Methods for conducting tests

• US 6,300,138 B1
• Filed: 03/18/1999
• Issued: 10/09/2001
• Est. Priority Date: 08/01/1997
• Status: Expired due to Term

• Current Assignee: Qualigen, Inc.
• Original Assignee: Qualigen, Inc.
• Inventors: Mahant, Vijay K., Miller, Robert D, Bare, Rex O, Gleason, Paul J, Feistel, Christopher C, Walker, Glenn D.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US09/272,234
• Time in Patent Office: 936 Days
• Field of Search: 422/56, 422/58, 422/61, 422/100, 422/102, 422/103, 436/164, 436/165, 436/176, 436/177, 436/179, 436/180, 436/166, 436/808
• US Class Current: 436/165
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/505 flexible containers not provided for above
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/25625 Dilution

Abstract

Methods and apparatus for automated sample analysis are provided in which a plurality actuators are involved in moving a samples from one compartment to another, and appropriate reactants are combined with the sample in one or more of the compartments. The actuators are preferably contained in a device that also has a detector, data reduction capabilities, and a printer. Contemplated signal detectors include a photomultiplier tube, a photodiode, and a charge-coupled device. Steps contemplated to be performed automatically include aliquoting the sample, diluting the sample, contacting at least a portion of the sample with a reagent having a substantially selective binding towards the analyte. Contemplated reactants include sense and antisense nucleic acids, antibodies and antigens, solid-phases such as paramagnetic beads, reagents, other substrates, and wash solutions.

Claims

1. A method of testing a sample for a analyte, comprising:

providing a container having a plurality of fluidly discontinuous compartments, including a sample reacting compartent, different first and second reagents contained in first and second reagent compartments, respectively, and a signal detection compartment;

receiving the sample into the sample reacting compartment;

contacting a surface of the container with a device having a plurality of actuators;

operating multiple different sets of the actuators to independently add the first and second reagents to the sample in a variable sequence and time delay;

moving at least a portion of the reacted sample between the sample reacting compartment and the sample detection compartment using at least one of the sets of actuators; and

reading an analyte-dependent signal from the reacted sample contained in the sample detection compartment.

2. The method of claim 1, wherein the container has a flexible top sheet and a flexible bottom sheet, and wherein at least one of the compartments is formed by the flexible top sheet and bottom sheet.

3. The method of claim 1, further comprising aliquoting the sample.

4. The method of claim 1, wherein the step of receiving the sample comprises diluting the sample.

5. The method of claim 1, wherein the step of operating the actuators comprises contacting at least a portion of the sample with a composition having a substantially selective binding towards the analyte.

6. The method of claim 1, wherein the step of operating the actuators comprises contacting at least a portion of the sample with a composition selected from the group consisting of nucleic acids, antibodies, antigens, solid-phases, substrates, wash solutions, and buffers.

7. The method of claim 1, wherein the step of operating the actuators comprises aliquoting the sample, contacting at least a portion of the sample with a composition having a substantially selective binding towards the analyte, and contacting at least a portion of the sample with a reagent selected from the group consisting of a solid-phase, a wash solution, and a substrate.

8. The method of claim 1, wherein at least a portion of the sample is reversibly moved between the sample reacting compartment and the sample detecting compartment.

9. The method of claim 1, further comprising receiving the sample into a sample receiving compartment distinct form the sample reacting compartment.

10. The method of claim 1, wherein the fit and second reagents can be added to the sample in any variable sequence.

11. The method of claim 1, wherein the first reagent is selected from the group consisting of antibody, nucleic acids, chromophore, and amplifier.

12. The method of claim 1, wherein at least one of the actuators comprises a compression pad.

13. The method of any of claims 1-12, further comprising providing the device with a signal detector, and detecting the signal using the signal detector.

14. The method of claim 13, wherein detecting the signal using the signal detector comprises detecting multiple events separated by at least one minute.

15. The method of claim 13, wherein detecting the signal is performed at more than one of the compartments.

16. The method of claim 13, wherein the signal detector is selected from the group consisting of a photomultiplier tube, a photodiode, and a charge-coupled device.

17. The method of any of claims 1-12, further comprising the device calculating a result using the signal.

18. The method of any of claims 1-12, further comprising providing the device with an onboard printer, and printing an output relating to the result.

19. The method of any of claims 1-12, further comprising providing the device with an electronic interface to an external device, and sending an output relating to the result through the interface.

20. The method of any of claims 1-12, further comprising washing the sample, with a waste fluid passing into a waste compartment.

21. The method of claim 1 wherein the signal is dependent on the concentration of the analyte.

22. The method of claim 1 wherein the step of reacting further comprises washing complex formed between the analyte and at least one of the first reagent and second reagents.