Electrochemical detector integrated on microfabricated capillary electrophoresis chips

• US 5,906,723 A
• Filed: 08/26/1996
• Issued: 05/25/1999
• Est. Priority Date: 08/26/1996
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Lao, Kaiqin, Woolley, Adam T., Mathies, Richard A., Glazer, Alexander N.
• Primary Examiner(s): Warden, Robert
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US08/703,394
• Time in Patent Office: 1,002 Days
• Field of Search: 204/451, 204/452, 204/601, 204/603
• US Class Current: 204/603
• CPC Class Codes: G01N 27/4473 by electric means
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize

Abstract

A microfabricated capillary electrophoresis chip which includes an integral thin film electrochemical detector for detecting molecules separated in the capillary.

Claims

1. In a microfabricated capillary electrophoresis chip including a substrate with an elongated separation channel with conductive means at each end of the channel for applying a separation voltage along the channel, the improvement comprising an integrated electrochemical detector having a thin film working electrode extending into said separation channel at or near the very end of said separation channel where the working electrode is close to ground potential and has minimal influence from the high electrophoresis potentials, in order to detect current generated by molecules undergoing redox reaction as they migrate past the thin film electrode after they have migrated the length of the channel, the portion of said thin film electrode extending into said channel being very narrow to minimize the electrophoresis voltage gradient which it senses, and a reference electrode spaced from said working electrode.

2. A microfabricated capillary electrophoresis chip as in claim 1 in which the reference electrode is a narrow thin film electrode which extends into said channel towards and spaced from side working electrode to form a detection region therebetween within the electrophoresis channel or at or just beyond the end thereof.

3. A microfabricated capillary electrophoresis chip as in claim 2 in which said channel is from 1-500 μ

m wide, said narrow ends are from 1-500 μ

m wide and the spacing between the narrow ends is from 1-500 μ

m.

4. A microfabricated capillary electrophoresis chip as in claim 2 including thin film leads extending from said thin film working electrode and said conductive means at each end of the separation channel to the same edge of said chip.

5. A microfabricated capillary electrophoresis chip as in claim 1 in which said thin film working electrode is covered with an insulating film which extends to a point near the end of the electrode.

6. A microfabricated capillary electrophoresis chip as in claim 1 in which the channel at one end transitions to a larger volume portion and said thin film working electrode is placed in or near the transition to a larger volume.

7. A microfabricated capillary electrophoresis chip as in claim 1 including a plurality of pairs of spaced working electrodes disposed along said end of said channel to perform multiple electrochemical detection.

8. A microfabricated capillary electrophoresis chip including a substrate with an elongated separation channel and a cover plate mounted on said substrate to form, with said channel, a separation capillary comprising:

thin film conductive means at each end of said capillary for applying a separation voltage along said capillary, and

an electrochemical detector having a thin film working electrode near the very end of said channel where the working electrode is close to ground potential and has minimal influence from the high electrophoresis potentials, wherein the thin film working electrode is adapted to detect molecules undergoing redox reaction as they migrate past the thin film electrode, the portion of said thin film working electrode extending into said channel being narrow and near the end of said capillary to minimize the separation voltage gradient which is senses, and a reference electrode spaced from said working electrode.

9. A microfabricated capillary electrophoresis chip as in claim 8 in which the thin film reference electrode extends into said channel towards and spaced from said working electrode to form a detection region therebetween within the capillary.

10. A microfabricated capillary electrophoresis chip as in claim 8 in which said thin film working electrode is covered with an insulating film which extends to a point near the end of the electrode.

11. A microfabricated capillary electrophoresis chip as in claim 8 in which said channel is from 1-500 μ

m wide, said narrow ends are 1-500 μ

m wide and the spacing between the ends is from 1-500 μ

m.

12. A microfabricated capillary electrophoresis chip as in claim 8 in which the channel transitions to a larger volume channel portion and said thin film working electrode is placed less than 500 μ

m from the transition to a larger volume.

13. A microfabricated capillary electrophoresis chip as in claim 8 including a plurality of pairs of spaced working electrodes disposed along said end of said capillary to perform multiple electrochemical detection.

14. A microfabricated capillary electrophoresis chip as in claim 8 including thin film leads extending from said thin film working electrode and said conductive means to one edge of said chip.

15. A microfabricated capillary electrophoresis chip including an etched glass substrate with an elongated separation channel and an injection channel and a cover plate mounted on said substrate to form, with said channels a separation and injection capillary comprising:

thin film leads extending from the same edge of said chip to connect to the ends of the separation and injection channels,

an integrated electrochemical detector having a thin film working electrode extending from said one edge into said separation channel at or near the very end of said channel where the working electrode is close to ground potential and has minimal influence from the high electrophoresis potentials, in order to detect current generated by molecules undergoing redox reaction as they migrate past the thin film electrode after they have migrated the length of the channels, the portion of said thin film electrode extending into said channel being narrow to minimize the electrophoresis voltage gradient which it senses, and

a reference electrode spaced from said working electrode.

16. A microfabricated capillary electrophoresis chip as in claim 15 in which the reference electrode is a thin film electrode extending from said one edge with a narrow end extending into said channel towards and spaced from said working electrode to form a detection region therebetween.

17. A microfabricated capillary electrophoresis chip as in claim 16 in which said channel is from 1-500 μ

m wide, said narrow ends are from 1-500 μ

m wide and the spacing between the ends is from 1-500 μ

m.

18. A microfabricated capillary electrophoresis chip as in claim 15 in which the channel transitions to a wider channel portion and said thin film electrodes are closely spaced from said channel transition.