Assay system and method for conducting assays

• US 5,882,903 A
• Filed: 11/01/1996
• Issued: 03/16/1999
• Est. Priority Date: 11/01/1996
• Status: Expired due to Term

• Current Assignee: Sarnoff Corporation (SRI International, Inc.)
• Original Assignee: Sarnoff Corporation (SRI International, Inc.)
• Inventors: Zanzucchi, Peter John, Southgate, Peter David, Roach, William Ronald, Andrevski, Zygmunt M.
• Primary Examiner(s): Sisson, Bradley L.
• Application Number:
  US08/742,317
• Time in Patent Office: 865 Days
• Field of Search: 422/50, 422/55, 422/58, 422/62, 422/63, 422/64, 422/67, 422/68.1, 422/82.05, 422/82.12, 422/99, 435/286.5, 435/287.1, 435/287.2, 435/287.3, 935/85
• US Class Current: 435/91.2
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 2547/101 by confinement to a single tube/container

Abstract

The invention relates to an assay system for conducting elevated temperature reactions in a fluid-tight manner within a reaction chamber, the assay system comprising: (a) a first assembly comprising the reaction chamber, and (b) a second assembly for temperature control, wherein the second assembly can be positioned adjacent to the reaction chamber. More particularly, the invention relates to an assay system comprising (a) a reaction chamber having a cover formed of a deformable material and (b) a mechanism for rapidly adjusting the temperature of the reaction chamber.

Claims

1. An assay system for conducting elevated temperature reactions in a fluid-tight manner within an enclosed reaction chamber, the assay system comprising:

(a) a first assembly comprising the reaction chamber and a first fluid exchange channel that provides fluid communication to and from the reaction chamber, (b) a second assembly for temperature control, wherein the second assembly is positioned adjacent to the reaction chamber; and

(c) a third assembly that is slidably positioned in contact with the first assembly and contains a plurality of fluid chambers, wherein the first assembly fits within the third assembly in a fluid-tight, slidable manner such that fluid does not flow through the first fluid exchange channel when the first fluid exchange channel is not aligned with a fluid exchange channel in the third assembly, the fluid chambers having fluid exchange ports, a plurality of which fluid exchange ports can be aligned with the first fluid exchange channel by sidably positioning the third assembly relative to the first assembly, wherein a particular fluid chamber can be in fluid communication with the reaction chamber.

2. The assay system of claim 1, further comprising, positioned to interact with the third assembly, a first fluid impeller for impelling a fluid to flow from a fluid chamber having a fluid exchange port which can be aligned with the first fluid exchange channel into the reaction chamber of the aligned first fluid exchange channel.

3. The assay system of claim 2, further comprising a slider for sliding the third assembly or the first assembly and a processor for controlling:

(a) the sliding of the third assembly or the first assembly, and (b) the first fluid impeller.

4. The assay system of claim 3, wherein the slider effects linear or circular movement between the first and third assemblies.

5. The assay system of claim 2, wherein the second assembly comprises a heat source, and further comprising a magnet positioned adjacent to the reaction chamber, a rotator, on which the magnet is mounted, for rotating the magnet, a slider, operatively linked to the first or third assembly, for sliding the first or third assembly, and a processor for controlling:

(a) the sliding of the first assembly or the third assembly, (b) the first fluid impeller, (c) the heat source, and (d) the rotation of the magnet.

6. A method of conducting a PCR reaction comprising (a) introducing a sample into a first reaction chamber of the assay system of claim 2 and transferring from one or more fluid chambers to the first reaction chamber solutions containing reagents necessary for conducting the PCR reaction and (b) cycling the temperature to achieve cycles of nucleic acid amplification.

7. The method of claim 6, wherein the second assembly raises the temperature from about 25°

C. to about 75°

C. within about 5 seconds.

8. The method of claim 6, wherein the second assembly lowers the temperature from about 75°

C. to about 50°

C. within about 5 seconds.

9. The assay system of claim 1, further comprising, positioned to interact with the first assembly, a second fluid impeller for, when the fluid exchage port of a fluid chamber is aligned with the first fluid exchange channel, impelling a fluid to flow from the reaction chamber through the first fluid exchange channel and the aligned fluid exchange port into that fluid chamber.

