Systems and Methods for Multiple Analyte Detection

• US 20140162264A1
• Filed: 12/02/2013
• Published: 06/12/2014
• Est. Priority Date: 04/26/2005
• Status: Active Grant

• Current Assignee: Applied Biosystems, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Yue, Min, Liu, David M., Roy, Joy, Chiang, Yuh-Min, Yang, Joon Mo, Lehto, Dennis, Vann, Charles S., Beard, Nigel P., Harding, Ian A., Van Camp, John R., Dromaretsky, Alexander, Ermakov, Sergey V., Oldham, Mark F., Shariati, Maryam, Ulmanella, Umberto
• Granted Patent: US 9,714,444 B2
• Time in Patent Office: Days
• US Class Current: 435/6.11
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/048 enabling gas exchange, e.g. vents
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0694 vents used to stop and induce flow, backpressure valves
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Systems and methods for multiple analyte detection include a system for distribution of a biological sample that includes a substrate, wherein the substrate includes a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber. The system may further include a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate and a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber. The substrate can be constructed of detection-compatible and assay-compatible materials.

Claims

1. A system for distribution of a biological sample, the system comprising:

a substrate, wherein the substrate comprises a plurality of sample chambers, a sample introduction channel for each sample chamber, and a venting channel for each sample chamber;

a preloaded reagent contained in each sample chamber and configured for nucleic acid analysis of a biological sample that enters the substrate; and

a sealing instrument configured to be placed in contact with the substrate to seal each sample chamber so as to substantially prevent sample contained in each sample chamber from flowing out of each sample chamber,

wherein the substrate is constructed of detection-compatible and assay-compatible materials.

7. The system of claim 1, wherein the sealing plate is configured to be placed in contact with the substrate during a reaction process that occurs in the sample chambers to seal each sample chamber.

8. The system of claim 7, further comprising a thermal block, wherein the thermal block comprises the sealing plate.

9. The system of claim 1, wherein the sealing instrument comprises one of a plate and a roller.

10. The system of claim 1, wherein the substrate comprises a film layer and wherein a portion of the film layer fills the sample introduction channels and the venting channels upon contact of the sealing instrument with the substrate.

11. The system of claim 1, wherein the sealing instrument comprises a plurality of sealing protrusions.

12. The system of claim 11, wherein the sealing protrusions are configured to seal the sample introduction channels and venting channels for each sample chamber.

13. The system of claim 11, further comprising an additional sealing instrument, wherein the plurality of sealing protrusions comprises a first plurality of sealing protrusions associated with the sealing instrument and a second plurality of the sealing protrusions associated with the additional sealing instrument, the first plurality and second plurality of sealing protrusions being configured to seal differing groups of sample chambers when the sealing instrument and the additional sealing instrument are respectively placed in contact with the substrate.

14. The system of claim 13, wherein the first plurality of sealing protrusions is configured to seal the sample introduction channels for each sample chamber and the second plurality of sealing protrusions are configured to seal the venting channels for each sample chamber.

15. The system of claim 11, wherein each sealing protrusion is configured to contact a respective sample introduction channel and venting channel for each sample chamber when the sealing instrument is placed in contact with the substrate.

16. The system of claim 11, wherein the plurality of sealing protrusions are configured to respectively align with the plurality of sample chambers.

17. The system of claim 16, wherein each sample chamber is configured to receive a respective sealing protrusion such that the sealing protrusions seal the sealing chambers substantially at an inner peripheral surface defining each sample chamber.

18. The system of claim 11, wherein the sealing instrument further comprises a plurality of optical apertures configured to provide optical access to the sample chambers.

19. The system of claim 18, wherein the sealing protrusions are configured to pierce the substrate and enter the introduction and venting channels for each sample chamber.

20. The system of claim 11, wherein the sealing protrusions comprise one of pins, disks, blades, and bumps.

26. The system of claim 1, wherein the substrate further comprises a plurality of sample supply channels, each sample supply channel being in flow communication with a differing group of sample introduction channels and corresponding sample chambers.

27. The system of claim 26, wherein the substrate further comprises a plurality of sample inlet ports, each sample inlet port being in flow communication with a differing sample supply channel.

28. The system of claim 1, wherein the at least one venting mechanism comprises a plurality of venting mechanisms respectively corresponding to the plurality of sample chambers.

29. The system of claim 1, wherein the substrate further comprises a venting chamber in flow communication with each venting channel.

34. The system of claim 1, wherein the substrate further comprises a venting chamber for each sample chamber, the venting chambers being in flow communication with the sample chambers via the venting channels, wherein the at least one venting mechanism comprises a plurality of venting mechanisms each corresponding to a respective venting chamber.

35. The system of claim 1, wherein the substrate further comprises a main venting channel in flow communication with the venting channels.

44. The system of claim 1, wherein the substrate further comprises an additional film layer, the film layers being disposed on opposing surfaces of the base.

45. The system of claim 44, wherein the additional film layer and the base together define the sample chambers, sample introduction channels, and venting channels.

49. The system of claim 1, wherein the at least one venting mechanism is configured to substantially prevent sample from passing through the at least one venting mechanism and out of the substrate.

2-6. -6. (canceled)

21-25. -25. (canceled)

30-33. -33. (canceled)

36-43. -43. (canceled)

46-48. -48. (canceled)

50. A method for distribution of a biological sample, the method comprising:

providing a base, wherein the base comprises a plurality of sample cavities containing a preloaded reagent therein, a sample introduction trench for each sample cavity, and a venting trench for each sample cavity, and wherein the base is constructed of detection-compatible and assay-compatible materials;

providing a film to adhere to the base to form a substrate, wherein the film and base form a plurality of sample chambers from each sample cavity, a sample introduction channel from each sample introduction trench, and a venting channel from each sample venting trench;

supplying the biological sample to the substrate;

filling the sample chambers with the biological sample via the sample introduction channels;

passing gas out of the substrate via at least one venting mechanism in the substrate; and

sealing the sample chambers to substantially prevent sample in the sample chambers from flowing out of the sample chambers.

51. The method of claim 50, wherein the sealing the sample chambers comprises placing a sealing instrument in contact with the substrate.

52. The method of claim 50, wherein filling the sample chambers comprises at least one of spinning the substrate to provide centrifugal force, sizing the sample introductory channels to provide capillary force, and aspirating the sample through the vent channels.

53. The method of claim 50, wherein filling the sample chambers comprises providing positive pressure to the sample.

54. The method of claim 53, further comprising venting gas in the sample chamber through the venting channels and the at least one venting mechanism.

56. The method of claim 50, further comprising substantially preventing the sample from passing through the at least one venting mechanism and out of the substrate.

57. The method of claim 56, wherein preventing the sample from passing through the at least one venting mechanism comprises holding the sample in the venting mechanism via capillarity.

55. (canceled)

58. A system for distribution of a biological sample, the system comprising:

means for distributing the sample to a plurality of sample chambers containing a preloaded reagent;

means for venting each of the sample chambers; and

means for sealing each of the sample chambers.

59-65. -65. (canceled)