Rapid magnetic biosensor
The present invention relates to methods and (bio)sensor systems. Herein, magnetic fields are applied in order to transport magnetic particles laterally over a sensor surface with analyte specific probes. The methods of the invention allow the specific binding of magnetic particles to the sensor surface, while aspecific and unbound particles are removed.
1. A method, comprising:
providing magnetic particles to a first region of a reaction chamber, the reaction chamber comprising a sensor surface and a second region, the sensor surface having an analyte-specific probe or an analyte-analogue, wherein the first region and the second region are both outside the sensor surface at opposite ends of the reaction chamber and in a plane of the sensor surface, the sensor surface located between the first region and the second region, and wherein a first portion of the magnetic particles comprises an analyte and a second portion of the magnetic particles do not comprise the analyte;
applying, during a first period of time, a first magnetic field gradient using a first magnet, wherein the first magnet is outside the reaction chamber below the plane of the sensor surface, wherein the first magnetic field gradient has a gradient with a component perpendicular to the sensor surface and directed toward the second region, wherein the first magnetic field gradient removes all the magnetic particles from the first region laterally over the sensor surface above a plane of the sensor surface, wherein some or all of the first portion of the magnetic particles becomes bound to the sensor surface, and wherein the second portion and any remaining magnetic particles of the first portion move to the second region;
subsequent to the first period of time, applying, during a second period of time, a second magnetic field gradient within the reaction chamber using a second magnet, wherein the second magnet is outside the reaction chamber below the plane of the sensor surface, wherein the second magnetic field gradient has a component essentially parallel to the sensor surface, wherein the second magnetic field gradient removes all the magnetic particles from the second region laterally over the sensor surface above a plane of the sensor surface, wherein some or all of the remaining first portion of the magnetic particles becomes bound to the sensor surface, wherein the second portion and any still remaining first portion of the magnetic particles move to the first region, and wherein the second period of time starts after the first period of time; and
detecting the first portion of magnetic particles bound to the sensor surface, wherein the first and second magnets are confined to the ends of the reaction chamber such that the first and second magnets do not overlap the sensor surface and no magnet is located directly beneath the sensor surface.
2. The method of claim 1 , further comprising:
repeating at least once the applying of the first and second magnetic field gradients at a reversal frequency.
3. The method of claim 2 , wherein the reversal frequency is greater than 0 Hz and less than 0.1 Hz.
4. The method of claim 1 , wherein the second magnetic field gradient includes applying the second magnetic field gradient in one direction.
5. The method of claim 1 , wherein applying the first and second magnetic field gradients includes applying each of the first and second magnetic field gradients once.
6. The method of claim 1 , further comprising:
providing a dedicated area on the first region outside the sensor surface; and
the dedicated area collecting the magnetic particles prior to the assay.
7. The method of claim 6 , further comprising:
using an inlet, introducing the magnetic particles into the reaction chamber.
8. The method of claim 1 , wherein applying the first magnetic field gradient or the second magnetic field gradient includes transporting the magnetic particles a first distance, wherein the first distance is greater than a second distance.
9. The method of claim 8 , further comprising obtaining the second distance by Brownian motion.
10. The method of claim 1 , further comprising at least one of the first and second magnets generating an out of plane field with smaller in-plane components.
11. The method of claim 1 , wherein a dimension of the sensor surface located between the first region and the second region is at least between 10 micrometers and 30 micrometers.
12. The method of claim 1 , wherein current carrying conductors suitable for attracting the magnetic particles to the sensor surface or to a region outside the sensor surface are absent.
13. The method of claim 1 , wherein the analyte-specific probe is selected from the group consisting of: an oligonucleotide, an antibody or fragment thereof, a lectin, a pharmaceutical compound, a peptide, and a protein.
14. The method of claim 1 , further comprising:
using a magnetic-particle detector, detecting a magnetic field from a magnetic particle or detecting magnetizability of the magnetic particle when subjected to a magnetic detection field.
15. The method of claim 14 , wherein the magnetic particle is bound to the sensor surface.
16. The method of claim 14 , wherein the magnetic-particle detector comprises a magneto-resistive sensor or a Hall sensor.
17. The method of claim 1 , wherein generating the first magnetic field gradient during the first period of time includes generating the first magnetic field gradient while the second magnetic field gradient is switched off.
18. The method of claim 1 , wherein generating the second magnetic field gradient during the second period of time includes generating the second magnetic field gradient while the first magnetic field gradient is switched off.
19. The method of claim 1 , wherein the second magnetic field gradient is stronger than the first magnetic field gradient.