Container for carrying out and monitoring biological processes

• US 7,273,749 B1
• Filed: 08/03/2000
• Issued: 09/25/2007
• Est. Priority Date: 06/04/1990
• Status: Expired due to Fees

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Wittwer, Carl T., Ririe, Kirk M.
• Primary Examiner(s): Beisner; William H
• Application Number:
  US09/631,339
• Time in Patent Office: 2,609 Days
• Field of Search: 435/288.1, 435/288.2, 435/287.2, 435/288.7, 4353041-3043, 435/307.1, 435/303.1, 422/72, 422/73, 422/100, 422/102, 422/914, 422/918, 422/923, 422/924, 356/246, 738/640.1, 738/640.2
• US Class Current: 435/287.2
• CPC Class Codes: B01D 15/34 Size selective separation, e.g. size exclusion chromatography, gel filtration, permeation
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 3/5082 Test tubes per se
• 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 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6823 Release of bound markers
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2527/107 Temperature of melting, i.e. Tm
• CPC Class Codes: C12Q 2531/113 PCR
• CPC Class Codes: C12Q 2561/113 Real time assay
• CPC Class Codes: C12Q 2565/101 Interaction between at least two labels
• CPC Class Codes: G01N 2021/6482 Sample cells, cuvettes
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/07 Centrifugal type cuvettes G01N21/09 takes precedence
• 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: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/06 : Preparation
• CPC Class Codes: G01N 30/466 : with separation columns in parallel
• CPC Class Codes: G01N 35/025 : having a carousel or turntable for reaction cells or cuvettes
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 435/809 : Incubators or racks or holders for culture plates or containers

Abstract

A thermal cycling method and device is disclosed. The device comprises a sample chamber whose temperature can be rapidly and accurately modulated over a range of temperatures needed to carry out a number of biological procedures, such as the DNA polymerase chain reaction. Biological samples are placed in containers each comprising a reservoir and a reaction portion, wherein the reaction portion has a small volume. The small volume reaction portion permits the rapid and accurate temperature modulation. With an optically transmissible reaction portion, DNA amplification may be monitored by fluorescence during PCR.

Claims

1. A container for holding a fluidic biological sample while undergoing nucleic acid amplification, the container consisting of:

a receiving portion having a first volume, the receiving portion being adapted to receive the biological sample therein; and

a reaction portion consisting of a capillary tube that is closed at one end, has an inner diameter selected from the range of about 0.25 mm to about 1.0 mm, and a capillary tube wall about 0.1 mm thick, said reaction portion being in fluidic communication with the receiving portion such that the biological sample placed in the receiving portion can travel to the reaction portion, the reaction portion having an internal volume not greater than a second volume, the second volume being less than the first volume and not greater than 1 milliliter, said reaction portion comprised of material having a thermal conductivity in the range from about 20 to about 35 in accordance with the formula;

2. A container as defined in claim 1 wherein the receiving portion is formed from a plastic material.

3. A container as defined in claim 2 wherein the receiving portion is in the shape of a funnel structure.

4. A container as defined in claim 1 wherein the capillary tube is a glass-capillary tube having an inner diameter of about 0.8 mm and an outer diameter of about 1.0 mm and the second volume is not greater than about 10 μ

l.

5. A container as defined in claim 1 wherein at least a portion of the reaction portion is transparent.

6. The container of claim 1 wherein the second volume is between about 0.01 μ

l to about 100 μ

l.

7. The container of claim 1 wherein the reaction portion comprises a glass capillary tube having a 0.8 mm inner diameter and a 1.0 mm outer diameter.

8. The container of claim 7 wherein the receiving portion is in the shape of a funnel and the capillary tube comprises a closed first end and a flared second end, the flared second end for receiving the funnel shaped portion of the receiving portion.

9. The container of claim 8 wherein the closed first end comprises a flat tip.

10. A container as defined in claim 9 wherein the capillary tube has a length of about 80 mm.

11. The container of claim 1 wherein the reaction portion has a volume to surface ratio of less than 0.25 mm.

12. The container of claim 1 wherein the closed end is formed to optimize optical transmissibility for light having a wavelength of about 400 nm to about 800 nm.

13. A container for holding a fluidic biological sample while undergoing nucleic acid amplification, the container consisting of:

a receiving portion having a first volume, the receiving portion being adapted to receive the biological sample therein; and

a reaction portion consisting of a capillary tube that is closed at one end, has an inner diameter in the range from about 0.02 mm to about 0.1 mm, and a capillary tube wall about 0.1 mm thick, said reaction portion being in fluidic communication with the receiving portion such that the biological sample placed in the receiving portion can travel to the reaction portion, the reaction portion having an internal volume not greater than a second volume, the second volume being less than the first volume and not greater than 1 milliliter, said reaction portion comprised of material having a thermal conductivity in the range from about 20 to about 35 in accordance with the formula;

14. A container for rapidly heating and cooling a fluidic biological sample contained therein, the container consisting of:

a receiving portion defining a first internal volume, the receiving portion being adapted to receive the biological sample therein;

a reaction portion, consisting of a thin walled capillary tube that is closed at one end, and has an inner diameter selected from the range of about 0.25 mm to about 1.0 mm, wherein the closed end is formed for optical transmissibility through the closed end, and the capillary tube wall is about 0.1 mm thick or less, said reaction portion being in fluidic communication with the receiving portion such that the biological sample placed in the receiving portion can travel to the reaction portion, the reaction portion having an internal volume not greater than a second volume, the second volume being less than the first volume and not greater than 100 μ

l.

15. The container of claim 14 wherein the receiving portion is in the shape of a funnel structure.

16. The container of claim 14 wherein the reaction portion comprises a glass capillary tube having a 0.8 mm inner diameter and a 1.0 mm outer diameter.

17. The container of claim 14 wherein the closed end comprises a flat tip.