Thermal cycling apparatus and method

• US 9,428,800 B2
• Filed: 03/03/2014
• Issued: 08/30/2016
• Est. Priority Date: 12/20/2002
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Linton, John, Katz, Arrin, Brenan, Colin, Yoder, Karl, Hess, Robert, Madrone, Leila, Ellis, Robert, Kanigan, Tanya, Friesen, Kristine, Morrison, Thomas, Garcia, Javier
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US14/195,358
• Publication Number:
  US 20140179566A1
• Time in Patent Office: 911 Days
• Field of Search: 436/43, 436/86, 436164-166, 436/180, 436/805, 436171-172, 436/147, 435/6.12, 435/6.1, 435/6.11, 422/67, 422/68.1
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0609 Holders integrated in container to position an object
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1838 using fluid heat transfer medium
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• 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 1/6858 Allele-specific amplification
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/056 Laminated construction
• CPC Class Codes: G01N 2021/158 Eliminating condensation
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/15 : Preventing contamination of the components of the optical system or obstruction of the light path
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A system for holding at least one of sample and reagent for analysis. The system includes a pair of parallel covers, at least one of which is light transmissive, of which pair a light transmissive cover forms a top, and of which pair the other forms a bottom. A frame is disposed between the covers to define, in relation to the covers, an interior volume. The frame and the covers are associated with one another to form a case, the case being substantially tight to liquids. A microfluidic array is disposed in the interior volume. The array includes a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces, the through-holes containing at least one of sample and reagent.

Claims

1. A system for analyzing a PCR reaction, comprising:

a sample holder comprising a plurality of reaction volumes configured to receive a corresponding plurality of samples, each reaction volume having a volume of less than 100 nanoliters, the reaction volumes being spatially separated from one another;

a case comprising a case volume and an opening, the case configured to contain the sample holder within the case volume, the opening configured for dispensing a liquid into the case volume;

an imaging system comprising an illumination source, the imaging system configured to image the plurality of samples; and

a processor comprising analysis software configured to perform an end-point PCR analysis on at least some of the plurality of samples;

wherein the sample holder comprises a sheet of material comprising a pair of opposing surfaces, the plurality of reaction volumes comprises a plurality of through-holes, and the plurality of through-holes are disposed between the opposing surfaces.

2. The system of claim 1, wherein the illumination source is configured to simultaneously illuminate an entirety of the reaction volumes.

3. The system of claim 1, wherein the illumination source comprises a light emitting diode.

4. The system of claim 1, wherein the end-point PCR analysis comprises genotyping.

5. The system of claim 1, wherein the reaction volumes have a density greater than one reaction volume per 0.25 mm².

6. The system of claim 1, wherein the sample holder comprises at least 3072 reaction volumes, the plurality of samples being disposed within respective ones of the 3072 reaction volumes.

7. The system of claim 1, further comprising a thermal cycler configured to cycle the plurality of samples over a temperature range.

8. The system of claim 1, wherein the system further comprises a liquid, wherein the liquid comprises at least one of a mineral oil, a silicon oil, or a perfluorinated hydrocarbon.

9. The system of claim 1, wherein the analysis software is configured to perform a quantitative PCR.