Systems and devices for isothermal biochemical reactions and/or analysis

• US 8,153,064 B2
• Filed: 03/21/2008
• Issued: 04/10/2012
• Est. Priority Date: 03/22/2007
• Status: Active Grant

• Current Assignee: Claremont Biosolutions, LLC
• Original Assignee: Ali Nadim, Anna Hickerson, Christopher Cooney, James D. Sterling, Robert W. Doebler II
• Inventors: Cooney, Christopher, Hickerson, Anna, Sterling, James D., Nadim, Ali, Doebler, Robert W. II
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): HAMMOND, CHARLES
• Application Number:
  US12/052,950
• Publication Number:
  US 20080229849A1
• Time in Patent Office: 1,481 Days
• Field of Search: None
• US Class Current: 422/82.08
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/0609 Holders integrated in container to position an object
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1827 using resistive heater
• 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 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08
• 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 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2201/06153 the sources being LED's
• CPC Class Codes: Y10T 436/12 Condition responsive control
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

An isothermal reaction and analysis system may include a receiver to receive sample holders, a thermal control subsystem to control a temperature of the receiver, an excitation subsystem, a detection subsystem and an analysis subsystem. Excitation sources and/or detectors are positioned to enhance data collection. Sample holders may include filters, selectively blocking and passing wavelengths or bands of electromagnetic radiation.

Claims

1. A system to support biochemical reactions, comprising:

a receiver having a plurality of receptacles formed therein, each of the receptacles sized to at least partially receive and support a respective one of a plurality of sample holders, the receiver including an elongated metal bar, having the plurality of receptacles formed in an upper face of the metal bar, each of the receptacles having a diameter that is sized to closely receive a diameter of a respective one of the plurality of sample holders, the receiver further having a pair of angled faces each forming an obtuse angle between the respective one of the angle faces and the upper face and each of the angled faces having a respective set of passages, each of the passages extending from an exterior of the metal bar to an interior in communication with a respective one of the receptacles;

an excitation subsystem including at least a first plurality of excitation sources positioned at least partially in the receiver, the excitation sources positioned at least partially in respective ones of the passages with a portion of each of the excitation sources proximate respective ones of the receptacles to direct electromagnetic energy toward at least a portion of a respective one of the sample holders received in a respective one of the receptacles of the receiver, the excitation subsystem operable to excite with the electromagnetic energy each of a number of samples contained in respective ones of a plurality of the sample holders while the sample holders are received and supported by the receiver;

a detection subsystem that includes a plurality of detectors, each of the detectors positioned to detect emission of electromagnetic energy from a respective sample contained in a respective one of the sample holders that are received and supported by the receiver; and

a thermal control subsystem operable to at least approximately maintain a uniform temperature of the receiver at least approximately constant for a period of time sufficient to perform an isothermal reaction on the samples, wherein the receiver has a large thermal mass with respect to the samples.

2. The system of claim 1 wherein the receiver has a number of openings formed in a lower face, the lower face opposed to the upper face, and the detectors of the detection subsystem are positioned at least partially in respective ones of the openings with a portion of each of the detectors proximate respective ones of the receptacles.

3. The system of claim 2 wherein the receiver is formed from aluminum.

4. The system of claim 1 wherein the excitation subsystem includes a second plurality of excitation sources, each of the excitation sources of the second plurality of excitation sources positioned at least partially in the receiver to direct the electromagnetic energy toward at least a portion of a respective one of the sample holders received in a respective one of the receptacles of the receiver, the electromagnetic energy directed by the excitation sources of the second plurality of excitation sources being of a different wavelength than the electromagnetic energy directed by the excitation sources of the first plurality of excitation sources.

5. The system of claim 4 wherein each of the excitation sources is positioned completely within a respective passage in the receiver to direct the electromagnetic energy toward only a base portion of the respective sample holder when the sample holder is positioned in the respective one of the receptacles, the base portion at least proximate a bottom of the sample holder when supported by the receiver.

