Molecular reader

• US 8,449,842 B2
• Filed: 03/11/2010
• Issued: 05/28/2013
• Est. Priority Date: 03/19/2009
• Status: Active Grant

• Current Assignee: Thermo Scientific Portable Analytical Instruments Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Thermo Scientific Portable Analytical Instruments Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Knopp, Kevin J., Vakhshoori, Daryoosh, Wang, Peidong, Azimi, Masud, Miller, Scott E., Goldstein, Jason, McLaughlin, Stephen
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US12/722,211
• Publication Number:
  US 20110022324A1
• Time in Patent Office: 1,174 Days
• Field of Search: 422/50, 422500-502, 422/566, 422/536, 436/180, 204/452
• US Class Current: 422/536
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

Systems and methods disclosed include: a support apparatus configured to detachably receive a chip; movable pins extendible from a first position to a second position, where, in the first position, the movable pins do not contact a chip positioned on the support apparatus, and in the second position, the movable pins contact electrical terminals of a heating element within a chip positioned on the support apparatus; a radiation source configured to direct radiation to be incident on a chip positioned on the support apparatus; a detector; and an electronic processor, the electronic processor being configured to detect molecules in a sample positioned within the chip, and to determine a temperature of the chip by measuring an electrical resistance between two of the multiple pins connected to the electrical terminals.

Claims

1. A system, comprising:

a support apparatus configured to detachably receive a chip;

a plurality of movable pins extendible from a first position to a second position, wherein;

in the first position, the movable pins do not contact the chip when the chip is positioned on the support apparatus; and

in the second position, the movable pins contact electrical terminals of a heating element within the chip when the chip is positioned on the support apparatus;

a radiation source configured to direct radiation to be incident on the chip when the chip is positioned on the support apparatus;

a detector configured to detect radiation emitted from the chip when the chip is positioned on the support apparatus; and

an electronic processor in electrical communication with the plurality of movable pins and the detector, wherein the electronic processor is configured to detect molecules in a sample positioned within the chip by analyzing the detected radiation, and to determine a temperature of the chip by measuring an electrical resistance between two of the multiple pins connected to the electrical terminals.

2. The system of claim 1, wherein the electronic processor is configured to cause at least some of the plurality of movable pins to extend from the first position to the second position when the chip is received by the support apparatus.

3. The system of claim 1, wherein the electronic processor is configured to control the temperature of a localized area of the chip by applying an electrical potential difference between the electrical terminals.

4. The system of claim 1, further comprising a movable vacuum source extendible from a first vacuum position not in contact with the chip to a second vacuum position in contact with the chip when the chip is positioned on the support apparatus.

5. The system of claim 4, wherein the electronic processor is configured to extend the vacuum source from the first vacuum position to the second vacuum position to form a fluid connection with a channel positioned in the chip.

6. The system of claim 1, further comprising at least one extendible member electrically connected to the electronic processor and positioned so that when the chip is received by the support apparatus, the at least one extendible member contacts the chip and extends to deform a wall of a channel formed within the chip.

7. The system of claim 6, wherein the electronic processor controls movement of the at least one extendible member between a first position where the at least one extendible member applies a first pressure to the channel wall, and a second position where the at least one extendible member applies a second pressure different from the first pressure to the channel wall, and wherein the electronic processor controls an open cross-sectional area of the channel by controlling the extension of the at least one extendible member.

8. The system of claim 1, wherein the detector is configured to acquire an image of the chip when the chip is received by the support apparatus, and wherein the electronic processor is configured to determine the position of the chip and whether the chip is positioned correctly based on the image.

9. The system of claim 1, further comprising a housing that encloses the support apparatus, the plurality of movable pins, the radiation source, the detector, and the electronic processor, the housing having an opening through which the chip can be received by the support apparatus, and a closing member adjustable between an open position wherein the opening is at least partially unobstructed by the closing member and a closed position wherein the closing member seals the opening.

10. The system of claim 9, wherein the closing member is mechanically coupled to at least some of the plurality of movable pins so that when the closing member is moved from the open position to the closed position, the at least some of the plurality of movable pins are moved from the first position to the second position.

11. The system of claim 1, wherein the electronic processor is configured to detect at least one of molecules comprising amino acids and molecules comprising nucleic acids in a sample positioned within the chip.

12. The system of claim 1, further comprising a communications interface, wherein the electronic processor is configured to transmit data to, and receive data from, one or more external devices through the communications interface.

13. The system of claim 12, wherein the communications interface comprises a wireless transmitter and receiver electrically coupled to the electronic processor and configured to transmit and receive electronic signals.

