaprolactone ([C.sub.6H.sub.10O.sub.2].sub.n) is dissolved in dichloromethane (CH.sub.2Cl.sub.2) to form a solution (step 1, FIG. 1). Benzoyl peroxide ((C.sub.6H.sub.5CO).sub.2O.sub.2) (BPO) is added to this solution as a cross-linking initiator at a concentration of 2.5% by volume (step 2, FIG. 1).

(13) The previously formed nano-wires are then added to the solution (step 3, FIG. 1) at a concentration of 1% weight-to-volume. The solution containing the nano-wires is then sonicated using ultrasonification to disperse the nano-wires evenly throughout the solution (step 4, FIG. 1).

(14) To make the aqueous solution, polyvinyl alcohol ([CH.sub.2CH(OH)].sub.n) is added in a 1.5% weight-to-volume concentration to water to act as a non-surfactant stabiliser for the droplets of the polymer solution to be added to the aqueous solution. The polymer solution (“oil phase”) is then added to the aqueous solution (“water phase”) in a 1:10 ratio (step 5, FIG. 1).

(15) To emulsify the polymer solution into droplets in the aqueous solution, the mixture is shaken at 3,000 rpm for 10 minutes (step 6, FIG. 1). Immediately after this shaking, phosphate-buffered agar at a concentration of 1% is added as a gelling agent to the emulsion and mixed for 5 minutes (step 7, FIG. 1).

(16) As the emulsion is setting under the action of the phosphate-buffered agar, a static magnetic field of 0.4 T is applied to the emulsion (step 8, FIG. 1). The magnetic field acts to cluster the magnetic nano-wires in the droplets of the polymer solution. (Applying a magnetic field of greater than 1 T acts to align the magnetic nano-wires in the droplets of the polymer solution, so that the magnetic nano-wires in each droplet are oriented in the same direction.)

(17) With the magnetic field still applied, the emulsion is hardened in a freezer for ten minutes (step 9, FIG. 1). This immobilises the droplets of the polymer solution so that they can then be cross-linked. Over a period of ten hours at room temperature, and with the magnetic field still being applied, the droplets of the polymer solution are cross-linked (hardened) (step 10, FIG. 1). Applying the magnetic field over this period of time helps to ensure that the magnetic nano-wires in each polymerised and cross-linked micro-particle are oriented in the same direction.

(18) Once the droplets of the polymer solution have hardened (cross-linked) into micro-particles, the set emulsion is heated in a water bath to melt the phosphate-buffered agar. The magnetic micro-particles can then be attracted out of the melted emulsion by applying a magnetic field to obtain the magnetic micro-particles (step 11, FIG. 1).

(19) FIG. 2 shows a schematic of a magnetic micro-particle 201 according to an embodiment of the invention. The cross-linked polymer micro-particle 201 contains a plurality of superparamagnetic nano-wires 202 that are suspended within the micro-particle 201 and oriented in the same direction. Each nano-wire 202 forms a magnetic dipole, such that the magnetic dipoles plurality of nano-wires 202 sum to give the micro-particle 201 an overall magnetic dipole.

(20) Thus, when a magnetic field is applied to the magnetic micro-particle 201, the magnetic field acts on the magnetic dipole of the magnetic micro-particle 201 and causes the superparamagnetic micro-particle 201 to move in the magnetic field. This allows the magnetic micro-particle 201 to be manipulated under the influence of a magnetic field.

(21) As shown in FIG. 2, a rotating magnetic (B) field causes the magnetic micro-particle 201 to rotate. Owing to the superparamagnetism of the micro-particle 201, it respond quickly to the externally applied magnetic field (with the nano-wires in the micro-particle 201 aligning with the magnetic field, e.g. the micro-particle 201 rotates such that the nano-wires therein align with the magnetic field). When the magnetic field is removed, the superparamagnetic nano-wires in the micro-particle 201 relaxes and thus the micro-particle 201 has negligible remanence (residual magnetism) when the magnetic field is removed.

