System and method for self-referencing a sensor in a micron-sized deep flow chamber

• US 20060106557A1
• Filed: 11/18/2004
• Published: 05/18/2006
• Est. Priority Date: 11/18/2004
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Mazumder, Prantik, Yuen, Po Ki, Fontaine, Norman H., Mozdy, Eric J., Quesada, Mark A.
• Granted Patent: US 7,285,420 B2
• Time in Patent Office: Days
• US Class Current: 702/87
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/058 Flat flow cell
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/276 with alternation of sample and standard in optical path
• 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
• CPC Class Codes: G01N 2201/108 Miscellaneous
• CPC Class Codes: G01N 2201/1211 for temperature
• CPC Class Codes: G01N 2201/1217 for index of solution, carrying fluids
• CPC Class Codes: G01N 2201/127 Calibration; base line adjustment; drift compensation
• CPC Class Codes: G01N 2201/12723 Self check capacity; automatic, periodic step of checking
• CPC Class Codes: G01N 2201/128 Alternating sample and standard or reference part in one path
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A system and method are described herein for self-referencing a sensor that is used to detect a biomolecular binding event and/or kinetics which occur in a sample solution flowing along side a reference solution in a micron-sized deep flow channel.

Claims

1. A method for self-referencing a sensor associated with a micron-sized deep flow channel, said method comprising the steps of:

directing an optical beam at said sensor which has a sensing region within a sample solution and a reference solution that flow side-by-side another in said micron-sized deep flow channel;

receiving an output optical response from said sensor;

detecting and analyzing the output optical beam to determine a detection signal associated with the sample solution flowing in a detection region of the sensing region of said sensor and to determine a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor; and

subtracting the reference signal from the detection signal so as to generate a corrected detection signal, wherein uncertainties in the detection signal due to environmental conditions and noise generated by components in an interrogation system are reduced in the corrected detection signal.

2. The method of claim 1, wherein said corrected detection signal indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

3. The method of claim 1, wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

4. The method of claim 1, wherein a plurality of said micron-sized deep flow channels and said sensors are incorporated within a multiple sensor plate.

5. The method of claim 1, wherein an interrogation system performs said step of directing the optical beam at said sensor and said step of receiving the output optical beam from said sensor.

6. The method of claim 5, wherein said interrogation system is an angular interrogation system.

7. The method of claim 5, wherein said interrogation system is a spectral interrogation system.

8. The method of claim 1, wherein said step of detecting is performed by a camera.

9. The method of claim 1, wherein said step of detecting is performed by an optical detector.

10. The method of claim 1, wherein said step of analyzing is performed by hardware.

11. The method of claim 1, wherein said step of analyzing is performed by software.

12. The method of claim 1, wherein said micron-sized deep flow channel is capable of generating a plurality of concentration gradients in the sample solution and a computer is capable of analyzing the output optical beam to determine a plurality of detection signals corresponding to said plurality of concentration gradients in the sample solution.

13. A system comprising:

a sensor;

a micron-sized deep flow channel in which a sample solution and a reference solution flow side-by-side to one another in a sensing region of said sensor;

an interrogation system for directing an input optical beam at said sensor and receiving an output optical beam from said sensor;

said interrogation system including a camera for converting the optical beam to an electrical signal representative of an output image;

a computer for analyzing the output image to determine a detection signal associated with the sample solution flowing in a detection region of the sensing region of said sensor and to determine a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor; and

said computer for subtracting the reference signal from the detection signal so as to generate a corrected detection signal, wherein uncertainties in the detection signal due to environmental conditions are reduced in the corrected detection signal.

14. The system of claim 13, wherein said corrected detection signal indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

15. The system of claim 13, wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

16. The system of claim 13, wherein a plurality of said micron-sized deep flow channels and said sensors are incorporated within a multiple sensor plate.

17. The system of claim 13, wherein said interrogation system is an angular interrogation system.

18. The system of claim 13, wherein said interrogation system is a spectral interrogation system.

19. The system of claim 13, wherein said micron-sized deep flow channel is capable of generating a plurality of concentration gradients in the sample solution and said computer is capable of analyzing the output optical beam to determine a plurality of detection signals corresponding to said plurality of concentration gradients in the sample solution.

20. A system comprising:

a sensor;

a micron-sized deep flow channel in which a sample solution and a reference solution flow side-by-side to one another in a sensing region of said sensor;

an interrogation system for directing an input optical beam at said sensor and receiving an output optical beam from said sensor;

said interrogation system including an optical detector for converting the optical beam to separate electrical signals, one each representing a detection signal associated with the sample solution flowing in a detection region of the sensing region of said sensor and another representing a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor; and

a computer/electrical circuit for subtracting the reference signal from the detection signal so as to generate a corrected detection signal, wherein uncertainties in the detection signal due to environmental conditions are reduced in the corrected detection signal.

