Multi-channel swept wavelength optical interrogation system and method for using same

• US 7,999,944 B2
• Filed: 10/23/2008
• Issued: 08/16/2011
• Est. Priority Date: 10/23/2008
• Status: Expired due to Fees

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Dailey, Michael J. Jr., Mudaliar, Deepti J., Caracci, Stephen J., Modavis, Robert A., Webb, Michael B., Wu, Qi, Pastel, David A., Miller, William J.
• Primary Examiner(s): Toatley; Gregory J
• Assistant Examiner(s): Valentin; Juan D
• Application Number:
  US12/256,852
• Publication Number:
  US 20100105148A1
• Time in Patent Office: 1,027 Days
• Field of Search: None
• US Class Current: 356/448
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/39 using tunable lasers
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods

Abstract

A multi-channel swept wavelength optical interrogation system and a method are described herein that enable the interrogation of one or more biosensors which for example could be located within the wells of a microplate. In one embodiment, the optical interrogation system comprises: (a) a tunable laser that emits an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period; (b) a distribution unit that splits the optical beam into a plurality of interrogation beams; (c) an array of optical interrogation units that receive and direct the interrogation beams towards an array of biosensors; (d) the array of optical interrogation units receive a plurality of reflected interrogation beams from the array of biosensors; (e) a data processing device that receives and processes information associated with the reflected interrogation beams to determine for example whether or not there was a biochemical interaction on anyone of the biosensors.

Claims

1. An optical interrogation system comprising:

a tunable laser that emits an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

a distribution unit that splits the optical beam into a plurality of interrogation beams;

an array of optical interrogation units that receive and direct the interrogation beams towards an array of biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors, wherein each biosensor has a signal area and a reference area, and wherein each optical interrogation unit further includes a photo detector with two photodiodes;

said array of optical interrogation units receive a plurality of reflected interrogation beams from the array of biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors;

a data processing device that receives and processes information associated with the reflected interrogation beams; and

a holder that supports the array of biosensors where said holder includes an array of masks, wherein each of the masks blocks a portion of one of the biosensors from being illuminated by one of the interrogation beams, wherein the portion is a central portion between the signal area and the reference area of the one biosensor, and wherein each mask blocks one of the reflected interrogation beams off the corresponding one biosensor from illuminating a gap between the two photodiodes of the photo detectors of the corresponding optical interrogation unit.

2. The optical interrogation system of claim 1, further comprising a wavelength tracking device that tracks the distinct wavelengths of the optical beam emitted from said tunable laser.

3. The optical interrogation system of claim 2, wherein said wavelength tracking device further comprises a Mach-Zehnder interferometer and an etalon.

4. The optical interrogation system of claim 1, further comprising a power tracking device that tracks the power of said tunable laser.

5. The optical interrogation system of claim 1, wherein said array of optical interrogation units further comprises a first optical interrogation unit that includes:

a first fiber launch that receives a first interrogation beam from said distribution unit and outputs the first interrogation beam;

a first lens that collimates the first interrogation beam outputted from said first fiber launch where the collimated interrogation beam illuminates a first biosensor;

said first lens receives a first reflected interrogation beam from the first biosensor; and

a first photo detector that receives the first reflected interrogation beam output from said first lens.

6. The optical interrogation system of claim 5, wherein said first photo detector is located ahead or past a focal point of said first lens.

7. The optical interrogation system of claim 5, wherein said first optical interrogation unit further includes a polarizer through which passes either or both the first interrogation beam and the first reflected interrogation beam.

8. The optical interrogation system of claim 1, wherein said array of optical interrogation units further comprises a first optical interrogation unit that includes:

a first fiber launch that receives a first interrogation beam from said distribution unit and outputs the first interrogation beam;

a first lens that collimates the first interrogation beam outputted from said first fiber launch where the collimated interrogation beam illuminates a first biosensor;

said first lens receives a second reflected interrogation beam from a second biosensor; and

a first photo detector that receives the second reflected interrogation beam output from said first lens.

9. The optical interrogation system of claim 8, wherein said first photo detector is located ahead or past a focal point of said first lens.

10. The optical interrogation system of claim 8, wherein said first optical interrogation unit further includes a polarizer through which passes either or both the first interrogation beam and the second reflected interrogation beam.

