Robotic microchannel bioanalytical instrument

• US 6,764,648 B1
• Filed: 04/20/2000
• Issued: 07/20/2004
• Est. Priority Date: 07/02/1998
• Status: Expired due to Term

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Amersham Biosciences (General Electric Company)
• Inventors: Jovanovich, Stevan B., Roach, David J., Loder, Robert T. Jr., Armstrong, Thomas M., Harris, Dennis W., Johnston, Richard F.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): QUAN, ELIZABETH S
• Application Number:
  US09/556,897
• Time in Patent Office: 1,552 Days
• Field of Search: 422/63, 422/65-66, 422/81, 422/82.01, 422/82.02, 422/82.05, 422/100, 422/104, 422/50-62, 422/64, 422/67-68, 422/99, 422/102, 422/103, 436/43, 436/44, 436/145, 436/194, 436/180, 436/45-54, 204/451, 204/601, 204/604, 204/606, 435/287.2, 435/288.5, 435/287.3
• US Class Current: 422/63
• CPC Class Codes: B01L 13/02 for receptacle or instruments
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: G01N 2035/00059 vacuum chucks
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/0437 Cleaning cuvettes or reaction vessels
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44743 Introducing samples
• CPC Class Codes: G01N 27/44782 of a plurality of samples
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/110833 Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A substrate with a plurality of microchannels is movably deployed with other movable objects that will load sample into the microchannels, stimulate molecular migration, read the results of the migration, remove and replace the substrate, and prepare for a new run. The other objects include a gripper for engaging and moving the substrate, an electrode array of fine wires suitable for fitting into the microchannels for electromigration, and a scanning detector for reading migration results. A sequence of automatic operations is established so that one substrate after another may be moved into position, loaded with sample, stimulated for molecular migration, read with a beam, and then removed and replaced with a fresh substrate.

Claims

1. A robotic instrument for microchannel chemical analysis of samples in microchannels on a microchip substrate, the substrate having a plurality of microchannels therein with inlet ports in fluid communication with the microchannels, the instrument comprising:

a first frame,

a first track having the first frame movably mounted thereon,

a second frame for holding a microtiter plate, said plate having a plurality of spaced apart wells whose positions are known,

a second track having the second frame movably mounted thereon,

a gantry spanning the first and second tracks at an elevation above the tracks, the gantry carrying a multifunctional device including a plurality of ganged pipettors and a vacuum line, the multifunctional device being horizontally movable on the gantry and vertically movable from the gantry towards and away from the first track and the second track such that said multifunctional device may be aligned to transfer liquid from a plurality of wells on the plate to a plurality of inlet ports on the substrate,

a plurality of motors arranged to provide motive power to the multifunctional device, the first frame, and the second framed; and

a substrate gripper movable to the first frame from other location.

2. The apparatus of claim 1 further including a motor controlling vertical and horizontal motion of the gripper.

3. The robotic instrument of claim 1 further comprising a plurality of electrode wires mounted on a platform above the first track that are insertable into inlet ports of the substrate.

4. The robotic instrument of claim 3 further comprising a circuit board mounted to said platform wherein said electrode wires extend perpendicularly from said circuit board of said platform.

5. The robotic instrument of claim 4 wherein said circuit board has:

a first electrode terminal in electrical communication with a first wire trace and sample terminals of said microchip substrate,

a second electrode terminal in electrical communication with a second wire trace and cathode terminals of said microchip substrate,

a third electrode terminal in electrical communication with a third wire trace and waste terminals of said microchip substrate, and

a fourth electrode terminal in electrical communication with a fourth wire trace and an anode terminal of said microchip substrate.

6. The apparatus of claim 5 further comprising a fifth electrode terminal in electrical communication with a fifth wire trace and a second set of sample terminals of said microchip substrate.

7. The robotic instrument of claim 1 further comprising a detector located on a platform above the first track.

8. The robotic instrument of claim 7 wherein said detector includes a scanning confocal laser microscope.

9. The robotic instrument of claim 1 further comprising a platform above the first track, said platform having a detector and a plurality of wires located on it.

10. The robotic instrument of claim 1 wherein said plurality of pipettors have a spacing between each pipettor that matches the spacing between each of the wells of said spaced apart wells.

11. The robotic instrument of claim 1 further comprising a tip guide wherein said plurality of pipettors have tips that are inserted through said tip guide.

12. The robotic instrument of claim 1 further comprising a pipettor assembly actuator.

13. The apparatus of claim 3 further comprising an electrode wire wash station on said first frame.

14. The apparatus of claim 1 further comprising optical and mechanical position sensors located on said first and second frames.

15. A robotic instrument for microchannel chemical analysis of samples in microchannels on a microchip substrate, the substrate having a plurality of microchannels therein with inlet ports in fluid communication with the microchannels, the instrument comprising:

a first frame,

a first track having the first frame movably mounted thereon,

a second frame for holding a microtiter plate, said plate having a plurality of spaced apart wells whose positions are known,

a second track having the second frame movably mounted thereon,

a gantry spanning the first and second tracks at an elevation above the tracks, the gantry carrying a multifunctional device including a plurality of ganged pipettors and a vacuum line, the multifunctional device being horizontally movable on the gantry and vertically movable from the gantry towards and away from the first track and the second track such that said multifunctional device may be aligned to transfer liquid from a plurality of wells on the plate to a plurality of inlet ports on the substrate,

a plurality of motors arranged to provide motive power to the multifunctional device, the first frame, and the second frame; and

a plurality of electrode wires mounted on a platform above the first track that are insertable into inlet ports on the substrate.

16. The apparatus of claim 15 further defined by a substrate gripper movable to the first frame from other locations, the gripper having a motor controlling vertical and horizontal motion.

17. The robotic instrument of claim 16 further comprising a circuit board mounted to said platform wherein said electrode wires extend perpendicularly from said circuit board of said platform.

18. The robotic instrument of claim 17 wherein said circuit board has:

a first electrode terminal in electrical communication with a first wire trace and sample terminals of said microchip substrate,

a second electrode terminal in electrical communication with a second wire trace and cathode terminals of said microchip substrate,

a third electrode terminal in electrical communication with a third wire trace and waste terminals of said microchip substrate, and

a fourth electrode terminal in electrical communication with a fourth wire trace and an anode terminal of said microchip substrate.

19. The apparatus of claim 18 further comprising a fifth electrode terminal in electrical communication with a fifth wire trace and a second set of sample terminals of said microchip substrate.

20. The robotic instrument of claim 15 further comprising a detector located on said platform above the first track.

21. The robotic instrument of claim 20 wherein said detector includes a scanning confocal laser microscope.

22. The robotic instrument of claim 15 wherein said plurality of pipettors have a spacing between each pipettor that matches the spacing between each of the wells of said spaced apart wells.

23. The robotic Instrument of claim 15 further comprising a tip guide wherein said plurality of pipettors have tips that are inserted through said tip guide.

24. The robotic instrument of claim 15 further comprising a pipettor assembly actuator.

25. The apparatus of claim 15 further comprising an electrode wire wash station on said first frame.

26. The apparatus of claim 15 further comprising optical and mechanical position sensors located on said first and second frames.