Sensor and method for measuring the areal density of magnetic nanoparticles on a micro-array

Abstract

The present invention relates to a method and a device for magnetic detection of binding of biological molecules on a biochip. A magnetoresistive sensor device for measuring an areal density of magnetic nanoparticles on a micro-array, the magnetic nanoparticles ( 15 ) being directly or indirectly coupled to the target sample ( 11 ), is described. The magnetoresistive sensor device comprises a substrate ( 3 ) having attached thereto binding sites ( 9 ) able to selectively bind target sample ( 11 ), and a magnetoresistive sensor for detecting the magnetic field of the nanoparticles ( 15 ) coupled to the target sample. The magnetoresistive sensor comprises a plurality of magnetoresistive sensing elements ( 17, 19 ), the width and length dimensions of which are at least a factor 10 or more, preferably a factor 100 or more larger than the diameter of the nanoparticles ( 15 ). A corresponding method is described as well.

1 - 21 . (canceled)  
     
     
         22 . A method for determining the presence or for measuring an areal density of magnetic nanoparticles on a substrate, comprising the steps of: 
 binding a target ( 11 ) to selective binding sites ( 9 ) on the substrate, the target sample ( 11 ) being directly or indirectly labeled with magnetic nanoparticles ( 15 ),    sensing the presence of the bound magnetic nanoparticles ( 15 ) to a binding site to thereby determine the presence or density of the target ( 11 ) labeled with magnetic nanoparticles    wherein the sensing step is carried out by extracting two signals derived from the magnetic field generated by nanoparticles bound to the one binding site using magnetoresistive sensors elements; and    determining the difference between the two signals.    
     
     
         23 . The method according to  claim 22 , wherein a magnetic field is applied perpendicular to the magnetoresistive sensing elements.  
     
     
         24 . The method according to  claim 22 , wherein a magnetic field is applied parallel to the magnetoresistive sensing elements.  
     
     
         25 . A method according to any of the  claims 22  to  24 , wherein the sensing step is carried out by means of a magnetoresistive sensor comprising a plurality of giant magnetoresistive (GMR) sensing elements.  
     
     
         26 . A method according to any of the  claims 22  to  24 , wherein the sensing step is carried out by means of a magnetoresistive sensor comprising a plurality of tunnel magnetoresistive (TMR) sensing elements.  
     
     
         27 . A method according to any of the  claims 22  to  24 , wherein the sensing step is carried out by means of a magnetoresistive sensor comprising a plurality of anisotropic magnetoresistive (AMR) sensing elements.  
     
     
         28 . A method according to any of claims  22 ,  25  to  27 , wherein the sensing step is carried out by means of a Wheatstone bridge or a half-Wheatstone bridge.  
     
     
         29 . A method according to any of  claims 22  to  28 , wherein the binding and sensing steps are carried out at a plurality of probe elements ( 7 ) on the micro-array ( 1 ).  
     
     
         30 . A method according to any of  claims 22  to  29 , wherein the magnetic nanoparticles are superparamagnetic.  
     
     
         31 . A method of detecting a target in a fluid, comprising the steps of: 
 binding a target ( 11 ) to selective binding sites ( 9 ) on a substrate, the target sample ( 11 ) being directly or indirectly labeled with magnetic nanoparticles ( 15 ),    sensing the presence of the bound magnetic nanoparticles ( 15 ) to a binding site to thereby determine the presence or density of the target ( 11 ) labeled with magnetic nanoparticles    wherein the sensing step is carried out by extracting two signals derived from the magnetic field generated by nanoparticles bound to the one binding site using magnetoresistive sensors elements; and    determining the difference between the two signals.    
     
     
         32 . A method as claimed in  claim 31 , wherein the fluid is blood.  
     
     
         33 . A method as claimed in  claim 31 , wherein the fluid is urine.  
     
     
         34 . (cancel).  
     
     
         35 . A method for detecting a selected type of monecules in a fluid, whereby an agent containing nanoparticles is introduced in the fluid which agent chemically reacts with said selected type of molecules, thereby forming a target; and whereby the target is detected by a method according  claim 31  to  33 .