11. The optical interrogation system of claim 1, wherein said array of biosensors are located within an array of wells in a microplate.

12. The optical interrogation system of claim 1, wherein said array of optical interrogation units are located in a mechanical housing connected to the holder that supports the array of biosensors.

13. An optical interrogation system comprising:

a tunable laser that emits an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

a distribution unit that splits the optical beam into a plurality of interrogation beams;

an array of optical interrogation units that receive and direct the interrogation beams towards an array of biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors;

said array of optical interrogation units receive a plurality of reflected interrogation beams from the array of biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors; and

a data processing device that receives and processes information associated with the reflected interrogation beams, wherein said data processing device further includes a memory that stores processor-executable instructions and a processor that interfaces with the memory and executes the processor-executable instructions to;

acquire interrogation data obtained by a plurality of photo detectors in said plurality of optical interrogation units where said plurality of photo detectors receive the plurality of reflected interrogation beams from the array of bio sensors;

acquire coarse wavelength data and fine wavelength data from a wavelength tracking device;

acquire power data from a power tracking device which tracks the power of said tunable laser;

track distinct wavelengths of the optical beam emitted from said tunable laser using the coarse wavelength data and the fine wavelength data;

find instants of zero-crossings of fringes associated with the fine wavelength data;

integrate the interrogation data for each biosensor that was received between trigger points which correspond to adjacent instants of the zero-crossings of the fringes associated with the fine wavelength data;

normalize the integrated interrogation data using the power data from the power tracking device;

digitally filter the normalized integrated interrogation data; and

calculate a centroid for each digitally filtered normalized integrated interrogation data to determine a resonant wavelength for each of the biosensors.

14. The optical interrogation system of claim 13, wherein said processor acquires all of the data and determines the resonant wavelength for each of the biosensors at a data rate equal to or faster than 3 Hz and with a baseline noise of less than 100 fm.

15. An optical interrogation system comprising:

a tunable laser that emits an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

a distribution unit that splits the optical beam into a plurality of interrogation beams;

an array of optical interrogation units that receive and direct the interrogation beams towards an array of biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors;

said array of optical interrogation units receive a plurality of reflected interrogation beams from the array of biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors; and

a data processing device that receives and processes information associated with the reflected interrogation beams, wherein said data processing device further includes a field programmable gate array, FPGA, processing board or an application specific integrated circuit, ASIC, which is used to;

acquire interrogation data obtained by a plurality of photo detectors in said plurality of optical interrogation units where said plurality of photo detectors receive the plurality of reflected interrogation beams from the array of bio sensors;

acquire coarse wavelength data and fine wavelength data from a wavelength tracking device;

acquire power data from a power tracking device which tracks the power of said tunable laser;

track distinct wavelengths of the optical beam emitted from said tunable laser using the coarse wavelength data and the fine wavelength data;

generate a trigger point at each instant when a fringe associated with the fine wavelength data crosses an average level where the average level is determined by using a minimum level and a maximum level of a previous fringe period to compute a predicted average level and then comparing a level of a current fringe with the predicted average level;

integrate the interrogation data for each biosensor that was received between each pair of trigger points which are associated with the fine wavelength data; and

normalize the integrated interrogation data using the power data from the power tracking device;

said data processing device further includes a memory that stores processor-executable instructions and a processor that interfaces with the memory and executes the processor-executable instructions to;

digitally filter the normalized integrated interrogation data; and

calculate a centroid for each digitally filtered normalized integrated interrogation data to determine a resonant wavelength for each of the biosensors.

16. The optical interrogation system of claim 15, wherein said FPGA processing board or said ASIC and said processor acquire all of the data and determine the resonant wavelength for each of the biosensors at a data rate equal to or faster than 7 Hz and with a baseline noise of less than 100 fm.

