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

• US 20060139641A1
• Filed: 08/23/2005
• Published: 06/29/2006
• Est. Priority Date: 12/29/2004
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Gollier, Jacques, Piech, Garrett A., Webb, Michael B.
• Granted Patent: US 7,629,173 B2
• Time in Patent Office: Days
• US Class Current: 356/399
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide

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.

Claims

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.

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. The method of claim 1, wherein said fiducial marking is:

a non-responding line located on the measurement diffraction grating;

a grating area having a different resonance wavelength;

an edge of the measurement diffraction grating;

a fiducial diffraction grating;

or

a coating.

24. The optical reader system of claim 12, wherein said biosensor is incorporated within a microplate.

13. 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.

14. The optical reader system of claim 13, wherein said processor addresses the lateral and/or an angular misalignment of the biosensor by moving the optical beam used to interrogate said fiducial marking on the biosensor.

15. The optical reader system of claim 13, wherein said processor addresses the lateral and/or an angular misalignment of the biosensor by using software to adjust a measured interrogation reading.

16. The optical reader system of claim 13, wherein said processor addresses the lateral and/or an angular misalignment of the biosensor by moving the holder.

17. The optical reader system of claim 16, wherein said processor controls the movement of said holder to change if needed an X-position, a Y-position, an X-Y position or an angular position of the biosensor.

18. The optical reader system of claim 13, wherein said detector utilizes a multimode (MM) fiber to collect the scanned optical beam which is reflected from the fiducial marking associated with the biosensor.

19. The optical reader system of claim 13, wherein:

said light source for outputting an optical beam which is scanned across a measurement diffraction grating associated the biosensor;

said detector for collecting the scanned optical beam which is reflected from the measurement diffraction grating associated with the biosensor; and

said processor for analyzing the collected optical beam to determine if a biological substance is present or a biomolecular binding event occurred on a surface of the measurement diffraction grating associated with the biosensor.

20. The optical reader system of claim 13, wherein said fiducial marking is an edge of a measurement diffraction grating that is located associated with the biosensor.

21. The optical reader system of claim 13, wherein said fiducial marking is a non-responding line which is located on a measurement diffraction grating that is associated with the biosensor.

22. The optical reader system of claim 13, wherein said fiducial marking is a fiducial diffraction grating which is located away from a measurement diffraction grating that is associated with the biosensor.

23. The optical reader system of claim 13, 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.

25. 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.

26. The microplate of claim 25, wherein one of said at least one fiducial marking is located within one of the wells.

27. The microplate of claim 25, wherein one of said at least one fiducial marking is located outside the wells.

28. The microplate of claim 25, wherein said fiducial marking is:

a non-responding line located on the measurement diffraction grating;

a grating area having a different resonance wavelength;

an edge of the measurement diffraction grating;

a fiducial diffraction grating;

or

a coating.

29. The microplate of claim 25, wherein said fiducial marking includes features that are at one angle and features that are at a second angle.

30. The microplate of claim 25, wherein each biosensor is a resonant waveguide grating biosensor that has a reference region and a sample region.

31. A biosensor comprising:

a substrate;

a biomolecular sensing diffraction grating;

a position sensing fiducial marking; and

a waveguide film, wherein said biomolecular sensing diffraction grating and said position sensing fiducial marking are located between said substrate and said waveguide film.

32. The biosensor of claim 31, wherein said biomolecular sensing diffraction grating is physically separated from said position sensing fiducial marking.

33. The biosensor of claim 31, wherein said biomolecular sensing diffraction grating is integrated with said position sensing fidicial marking.

34. The biosensor of claim 31, wherein said biomolecular sensing diffraction grating has a wavelength that is different than a wavelength of said position sensing fiducial marking.

35. A non-scanning interrogation system that uses a vision system to obtain an image of a sensor plate which has one or more fiducials thereon and also uses a processor to analyze the image to look at a position of the one or more fiducials and correct if needed a lateral and/or an angular misalignment of the sensor plate.