(22) As will be appreciated, a micro-particle or a plurality of micro-particles that are able to be manipulated in this way can be used for a variety of different uses, e.g. for one or more of: in biomedicine: for drug delivery, cell therapy, cell isolation and/or (e.g. modular) tissue engineering; magnetic tweezers; magnetic micro-mixing of fluids; magnetic flow cytometry; in single cell or bacteria studies: fluorescence, magnetic enzyme-linked immunosorbent assays (ELISAs), and/or cell labelling and/or imaging; isolation and/or purification of biological material (e.g. nucleic acids, antibodies and/or other proteins).

(23) FIG. 3 shows a graph of the distribution of the eccentricity of micro-particles made according to an embodiment of the method outlined above with reference to FIG. 1.

(24) In one set of embodiments, the application of the magnetic field to the polymer droplets, as outlined above, in addition to causing the nano-wires to clump together or align in a particular direction, is arranged to stretch out the polymer droplets to form a spheroid shape. The eccentricity,

(25) $\mathrm{.Math.}=\sqrt{\frac{a^2-b^2}{a^2}}$
(where a and b are the respective lengths of the major and minor axes of the spheroid, assuming that the two equatorial axes of the spheroid are of approximately equal length), of micro-particles made according to the method outlined above with reference to FIG. 1, is shown in FIG. 3. This shows that the eccentricity of these micro-particles is between 0.3 and 0.95, with a modal value of approximately 0.65.

(26) FIG. 4 shows a graph of the angular velocity against magnetic field intensity of ellipsoid magnetic micro-particles made according to an embodiment of the present invention.

(27) The ellipsoid magnetic micro-particles made according to an embodiment of the present invention, e.g. as outlined above with reference to FIG. 1, were placed in an oscillating magnetic field having a frequency of 1 Hz. The intensity of the magnetic field was varied between 0.1 mT and 20 mT, and the angular velocity of the magnetic micro-particles was measured (the “Data” shown in FIG. 4). The same measurement was performed for spherical magnetic micro-particles having magnetic nano-particles inside them (the “Prior art” shown in FIG. 4).

(28) FIG. 5 shows a graph of the angle of rotation of the magnetic micro-particles shown in FIG. 4, with a magnetic field strength of 5 mT.

(29) FIGS. 4 and 5 show that the ellipsoid magnetic micro-particles made according to an embodiment of the present invention follow the magnetic field applied to the magnetic micro-particles, even at low field strengths, while the spherical magnetic micro-particles having magnetic nano-particles inside them lag behind the magnetic field, particularly at low field strengths. The magnetic micro-particles made according to an embodiment of the present invention thus have a higher angular velocity, again particularly at low field strengths.

(30) It will be seen from the above embodiment micro-particles containing magnetic nano-wires can be made that have a relatively significant magnetic dipole, owing to the length of the nano-wires and their alignment in each micro-particle. This allows a relatively large torque to be exerted on each of the micro-particles, e.g. when an oscillating magnetic field is applied to the micro-particles. This may be used, when a magnetic field is applied, to rotate the magnetic micro-particles in a fluid containing the micro-particles.

(31) This contrasts to conventional micro-particles containing point magnetic nano-particles which have no length over which to form a meaningful magnetic dipole. Such conventional magnetic micro-particles have non-homogeneous magnetic properties which are difficult to control, particularly for rotating. The presence of nano-wires in the micro-particles of embodiments of the present invention therefore allows the micro-particles to be controlled more easily and to be moved, e.g. rotated, more quickly than micro-particles that simply contain magnetic nano-particles.

(32) The skilled person will appreciate that the embodiment described above is a preferred implementations and thus a magnetic micro-particle or method of manufacturing a magnetic micro-particle as defined by the scope of the claims may not have all of the features described for these embodiments. For example, the mixture of the polymer solution and the aqueous solution may be mixed at any suitable and desired speed to form the emulsion in order to determine the size of the droplets of the polymer solution (and thus the size of the magnetic micro-particles), as micro-particles of a number of different sizes may be required depending on the end application for the micro-particles.