17. A method for interrogating one or more biosensors, said method comprising the steps of:

emitting, from a tunable laser, an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

splitting, at a distribution unit, the optical beam into one or more interrogation beams;

directing, from an array of optical interrogation units, the one or more interrogation beams towards one or more biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors, wherein each biosensor has a signal area and a reference area, and wherein each optical interrogation unit further includes a photo detector with two photodiodes;

receiving, at the array of optical interrogation units, one or more reflected interrogation beams from the one or more biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors;

processing information associated with the reflected interrogation beams; and

said array of biosensors are supported by a holder which includes an array of masks, wherein each of the masks blocks a portion of one of the biosensors from being illuminated by one of the interrogation beams, wherein the portion is a central portion between the signal area and the reference area of the one biosensor, and wherein each mask blocks one of the reflected interrogation beams off the corresponding one biosensor from illuminating a gap between the two photodiodes of the photo detectors of the corresponding optical interrogation unit.

18. The method of claim 17, wherein said step of processing further includes:

determining whether or not there was a biochemical interaction on the one or more biosensors;

or

calibrating a uniformity of surface chemistry and target molecule immobilizations on the one or more biosensors.

21. The method of claim 17, wherein said one or more biosensors are located within a microplate which is used to perform an endpoint or kinetic biochemical assay.

19. A method for interrogating one or more biosensors, said method comprising the steps of:

emitting, from a tunable laser, an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

splitting, at a distribution unit, the optical beam into one or more interrogation beams;

directing, from an array of optical interrogation units, the one or more interrogation beams towards one or more biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors, wherein each biosensor has a signal area and a reference area, and wherein each optical interrogation unit further includes a photo detector with two photodiodes;

receiving, at the array of optical interrogation units, one or more reflected interrogation beams from the one or more biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors;

processing information associated with the reflected interrogation beams;

wherein said step of processing further includes the steps of;

acquiring interrogation data obtained by one or more photo detectors which receive the one or more reflected interrogation beams from the one or more biosensors;

acquiring coarse wavelength data and fine wavelength data from a wavelength tracking device;

acquiring power data from a power tracking device which tracks the power of the emitted optical beam;

tracking distinct wavelengths of the emitted optical beam using the coarse wavelength data and the fine wavelength data;

finding instants of zero-crossings of fringes associated with the fine wavelength data;

integrating the interrogation data for each biosensor that was received between trigger

points which correspond to adjacent instants of the zero-crossings of the fringes associated with the fine wavelength data;

normalizing the integrated interrogation data using the power data from the power tracking device;

digitally filtering the normalized integrated interrogation data; and

calculating a centroid for each digitally filtered normalized integrated interrogation data to determine a resonant wavelength for the one or more biosensors.

20. A method for interrogating one or more biosensors, said method comprising the steps of:

emitting, from a tunable laser, an optical beam which has a predetermined sequence of distinct wavelengths over a predetermined time period;

splitting, at a distribution unit, the optical beam into one or more interrogation beams;

directing, from an array of optical interrogation units, the one or more interrogation beams towards one or more biosensors, wherein each of the optical interrogation units receives one of the interrogation beams and directs the one interrogation beam to one of the biosensors, wherein each biosensor has a signal area and a reference area, and wherein each optical interrogation unit further includes a photo detector with two photodiodes;

receiving, at the array of optical interrogation units, one or more reflected interrogation beams from the one or more biosensors, wherein each of the optical interrogation units receives a directed one interrogation beam as a reflected interrogation beam from one of the biosensors;

processing information associated with the reflected interrogation beams;

wherein said step of processing further includes the steps of;

acquiring interrogation data obtained by one or more photo detectors which receive the one or more reflected interrogation beams from the one or more biosensors;

acquiring coarse wavelength data and fine wavelength data from a wavelength tracking device;

acquiring power data from a power tracking device which tracks power of the emitted optical beam;

tracking distinct wavelengths of the emitted optical beam using the coarse wavelength data and the fine wavelength data;

generating a trigger point at each instant when a fringe associated with the fine wavelength data crosses an average level where the average level is determined by using a minimum level and a maximum level of a previous fringe period to compute a predicted average level and then comparing a level of a current fringe with the predicted average level;

integrating the interrogation data for each biosensor that was received between each pair of trigger points which are associated with the fine wavelength data; and

normalizing the integrated interrogation data using the power data from the power tracking device;

digitally filtering the normalized integrated interrogation data; and

calculating a centroid for each digitally filtered normalized integrated interrogation data to determine a resonant wavelength for the one or more biosensors.