Silicon semiconductor wafer for analyzing micronic biological samples

• US 4,908,112 A
• Filed: 06/16/1988
• Issued: 03/13/1990
• Est. Priority Date: 06/16/1988
• Status: Expired due to Term

• Current Assignee: Dade Behring, Inc. (Siemens AG)
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Pace, Salvatore J.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Rodriguez, Isabelle
• Application Number:
  US07/207,535
• Time in Patent Office: 635 Days
• Field of Search: 204/299 R, 356/344, 356/318, 250/461.2
• US Class Current: 210/198.2
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 2030/162 electromigration
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 27/44721 by optical means
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44773 Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: G01N 30/16 Injection G01N30/24 takes precedence
• CPC Class Codes: G01N 30/6052 body
• CPC Class Codes: G01N 30/6082 transparent to radiation
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J

Abstract

An analytical separation device in which a capillary sized conduit is formed by a channel in a semiconductor device and the channel is closed by a glass plate. Electrodes are positioned in the channel and to activate the motion of liquids through the conduit by electroosmosis.

Claims

1. An improved separation device, comprising a capillary sized, closed conduit adapted to be filled with liquid or solid materials for electrophoretic and/or chromatographic separations, means to introduce a sample to be processed into the conduit, the device characterized by

a semiconductor slab having a channel in one face and a cover plate attached to the one slab to form the closed conduit, adapted to receive an ionizable liquid, and means for applying an electric potential along the length of the interior of the conduit.

2. The device set forth in claim 1 further characterized by the conduit being rectangular, ellipsoidal, triangular, or trapezoidal in cross-section, the slab being silicon, and the plate being glass, at least one interior dimension transverse to the conduit being less than 100 μ

.

3. The device set forth in claim 1 further characterized by the conduit having a rectangular cross-section with height and width dimensions, the height to width aspect ratio of the conduit being greater than 10:

1.

4. The device set forth in claim 2 wherein the means for applying a potential comprises at least one electrode disposed in the channel on the slab and at least one electrode disposed in a reservoir.

5. The device set forth in claim 4 further characterized by the slab and cover plate defining a reservoir at each end of the channel.

6. The device set forth in claim 4 further characterized by the slab and cover plate defining a second conduit intersecting with the first conduit.

7. The device set forth in claim 6 further characterized by a detector associated with the conduit adapted to detect any sample passing through the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely of and through the interior of the conduit, the photodetector positioned to view the conduit.

8. The device set forth in claim 2 wherein the means for applying a potential comprises at least one electrode disposed in the channel on the slab and at least one electrode disposed in one reservoir, and means to vary the electrical potential of each such electrode to control the flow of the ionizable liquid by electroosmosis.

9. The device set forth in claim 8 further characterized by the slab and cover plate defining a second conduit intersecting with the first conduit.

10. The device set forth in claim 9 further characterized by a detector positioned to recognize particles of interest in ionizable liquid of at least one point in the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely of and through the interior of the conduit.

11. The device set forth in claim 3 wherein the means for applying a potential comprises at least one electrode disposed in the channel on the slab and at least one electrode disposed in a reservoir, and means to vary the electrical potential of each such electrode to control he electroosmatic flow of the ionizable liquid by electro-osmosis.

12. The device set forth in claim 11 further characterized by the slab and cover plate defining a second conduit intersecting with the first conduit.

13. The device set forth in claim 12 further characterized by a detector associated with the conduit adapted to detect the ionizable liquid exiting the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely of and through the interior of the conduit.

14. The device set forth in claim 2 further characterized by a detector associated with the conduit to detect the ionizable liquid exiting the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely of said through the interior of the conduit, the photo detector positioned to view the conduit.

15. The device set forth in claim 1 further characterized by the depth to width aspect ratio of the interior of the conduit is greater than 1.

16. An improved gel electrophoresis device with a first conduit having an inlet and an outlet, the conduit being filled with an electrophoretic gel, means for applying an electric potential along the length of the interior of the conduit inlet, and a detector positioned along the conduit, the device characterized by

all dimensions transverse to the conduit being greater than 100 μ

m, and

the conduit being defined by a silicon slab having a channel in one face and a cover plate attached to the one slab face to form the conduit.

17. The device set forth in claim 16 further characterized by the means for applying a potential comprising at least one electrode in the channel of the slab and at least one electrode in a reservoir, and means to adjust independently the electrical potential of each electrode to control the migration rate of the electrically charged sample molecules.

18. The device set forth in claim 16 wherein the sample includes a fluorescing dye and the device is further characterized by the detector being positioned to recognize particles of interest in a sample at least one point in the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely through the interior of the conduit to provide such energy that will cause excitation of the fluorescing dye molecules attached to the electrically charged molecules.

19. The device set forth in claim 17 further characterized by the conduit being trapezoidal in cross-section, with the sides of the trapezoid forming 54.7°

exterior angles with the base, the laser beam being directed through the plate to one side to be reflected through the conduit and back out of the conduit by the second side and the plate to the photo detector.

20. The device set forth in claim 16 wherein the sample includes a fluorescing dye and the device is further characterized by a detector system being positioned to recognize particles of interest in a sample at least one point in the conduit, the detector having a laser and a photo detector, the laser beam being directed transversely through the interior of the conduit to provide such energy that will cause excitation of the fluorescing dye molecules attached to the electrically charged molecules.

21. The device set forth in claim 16 further characterized by the means for applying a potential comprising at least one electrode disposed in the channel of the slab and at least one electrode in a reservoir, and means to adjust independently the electrical potential of each electrode to control the migration rate of the electrically charged sample molecules.

22. The device set forth in claim 18 further characterized by the means to introduce a sample comprises a second channel formed by the slab and plate defining an inlet conduit connected to the first conduit, the inlet conduit having electrodes disposed therein in the channel, and means to vary the electrical potential of each electrode to direct the sample from the inlet conduit to the first conduit.

23. The device set forth in claim 16 further characterized by the means to introduce a sample comprises a second channel formed by the slab and plate defining an inlet conduit connected to the first conduit, the inlet conduit having electrodes disposed therein in the channel, and means to vary the electrical potential of each electrode to direct the sample from the inlet conduit to the first conduit.