400 increases, a larger turbulent flow is created in the wells to enable shaking. Particularly, if the turning angle is out of the range defined above, the magnetic particles present in the wells may escape from the wells. It is particularly preferable that when a mixture of the magnetic particles and a liquid is dispensed into the wells, the operating angle of the shaker is adjusted such that the liquid does not flow out of the wells. That is if the turning angle of the seesaw-type shaker 400 exceeds −45 to +45°, the magnetic particles dispensed into the well may flow out and be lost, which is why the cost used for one inspection may rise. For the purpose of preventing magnetic particles from escaping, it is necessary to use a multi-well plate having wells whose size is larger than magnetic particles dispensed into the wells or to reduce the number of magnetic particles dispensed into the wells, which reduces the efficiency of the diagnostic device. Meanwhile, if the turning angle of the seesaw-type shaker is in the range of −10 to +10°, the dispersibility of the magnetic particles by the seesaw-type shaker may be reduced. Accordingly, the seesaw-type shaker is preferably turned at an angle in the range of −45 to +45° about its turning axis. The turning angle is more preferably in the maximum range of −45 to +45° and in the minimum range of −10 to +10°, most preferably in the maximum range of −25 to +25° and in the minimum range of −20 to +20°.

The demagnetizer 300 is provided to remove the remanence of the magnetic particles. In the present invention, it is preferable that AC electromagnets are used to remove the remanence of the magnetic particles.

The magnetic force of the magnetic particles can be usually removed by heating to or above their Curie temperature, applying a large impact or using an attenuated alternating magnetic field.

The Curie temperature of a magnetic material refers to a temperature at or above which the magnetism of the magnetic material changes suddenly. Generally, a magnetic material loses its magnetism when heated to or above its Curie temperature. Also in the present invention, the magnetism of the magnetic particles can be removed by heating the magnetic particles to a temperature equal to or higher than their Curie temperature. However, this cannot be practically achieved in the diagnostic device because the Curie temperatures of most metals exceed 500° C.

A strong impact on a metal changes the internal atomic arrangement of the metal, leading to a change in the magnetism of the metal. This can be used to remove the remanence of magnetic particles. However, the magnetic particles used in the present invention are vulnerable to impacts due to their core-shell structure and a uniform and strong impact is difficult to apply on the magnetic particles dispensed into the wells, making it difficult to apply an impact in order to remove the remanence of the magnetic particles.

Therefore, in the present invention, it is preferable to remove the remanence of the magnetic particles using an attenuated magnetic field.

The use of an attenuated magnetic field for the removal of the remanence of the magnetic particles will be described below. When a magnetic field is applied to a magnetic material (for example, a ferromagnetic or superparamagnetic material), the atoms of the magnetic material are arranged in a certain direction along the direction of the magnetic field, allowing the magnetic material to have magnetism. Generally, when the magnetic field is removed, the arrangement returns to its original state and the magnetism of the superparamagnetic material should disappear. However, since the arrangement is maintained in the direction of the magnetic field, some of the atoms may have remanence. Particularly, the remanence of the ferromagnetic material tends to last long. Therefore, the remanence of the magnetic material can be demagnetized by eliminating such directionality and making the electron spin arrangement random. The arrangement is usually randomized by transforming the magnetism of electromagnets into a sine wave shape while attenuating the size of the magnetism. Currently, the internal atomic arrangement of the magnetic particles varies depending on a change in the waveform of magnetic force lines of the electromagnets. This waveform is attenuated when transformed into a sine wave shape, and as a result, the internal atomic arrangement may also be rearranged randomly.

However, since such an attenuated magnetic field is complicated to control, an additional controller is essentially required to manage power supply of the electromagnets.

Thus, in the present invention, the remanence of the magnetic particles is removed by a method other than the above-described method. The method using an attenuated magnetic field having a sine wave shape can be applied to not only magnetic particles using a ferromagnetic material but also magnetic particles using a superparamagnetic material as the core material.

A magnetic field can be attenuated by simply adjusting the distance between the demagnetizer 300 and the magnetic particles because the strength of the magnetic field is in inverse proportion to the distance. Accordingly, the demagnetizer 300 used in the present invention can exhibit the same demagnetization performance as conventional demagnetizers.

