Excitable target marker detection

• US 7,604,981 B1
• Filed: 03/07/2003
• Issued: 10/20/2009
• Est. Priority Date: 03/08/2002
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Thrush, Evan P., Levi, Ofer, Harris, James S. Jr., Smith, Stephen J.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): TURK, NEIL N
• Application Number:
  US10/384,166
• Time in Patent Office: 2,419 Days
• Field of Search: 422/82.05, 422/50, 422 55- 58, 436/164, 436/165, 435/287.2
• US Class Current: 435/287.2
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6454 using an integrated detector array

Abstract

A variety of types of molecules are detected and/or analyzed using an integrated micro-circuit arrangement. According to an example embodiment of the present invention, a micro-circuit arrangement detects excitable target markers in response to an excitation source. The excitation source emits a first electromagnetic radiation to excite one or more target markers into emitting a second electromagnetic radiation. The excitation source and detector combination can be optimized to detect a specific characteristic of a biological specimen. In this manner, an excitation source can be combined with several optical-detectors or detection channels, where each optical-detector is measuring or sensing the same or different characteristic of the biological specimen.

Claims

1. An array of micro-circuit arrangements for detecting excitable target markers located in an external medium, the array comprising:

a foundation layer having a first surface; and

a plurality of micro-circuit arrangements coupled to the first surface in proximity to one another and arranged in an array, each micro-circuit arrangement including;

an excitation source coupled to the first surface, and adapted to emit a first respective electromagnetic radiation in a direction predominately away from the foundation layer to excite a respective target marker into emitting a second respective electromagnetic radiation;

at least one corresponding optical-detector coupled to the first surface in proximity to the excitation source and arranged in the array with the excitation source, the at least one corresponding optical-detector adapted to sense the second respective electromagnetic radiation from a second direction opposite the first direction and generate a respective detection signal responsive to sensing the respective second electromagnetic radiation; and

a filter optically coupled to the at least one corresponding optical-detector, the filter being arranged and configured to attenuate the first respective electromagnetic radiation from being sensed by the at least one corresponding optical-detector;

wherein first and second groups of the plurality of micro-circuit arrangements are configured differently based on at least one of;

ability to sense fluorescence decay of the target marker at first and second times, respectively; and

different filter responses provided respectively by the first and second groups of the plurality of micro-circuit arrangements.

2. The array of claim 1, wherein each of the at least one corresponding optical detectors are adapted to sense a common second electromagnetic radiation.

3. The array of claim 2, wherein one portion of the plurality of micro-circuit arrangements is adapted to sense a particular characteristic of the common second corresponding electromagnetic radiation, and another portion of the plurality of micro-circuit arrangements are adapted to sense a different particular characteristic of the common second corresponding electromagnetic radiation.

4. The array of claim 3, wherein the plurality of micro-circuit arrangements are configured and arranged to sequentially present a target marker as the respective target marker to a portion of the plurality of micro-circuit arrangements.

7. The array of claim 1, wherein the second respective electromagnetic radiation excited and sensed by a portion of the plurality of micro-circuit arrangements has different characteristics from the second respective electromagnetic radiation excited and sensed by another portion of the plurality of micro-circuit arrangements.

8. The array of claim 1, wherein a portion of the plurality of micro-circuit arrangements includes corresponding optical detectors that are adapted to sense a second respective electromagnetic radiation having different characteristics from the second respective electromagnetic radiation sensed by corresponding optical detectors included in another portion of the plurality of micro-circuit arrangements.

9. The array of claim 1, wherein a portion of the plurality of micro-circuit arrangements includes filters having a different filter response from the filter response of filters included in another portion of the plurality of micro-circuit arrangements.

10. The array of claim 1, wherein at least a portion of the plurality of micro-circuit arrangements is arranged in a channel through which particles flow and adapted to detect a molecular flowrate of particles through the channel.

5. An array of micro-circuit arrangements for detecting excitable target markers located in an external medium, the array comprising:

a foundation layer having a first surface; and

a plurality of micro-circuit arrangements coupled to the first surface in proximity to one another and arranged in an array, each micro-circuit arrangement including;

an excitation source coupled to the first surface, and adapted to emit a first respective electromagnetic radiation in a direction predominately away from the foundation layer to excite a respective target marker into emitting a second respective electromagnetic radiation;

at least one corresponding optical-detector coupled to the first surface in proximity to the excitation source and arranged in the array with the excitation source, the at least one corresponding optical-detector adapted to sense the second respective electromagnetic radiation from a second direction opposite the first direction and generate a respective detection signal responsive to sensing the respective second electromagnetic radiation; and

a filter optically coupled to the at least one corresponding optical-detector, the filter being arranged and configured to attenuate the first respective electromagnetic radiation from being sensed by the at least one corresponding optical-detector, wherein one portion of the plurality of micro-circuit arrangements are configured to sense fluorescence decay of the target marker at a first time, and another portion of the plurality of micro-circuit arrangements are configured to sense fluorescence decay of the target marker at a second time.

6. The array of claim 5, further comprising a target marker detection channel structure adapted to pass the target marker sequentially between portions of the plurality of micro-circuit arrangements over time.