14. A system, comprising:

a support apparatus configured to detachably receive a chip;

at least one extendible member positioned so that when the chip is received by the support apparatus, the at least one extendible member contacts the chip in a first member position and extends to deform a wall of a channel formed within the chip in a second member position;

a radiation source configured to direct radiation to be incident on the chip when the chip is positioned on the support apparatus;

a detector configured to detect radiation emitted from the chip when the chip is positioned on the support apparatus; and

an electronic processor in electrical communication with the at least one extendible member and the detector,

wherein the electronic processor is configured to detect molecules in a sample positioned within the chip by analyzing the detected radiation; and

wherein the electronic processor is configured to regulate a flow of fluid through the channel by controlling an extension of the at least one extendible member.

15. The system of claim 14, further comprising a plurality of movable pins extendible from a first position to a second position, wherein:

in the first position, the movable pins do not contact the chip when the chip is positioned on the support apparatus; and

in the second position, the movable pins contact electrical terminals of a heating element within the chip when the chip is positioned on the support apparatus; and

wherein the electronic processor is in electrical communication with the plurality of movable pins.

16. The system of claim 15, wherein the electronic processor is configured to cause at least some of the plurality of movable pins to extend from the first position to the second position when the chip is received by the support apparatus.

17. The system of claim 15, further comprising:

a housing that encloses the support apparatus, the plurality of movable pins, the at least one extendible member, the radiation source, the detector, and the electronic processor, the housing having an opening through which the chip can be received by the support apparatus, and a closing member adjustable between an open position wherein the opening is at least partially unobstructed by the closing member and a closed position wherein the closing member seals the opening, and

wherein the closing member is mechanically coupled to at least some of the plurality of movable pins so that when the closing member is moved from the open position to the closed position, the at least some of the plurality of movable pins are moved from the first position to the second position.

18. The system of claim 14, further comprising a movable vacuum source extendible from a first vacuum position not in contact with the chip to a second vacuum position in contact with the chip when the chip is positioned on the support apparatus, and wherein the electronic processor is configured to extend the vacuum source from the first vacuum position to the second vacuum position to form a fluid connection with a vacuum channel positioned in the chip.

19. The system of claim 14, wherein the at least one extendible member comprises a motorized actuator coupled to the electronic processor.

20. The system of claim 19, wherein the motorized actuator comprises a shaft coupled to a rotatable disc comprising at least one pin, and wherein the at least one pin deforms the wall of the channel.

21. The system of claim 19, wherein the motorized actuator comprises at least one pin coupled to a spring, and the actuator further comprises a rotating camshaft that controls an extension of the at least one pin.

22. The system of claim 14, wherein the electronic processor controls movement of the at least one extendible member between the first member position where the at least one extendible member applies a first pressure to the channel wall, and the second member position where the at least one extendible member applies a second pressure different from the first pressure to the channel wall.

23. The system of claim 14, further comprising a housing that encloses the support apparatus, the at least one extendible member, the radiation source, the detector, and the electronic processor, the housing having an opening through which the chip can be received by the support apparatus, and a closing member adjustable between an open position wherein the opening is at least partially unobstructed by the closing member and a closed position wherein the closing member seals the opening.

24. A method, comprising:

positioning a chip on a support stage configured to detachably receive the chip;

extending a plurality of movable pins from a first position not in contact with the chip to a second position wherein the movable pins contact electrical terminals of a heating element within the chip;

directing illumination radiation to be incident on the chip;

measuring radiation emitted from the chip; and

detecting molecules in a sample positioned within the chip based on the measured radiation.

25. The method of claim 24, further comprising one of measuring a temperature of the chip and controlling a temperature of the chip by applying an electrical potential difference between the electrical terminals.

26. The method of claim 24, further comprising positioning a vacuum source into fluid communication with a vacuum channel formed in the chip.

27. The method of claim 24, further comprising, prior to extending the plurality of movable pins, measuring an image of the chip on the support stage and determining a position of the chip relative to the stage based on the image.

28. A method, comprising:

positioning a chip on a support stage configured to detachably receive the chip;

positioning an extendible member at a first member position so that the member contacts a wall of a channel formed in the chip;

regulating a flow of fluid through the channel by extending the extendible member to a second member position to control a cross-sectional shape of the channel;

directing illumination radiation to be incident on the chip;

measuring radiation emitted from the chip; and

detecting molecules in a sample positioned within the chip based on the measured radiation.

29. The method of claim 28, further comprising extending a plurality of movable pins from a first position not in contact with the chip to a second position wherein the movable pins contact electrical terminals of a heating element within the chip.

30. The method of claim 29, further comprising at least one of measuring a temperature of the chip and controlling a temperature of the chip by applying an electrical potential difference between the electrical terminals.

31. The method of claim 28, further comprising positioning a vacuum source into fluid communication with a vacuum channel formed in the chip.

32. The method of claim 28, further comprising, prior to positioning the extendible member, measuring an image of the chip on the support stage and determining a position of the chip relative to the stage based on the image.

33. The method of claim 28, wherein the molecules in the sample are detected based on a measurement of emitted radiation at one central wavelength.

34. The method of claim 28, wherein detecting molecules in the sample comprises detecting both molecules comprising amino acids and molecules comprising nucleic acids in the sample.