Therefore, in the present invention, the demagnetizer 300 may be provided to be movable up and down. Preferably, the demagnetizer 300 descends at a speed of 0.1 to 1000 mm/s after the application of a magnetic force. If the speed of the demagnetizer is less than 0.1 mm/s, the attenuation width of the magnetic force lines per hour is small, making it difficult to perform demagnetization. Meanwhile, even if the speed of the demagnetizer exceeds 1000 mm/s, the attenuation width of the magnetic force lines is excessively large, with the result that the magnetic particles may deviate from the magnetic force lines created by the demagnetizer 300 before demagnetization is performed. In conclusion, the demagnetization can be performed smoothly only when the demagnetizer 300 descends at a speed of 0.1 to 1000 mm/s.

The demagnetizer 300 can use DC power instead of AC power, unlike conventional demagnetizers, due to its ability to create a constant magnetic field. Most existing demagnetizers use AC power because they need to generate magnetic force lines in the shape of sine waves, as discussed above. However, since most diagnostic devices use internal DC power, there is a difficulty in that separate power should be supplied for demagnetization. In contrast, since the apparatus of the present invention uses a constant magnetic force to perform demagnetization, it can use the same power source as the internal power source of existing diagnostic devices, which maximizes the efficiency of power management. In order to further increase demagnetization performance, the direction of current supplied to the demagnetizer 300 can also be periodically switched such that a magnetic field having a sine wave shape is supplied, as in conventional demagnetizers. This can also be simplified such that power supplied to the demagnetizer 300 is periodically cut off to create a kind of magnetic field in pseudo-sine wave format.

The demagnetization rods 310 of the demagnetizer 300 may be disposed at positions corresponding to the wells of the multi-well plate 100. If the demagnetizer 300 simply uses rectangular electromagnets, it is difficult to bring the demagnetizer 300 into contact with the bottom of the supporting means 200 below a predetermined distance and it is impossible to supply a uniform magnetic field to each well. For these reasons, the installation of the demagnetization rods 310 at positions corresponding to the wells enables supply of a uniform magnetic field to the wells. Here, it is preferable that the demagnetization rods 310 demagnetize the magnetic particles in the wells with minimal influence on the adjacent wells. It is thus preferable that the demagnetization rods 310 are cylindrical with a diameter equal to or smaller than the wells. If the diameter of the demagnetization rods 310 is larger than that of the wells, the magnetic force lines generated from the demagnetization rods 310 affect the magnetic force lines supplied to the adjacent wells, with the result that destructive interference may occur, making it difficult to smoothly disperse the magnetic particles.

The demagnetization rods 310 may have a length ranging from 0.1 to 100 mm. Within this range, the demagnetizer 300 and the support means 200 can perform demagnetization at a predetermined distance. If the length of the demagnetization rods is less than 0.1 mm, the demagnetizer 300 may approach and come into contact with the support means 200. The distance between the demagnetizer 300 and the support means 200 may be increased to prevent the demagnetizer 300 from approaching and coming into contact with the support means 200. However, the increased distance between the demagnetizer 300 and the support means 200 may cause poor demagnetization efficiency. Meanwhile, if the length of the demagnetization rods exceeds 100 mm, the space for the demagnetizer 300 increases, resulting in an increase in the size of the diagnostic device, which is inefficient.

The demagnetizer 300 may be fixed to a vertically moving means 320 for its vertical movement. The vertically moving means 320 is connected to the demagnetizer 300, like the moving means moving the support means 200. The vertically moving means 320 may include a motor moving the demagnetizer 300 up and down and a rail which is connected to the demagnetizer 300 and along which the demagnetizer 300 is moved up and down. However, the demagnetizer 300 is moved only vertically, unlike the supporting means. Accordingly, it is preferable that the demagnetizer 300 moves one-dimensionally through along one moving means.

The present invention also relates to a diagnostic system including the demagnetization apparatus. The diagnostic system includes magnetic particles and antibodies and probes bound to the magnetic particles. The diagnostic system can detect target analytes bound to the probes through nucleic acid hybridization or antigen-antibody reactions. To this end, secondary antibodies are bound to the target analytes and fluorescent materials or enzymes are bound to the secondary antibodies to detect the target analytes. In the present invention, a plurality of magnetic particles (particularly microrods) having different lengths are used to detect a plurality of target analytes separately or simultaneously. In addition, since the diagnostic system of the present invention performs demagnetization using magnetic particles, it can minimize aggregation of magnetic particles caused by remanence, achieving much higher accuracy than existing diagnostic systems using magnetic particles.

