Optical reader system and method for monitoring and correcting lateral and angular misalignments of label independent biosensors

Abstract

An optical reader system and method are described herein that can detect a lateral and/or angular misalignment of one or more biosensors so that the biosensors can be properly re-located after being removed from and then reinserted into the optical reader system. In one embodiment, the biosensors are incorporated within the wells of a microplate.

1 . A method for detecting and correcting a misalignment of a microplate in an optical reader system, said method comprising the steps of:
 placing said microplate onto a holder;   using a fiducial marking on said microplate to determine a first position of said microplate;   removing said microplate from said holder;   re-inserting said microplate back onto said holder;   using said fiducial marking on said microplate to determine a second position of said microplate;   comparing the first position and the second position of said microplate; and
 if there is a difference between the two positions, then addressing the lateral and/or angular misalignment of said microplate such that the re-inserted microplate is positioned to be located at or substantially near to the first position, wherein said fiducial marking on said microplate is a coating. 
   
     
     
         2 . The method of  claim 1 , wherein said addressing step includes the step of moving said holder so that the microplate is located at or substantially near to the first position. 
     
     
         3 . The method of  claim 1 , wherein said addressing step includes the step of moving one or more optical beams used to interrogate said fiducial marking so that the microplate is located at or substantially near to the first position. 
     
     
         4 . The method of  claim 1 , wherein said addressing step includes the step of using software to adjust a measured interrogation reading based upon the known position error and a known translation sensitivity. 
     
     
         5 . The method of  claim 1 , wherein said step of using the fiducial marking on said microplate to determine either the first position or the second position of said microplate includes:
 generating an optical beam;   scanning the optical beam across said fiducial marking on said microplate;   collecting the scanned optical beam which is reflected from said fiducial marking on said microplate;   processing the collected optical beam to determine either the first position or the second position of said microplate as a function of a position of said holder; and   recording either the first position or the second position of said microplate as a function of the position of said holder.   
     
     
         6 . The method of  claim 1 , further comprising the step of determining whether or not a biological substance is present or a biomolecular event occurred on a surface of a measurement diffraction grating within a well in said microplate. 
     
     
         7 . The method of  claim 6 , wherein said determination of the second position of said microplate and said determination of whether or not a biological substance is present or a biomolecular event occurred within the well in said microplate are performed in one optical beam scanning step. 
     
     
         8 . The method of  claim 6 , wherein said determination of the second position of said microplate and said determination of whether or not a biological substance is present or a biomolecular event occurred within the well in said microplate are performed in two optical beam scanning steps. 
     
     
         9 . The method of  claim 1 , further comprising the step of scanning multiple fiducial markings on said microplate to measure thermal dilations of said microplate. 
     
     
         10 . The method of  claim 1 , further comprising the step of scanning the fiducial marking which is a fiducial diffraction grating to determine a temperature gradient. 
     
     
         11 . The method of  claim 1 , further comprising the step of scanning the fiducial marking which includes features that are at one angle to a scanning direction of an optical beam and features that are at a second angle to the scanning direction of the optical beam which enables one to determine misalignments if any in two directions. 
     
     
         12 . An optical reader system comprising:
 a holder for supporting a biosensor;   a light source for creating an optical beam which is scanned across a fiducial marking associated with the biosensor;   a detector for collecting the scanned optical beam which is reflected from the fiducial marking associated with the biosensor;   a processor for analyzing the collected optical beam and determining a position of the biosensor; and   said processor for addressing a lateral and/or an angular misalignment of the biosensor, if needed.   
     
     
         13 . The optical reader system of  claim 12 , wherein said fiducial marking is a fiducial diffraction grating which is located away from a measurement diffraction grating that is associated with the biosensor. 
     
     
         14 . The optical reader system of  claim 12 , wherein said fiducial marking includes features that are at one angle to a scanning direction of the optical beam and features that are at a second angle to the scanning direction of the optical beam which enables one to determine misalignments if any in two directions. 
     
     
         15 . The optical reader system of  claim 12 , wherein said biosensor is incorporated within a microplate. 
     
     
         16 . A microplate comprising:
 a frame including a plurality of wells formed therein, each well incorporating a biosensor that includes:
 a substrate; 
 a measurement diffraction grating; and 
 a waveguide film; and 
   said frame further includes at least one fiducial marking located thereon which is used to help determine a position of the biosensors.   
     
     
         17 . The microplate of  claim 16 , wherein one of said at least one fiducial marking is located outside the wells. 
     
     
         18 . The microplate of  claim 16 , wherein said fiducial marking is:
 a grating area having a different resonance wavelength;   a fiducial diffraction grating; or   a coating.