6. The system of claim 1, further comprising:

at least one filter positioned between at least one excitation source and at least one of the sample holders when the at least one of the sample holders is received by the respective receptacle of the receiver.

7. The system of claim 1, further comprising:

at least one filter positioned between at least one of the detectors and at least one of the sample holders when the at least one of the sample holders is received by the respective receptacle of the receiver, the at least one filter operative to filter at least a portion of the electromagnetic energy emitted by at least one of the excitation sources.

8. The system of claim 1 wherein the thermal control subsystem includes at least one temperature sensor operable to detect a temperature at least proximate the sample holders that is indicative of a temperature of a biochemical reaction within the sample holders and at least one heater element operable to provide heat to the receiver in response to a difference between the detected temperature and at least one set temperature.

9. The system of claim 8 wherein the at least one heater element is conductively thermally coupled to the receiver to provide heat to the sample holders via the receiver.

10. The system of claim 9 wherein the thermal mass of the receiver is at least ten times as large as the thermal mass of the samples.

11. The system of claim 1 wherein the receiver is formed from aluminum.

12. A system to support biochemical reactions, comprising:

a receiver having a plurality of receptacles formed therein, each of the receptacles sized to at least partially receive and support a respective one of a plurality of sample holders, the receiver including an elongated metal bar having the plurality of receptacles formed in an upper face of the metal bar, each of the receptacles having a diameter that is sized to closely receive and support a diameter of a respective one of the plurality the sample holders, the receiver further having a number of passages formed in a lower face diametrically opposed to the upper face, each of the passages extending from an exterior of the metal bar to an interior in communication with a respective one of the receptacles;

an excitation subsystem including at least a first plurality of excitation sources positioned at least partially in the receiver, the excitation sources positioned at least partially in respective ones of the passages with a portion of each of the excitation sources proximate respective ones of the receptacles to direct electromagnetic energy toward at least a portion of a respective one of the sample holders received in a respective one of the receptacles of the receiver, the excitation subsystem operable to excite with the electromagnetic energy each of a number of samples contained in respective ones of a plurality of the sample holders while the sample holders are received and supported by the receiver;

a detection subsystem that includes a plurality of detectors, each of the detectors positioned to detect emission of electromagnetic energy from a respective sample contained in a respective one of the sample holders that are received and supported by the receiver; and

a thermal control subsystem operable to at least approximately maintain a uniform temperature of the receiver at least approximately constant for a period of time sufficient to perform an isothermal reaction on the samples, wherein the receiver has a large thermal mass with respect to the samples.

13. The system of claim 12 wherein each of the excitation sources is positioned completely within a respective one of the plurality of passages in the receiver to direct the electromagnetic energy toward only a base portion of the respective sample holder when the sample holder is positioned in the respective one of the receptacles, the base portion at least proximate a bottom of the sample holder when supported by the receiver.

14. The system of claim 12 further comprising:

at least one filter positioned between at least one excitation source and at least one of the sample holders when the at least one of the sample holders is received by the respective receptacle of the receiver.

15. The system of claim 12, further comprising:

at least one filter positioned between at least one of the detectors and at least one of the sample holders when the at least one of the sample holders is received by the respective receptacle of the receiver, the at least one filter operative to filter at least a portion of the electromagnetic energy emitted by at least one of the excitation sources.

16. The system of claim 12 wherein the thermal control subsystem includes at least one temperature sensor operable to detect a temperature at least proximate the sample holders that is indicative of a temperature of a biochemical reaction within the sample holders and at least one heater element operable to provide heat to the receiver in response to a difference between the detected temperature and at least one set temperature.

17. The system of claim 16 wherein the at least one heater element is conductively thermally coupled to the receiver to provide heat to the sample holders via the receiver.

18. The system of claim 17 wherein the thermal mass of the receiver is at least ten times as large as the thermal mass of the samples.