A method for demagnetizing magnetic particles according to the present invention will be described in detail.

The method includes (i) dispensing magnetic particles into the wells of a multi-well plate, (ii) lifting a demagnetizer such that the uppermost ends of demagnetization rods maintain a predetermined distance from a support means supporting the multi-well plate, (iii) applying power to the demagnetizer to create a magnetic force, (iv) allowing the demagnetizer to descend to demagnetize the magnetic particles in the multi-well plate, and (v) operating a seesaw-type shaker installed in the supporting means to disperse the magnetic particles.

In step (i), magnetic particles are prepared and dispensed into the wells of a multi-well plate. The multi-well plate may be prepared only for demagnetization. Alternatively, the multi-well plate may be one that is used for diagnosis. In this case, the multi-well plate is moved to a position where a demagnetizer is provided to perform demagnetization. The magnetic particles may be fresh magnetic particles that are demagnetized before being used for diagnosis. Alternatively, the magnetic particles may be those that are dispensed into the wells, demagnetized, and regenerated.

In step (ii), a demagnetizer is lifted such that the uppermost ends of demagnetization rods maintain a predetermined distance from a support means supporting the multi-well plate. In step (ii), the demagnetization rods are allowed to approach the support means for demagnetization. Here, it is preferable that power supplied to the demagnetizer and the demagnetization rods is cut off such that the demagnetizer and the demagnetization rods move in a state in which no magnetic field is created. Generally, when a magnetic field approaches a ferromagnetic material and its density increases, the remanence of the ferromagnetic material becomes larger. In step (ii), it is thus preferable that power supplied to the demagnetizer is cut off so as not to increase the remanence of the magnetic particles. The distance between the demagnetization rods and the support means may be 0.1 to 100 mm. If the distance is less than 0.1 mm, the demagnetization rods and the supporting means may be brought into contact with each other during movement or demagnetization, causing their damage. Meanwhile, if the distance exceeds 100 mm, the magnetic particles may not be readily demagnetized by the demagnetizer.

In step (iii), power is applied to the demagnetizer to create a magnetic force. Specifically, power, particularly AC power, is applied to the demagnetizer to allow electromagnets provided in the demagnetizer to create a magnetic field. Here, it is preferable to use the same power as the power supplied to the diagnostic device. It is more preferable to supply a power of 24 V, 3 A.

In step (iv), the demagnetizer is allowed to descend to demagnetize the magnetic particles in the multi-well plate. Specifically, the demagnetizer is moved such that the polarity and strength of the magnetic field supplied to the magnetic particles are changed to demagnetize the magnetic particles. For demagnetization, the demagnetizer preferably descends at a speed of 0.1 to 1000 mm/s, more preferably 10 to 50 mm/s, most preferably 60 mm/s. The demagnetizer preferably descends by 10 to 150 mm, more preferably 40 to 80 mm, most preferably 60 mm. If the demagnetizer descends by less than 10 mm, the magnetic field cannot be reduced to a minimum range, with the result that demagnetization may not be completed, leaving remanence behind. Meanwhile, if the demagnetizer descends by more than 150 mm, only the size of the diagnostic device increases, which is inefficient.

In step (v), a seesaw-type shaker installed in the supporting means is operated to disperse the magnetic particles. In step (v), the demagnetized magnetic particles are additionally dispersed. Even when the demagnetization is completed by the demagnetizer, the position of the magnetic particles in the wells may hardly change. Therefore, it is preferable to uniformly disperse the magnetic particles in the wells with shaking using the seesaw-type shaker.

Preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings such that those skilled in the art can readily practice the invention. In describing the present invention, detailed explanations of a related known function or construction are omitted when it is deemed that they may unnecessarily obscure the essence of the invention. Certain features shown in the drawings are enlarged, reduced or simplified for ease of illustration and the drawings and the elements thereof are not necessarily in proper proportion. However, those skilled in the art will readily understand such details.