10. The assay system of claim 1, wherein the fluid-tight seal between the first assembly and the third assembly is effective in retaining a fluid in the reaction chamber when the temperature of the fluid is at about 90°

C. to about 100°

C.

11. The assay system of claim 1, wherein at least one reaction or fluid chamber has an external transparent wall.

12. The assay system of claim 11, further comprising a light source capable of directing light to the external transparent wall of the reaction or fluid chamber.

13. The assay system of claim 12, further comprising a light detection device capable of detecting (a) the light reflected from an illuminated reaction or fluid chamber having the external transparent wall, (b) the light transmitted through an illuminated reaction or fluid chamber having the external transparent wall, or (c) the light emissions emanating from an excited molecule in a reaction or fluid chamber having the external transparent wall.

14. The assay system of claim 1, wherein the second assembly comprises a heat source, a cooling sink, or both.

15. The assay system of claim 14, further comprising a temperature monitoring device for monitoring the temperature of the reaction chamber operatively connected to the second assembly.

16. The assay system of claim 15, further comprising a processor for receiving a signal from the temperature monitoring device and for controlling the heat source operatively connected to the temperature monitoring device.

17. The assay system of claim 16, wherein the cooling sink is under the control of the processor.

18. The assay system of claim 17, wherein the cooling sink comprises conduits containing a circulating fluid and an impeller for causing said fluid to circulate.

19. The assay system of claim 1, wherein the first component comprises a plurality of reaction chambers, each having a fluid exchange channel.

20. The assay system of claim 19, wherein the first component comprises at least about 3 reaction chambers.

21. An system for conducting chemical assays having a mechanism for adjusting the temperature of a reaction chamber, the assay system comprising:

(a) a first assembly comprising an enclosed reaction chamber having a upper and a lower cover and a thickness defined by the distance between the upper and lower covers, wherein at least the upper cover is formed of a deformable material, (b) a second assembly comprising a heat source, a cooling sink, and a plurality of pressurized fluid channels that open on the surface of the second component assembly, wherein the second assembly is positioned adjacent to the reaction chamber, wherein the reaction chamber further comprises at least one sealable entry port and (c) a pressure controller operatively linked to the pressurized fluid channels, for controlling gas pressure within the pressurized fluid channels;

wherein the second assembly can be positioned adjacent to the reaction chamber such that the pressurized fluid channels are in contact with the upper cover of the reaction chamber, and wherein elevated gas pressure can be channeled through the pressurized fluid channels to impact the upper cover and thereby push the upper cover towards the lower cover so as to narrow the width of the reaction chamber.

22. The assay system of claim 21, wherein the heat source comprises at least one electrical heater attached to the second assembly.

23. The assay system of claim 21, wherein the cooling sink comprises a conduit for water or other fluid integral to the second assembly and a fluid impeller for causing fluid to flow through the conduit.

24. The assay system of claim 21, wherein the second assembly comprises:

(a) first and second end plates, wherein the first end plate can be positioned adjacent to the reaction chamber, and (b) a plurality of paired p-type and n-type semiconductor blocks positioned between the first and second end-plates and electrically connected in series to form a thermoelectric heat punp, wherein the heat pump pumps heat from the first end plate to the second end plate when a voltage with a first polarity is applied across the serially connected semiconductor blocks and from the second end to the first end plate when a voltage of the polarity opposite the first polarity is applied across the serially connected semiconductor blocks.

25. The assay system of claim 21, wherein the reaction chamber thickness is about 1 mm or less.

26. The assay system of claim 21, wherein, when the second component is positioned adjacent to the upper cover and when a fluid in the pressurized fluid channels of the upper assembly has reduced pressure, the first cover adheres to the second assembly.

27. The assay system of claim 26, further comprising a translocator for moving the second assembly away from the upper assembly, wherein when the first cover is adhered to the second assembly, the second assembly can be moved away from the first assembly.