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

• US 8,021,613 B2
• Filed: 09/11/2007
• Issued: 09/20/2011
• Est. Priority Date: 11/18/2004
• Status: Expired due to Fees

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Quesada, Mark A., Mazumder, Prantik, Yuen, Po Ki, Fontaine, Norman H., Mozdy, Eric J.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): Turk; Neil N
• Application Number:
  US11/900,263
• Publication Number:
  US 20080063569A1
• Time in Patent Office: 1,470 Days
• Field of Search: None
• US Class Current: 422/68.1
• 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 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 single sensing region of said sensor, wherein the single sensing region is divided into a detection region and a reference region which are contiguous to one another and which are respectively interfaced with the sample solution and the reference solution that flow side-by-side to one another in a longitudinal direction within the micron-sized deep flow channel;

an interrogation system configured to direct an input optical beam at said sensor and receiving an output optical beam from said sensor;

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

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

said computer configured to subtract the reference signal from the detection signal to generate a corrected detection signal, wherein uncertainties in the detection signal due to environmental conditions are reduced in the corrected detection signal.

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

4. The system of claim 1, wherein said micron-sized deep flow channel and said sensor are incorporated within a H-well plate.

5. The system of claim 1, wherein said interrogation system is an angular interrogation system in which the input optical beam has a single wavelength and is delivered to said sensor and in which the output optical beam is received from said sensor at the camera which is an optical detector or a charge-coupled device camera.

6. The system of claim 1, wherein said interrogation system is a spectral interrogation system in which the input optical beam is a collimated optical beam containing a plurality of wavelengths and is delivered to said sensor and in which the output optical beam is received from said sensor at the camera which is a spectrograph.

7. The system of claim 1, wherein said micron-sized deep flow channel is configured to receive a plurality of concentration gradients in the sample solution at the same time and said computer is configured to analyze the output optical beam to determine a plurality of detection signals corresponding to said plurality of concentration gradients in the sample solution.

8. 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 single sensing region of said sensor, wherein the single sensing region is divided into a detection region and a reference region which are contiguous to one another and which are respectively interfaced with the sample solution and the reference solution that flow side-by-side to one another in a longitudinal direction within the micron-sized deep flow channel;

an interrogation system configured to direct an input optical beam at said sensor and receiving an output optical beam from said sensor;

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

a computer/electrical circuit configured to subtract the reference signal from the detection signal to generate a corrected detection signal, wherein uncertainties in the detection signal due to environmental conditions are reduced in the corrected detection signal.

9. The system of claim 8, 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.

10. The system of claim 8, wherein said sensor is a grating-coupled waveguide sensor or a surface plasmon resonance sensor.

11. The system of claim 8, wherein said micron-sized deep flow channel and said sensor are incorporated within a H-well plate.

12. The system of claim 8, said interrogation system is an angular interrogation system in which the input optical beam has a single wavelength and is delivered to said sensor and in which the output optical beam is received from said sensor at the camera which is an optical detector or a charge-coupled device camera.

13. The system of claim 8, wherein said interrogation system is a spectral interrogation system in which the input optical beam is a collimated optical beam containing a plurality of wavelengths and is delivered to said sensor and in which the output optical beam is received from said sensor at the camera which is a spectrograph.

14. The system of claim 8, wherein said micron-sized deep flow channel is configured to receive a plurality of concentration gradients in the sample solution at the same time and said computer/electrical circuit is configured to analyze the output optical beam to determine a plurality of detection signals corresponding to said plurality of concentration gradients in the sample solution.