21. The system of claim 20, wherein said corrected detection signal indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

22. The system of claim 20, wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

23. The system of claim 20, wherein a plurality of said micron-sized deep flow channels and said sensors are incorporated within a multiple sensor plate.

24. The system of claim 20, wherein said interrogation system is an angular interrogation system.

25. The system of claim 20, wherein said interrogation system is a spectral interrogation system.

26. The system of claim 20, wherein said micron-sized deep flow channel is capable of generating a plurality of concentration gradients in the sample solution and said computer/electrical circuit is capable of analyzing the output optical beam to determine a plurality of detection signals corresponding to said plurality of concentration gradients in the sample solution.

27. An interrogation system capable of performing the following steps:

directing an optical beam at a sensor which has a sensing region within a sample solution and a reference solution that flow side-by-side to one another in a micron-sized deep flow channel;

receiving an output optical beam from the sensor;

wherein the output optical beam is detected/analyzed to determine a detection signal associated with the sample solution flowing in a detection region of the, sensing region of said sensor and to determine a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor;

wherein the reference signal is subtracted from the detection signal so as to generate a corrected detection signal; and

wherein the corrected detection signal indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

28. The interrogation system of claim 27, wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

29. The interrogation system of claim 27, wherein a plurality of said micron-sized deep flow channels and said sensors are incorporated within a multiple sensor plate.

30. The interrogation system of claim 27, wherein said interrogation system is an angular interrogation system.

31. The interrogation system of claim 27, wherein said interrogation system is a spectral interrogation system.

32. A microfluidic device comprising:

a micron-sized deep flow channel in which a sample solution and a reference solution flow side-by-side to one another in a sensing region of a sensor such that an interrogation system can direct an input optical beam at the sensor and receive an output optical beam from the sensor, wherein the output optical beam is analyzed by a computer or detector system to determine a detection signal associated with the sample solution flowing in a detection region of the sensing region of the sensor and a reference signal associated with the reference solution flowing in a reference region of the sensing region of the sensor.

33. The microfluidic device of claim 32, wherein the reference signal is subtracted from the detection signal to obtain a corrected detection signal which indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

34. The microfluidic device of claim 32;

wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

35. The microfluidic device of claim 32, wherein said interrogation system is an angular interrogation system.

36. The microfluidic device of claim 32, wherein said interrogation system is a spectral interrogation system.

37. A system comprising:

a sensor;

a micron-sized deep flow channel in which a sample solution and a reference solution flow side-by-side one another in a sensing region of said sensor;

an interrogation system including;

a first optical fiber launch/receive system, positioned over/under the sample solution, for directing an input optical beam at said sensor and receiving an output optical beam from said sensor; and

a second optical fiber launch/receive system, positioned over/under the reference solution, for directing an input optical beam at said sensor and receiving an output optical beam from said sensor;

an optical detection system for receiving the output light from the optical fibers and converting it to an electrical form; and

a computer for analyzing the output signal received by the first fiber launch/receive system to determine a detection signal associated with the sample solution flowing in a detection region of the sensing region of said sensor;

said computer for analyzing the output signal received by the second fiber launch/receive system to determine a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor; and

said computer for subtracting the reference signal from the detection signal so as to generate a corrected detection signal which indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

38. The interrogation system of claim 37, wherein said interrogation system is an angular interrogation system.

39. The interrogation system of claim 37, wherein said interrogation system is a spectral interrogation system.

40. A system comprising:

a sensor;

a micron-sized deep flow channel in which a sample solution and a reference solution flow side-by-side one another in a sensing region of said sensor;

an interrogation system including capable of moving the sample solution to a position over/under an optical fiber system and then capable of directing an input optical beam at said sensor and receiving an output optical beam from said sensor; and

said interrogation system capable of moving the reference solution to a position over/under an optical fiber system and then capable of directing an input optical beam at said sensor and receiving an output optical beam from said sensor; and

said interrogation system includes an optical detection system for receiving the output light from the optical fiber and converting it to an electrical form, for both the sample and reference solutions; and

a computer for analyzing the output signals received by said interrogation system to determine a detection signal associated with the sample solution flowing in a detection region of the sensing region of said sensor and to determine a reference signal associated with the reference solution flowing in a reference region of the sensing region of said sensor; and

said computer for subtracting the reference signal from the detection signal so as to generate a corrected detection signal which indicates whether or not a biomolecular binding event occurred in the sample solution flowing in said micron-sized deep flow channel.

41. The interrogation system of claim 40, wherein said interrogation system is an angular interrogation system.

42. The interrogation system of claim 40, wherein said interrogation system is a spectral interrogation system.