SYSTEMS AND DEVICES FOR ISOTHERMAL BIOCHEMICAL REACTIONS AND/OR ANALYSIS

• US 20080229849A1
• Filed: 03/21/2008
• Published: 09/25/2008
• 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
• Inventors: Hickerson, Anna, Nadim, Ali, Doebler, Robert W., Sterling, James D., Cooney, Christopher
• Granted Patent: US 8,153,064 B2
• Time in Patent Office: Days
• US Class Current: 73/864.91
• 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;

an excitation subsystem including at least a first plurality of excitation sources positioned at least partially in the receiver 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 temperature of the receiver at least approximately constant for a period of time sufficient to perform an isothermal reaction on the samples.

2. 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.

3. The system of claim 2 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.

4. The system of claim 1, further comprising:

at least one filter positioned between at least one excitation source and the 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.

5. The system of claim 1, further comprising:

at least one filter positioned between at least one of the detectors and the 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.

6. 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.

7. The system of claim 6 wherein the at least one heater element is conductively thermally coupled to the receiver to provide heat to the sample holders via the receiver.

8. The system of claim 7 wherein the receiver has a large thermal mass with respect to the samples.

9. The system of claim 1 wherein the receiver is 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 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, and the excitation sources are 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.

10. The system of claim 9 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.

11. The system of claim 10 wherein the receiver is formed from aluminum.

12. The system of claim 1 wherein the receiver is 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 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, and the excitation sources are 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.

13. The system of claim 1 wherein the excitation subsystem includes a number of light emitting diodes at least some of which are operable to emit electromagnetic energy in at least two distinct bands.

14. The system of claim 1 wherein the detectors of the detection subsystem include a number of photodiodes that are responsive to electromagnetic energy in at least of a portion of the electromagnetic spectrum between an ultraviolet portion of the electromagnetic spectrum and an infrared portion of the electromagnetic spectrum, inclusive.

15. The system of claim 1 wherein the excitation subsystem includes a number of light emitting diodes at least some of which are operable to emit electromagnetic energy in at least of a portion of the electromagnetic spectrum between an ultraviolet portion of the electromagnetic spectrum and an infrared portion of the electromagnetic spectrum, inclusive.

16. The system of claim 14 wherein the detectors of the detection subsystem include a number of photodiodes that are responsive to electromagnetic energy in a portion of the electromagnetic spectrum that is different from the portion of the electromagnetic spectrum in which the light emitting diodes emit.

17. The system of claim 1, further comprising:

the plurality of sample holders, wherein each of the sample holders comprises a material that filters out a portion of electromagnetic energy emitted by the excitation subsystem and passes a portion of electromagnetic energy emitted by the excitation subsystem.

18. The system of claim 1, further comprising:

the plurality of sample holders, wherein each of the sample holders comprises a material that filters a portion of electromagnetic energy emitted by a number of samples held in respective ones of the sample holders in response excitation by electromagnetic energy from the excitation subsystem.

19. The system of claim 1 wherein the receptacles are spaced from one another by a distance selected from 2.25 mm, 4.5 mm and 9 mm.

20. The system of claim 1, further comprising:

at least one controller configured to provide control signals to at least one of modulate or pulsate the excitation sources and to select a component of a response signal from the detection elements based on the modulation or pulsation of the excitation sources.

21. The system of claim 1 wherein the at least one controller is configured to perform Fourier transformation on the response signal to improve a signal-to-noise ratio of the system.

22. The system of claim 1, further comprising:

at least one controller configured to provide respective control signals to at least one of modulate or pulsate the excitation sources at respective frequencies and to select a component of a response signal from the detection elements based on the modulation or pulsation of the excitation sources.

23. The system of claim 1 wherein there are at least two excitation sources and one detector per receptacle, where each of at least two of the excitation sources per receptacle emit at different wavelengths, and further comprising:

at least one controller configured to operate a first one of the two excitations sources of a first receptacle at a first frequency and a second one of the excitation sources of the first receptacle at a second frequency, different from the first frequency, and to demodulate a response signal from the detector based on the first and the second frequencies.

24. The system of claim 23 wherein the at least one controller is configured to determine at least one piece of information about a first biochemical reaction occurring in the first receptacle and at least one piece of information about a second biochemical reaction occurring in the first receptacle based on the demodulated response signal.

25. The system of claim 1, further comprising:

at least one controller configured to vary a current supplied to the excitation sources to cause each of the excitation sources to emit a first wavelength at a first time and a second wavelength different from the first wavelength at a second time.

26. A sample holder for use with a system that excites a sample received in the sample holder with optical electromagnetic energy and detects optical electromagnetic energy returned by the sample, comprising:

a side wall member at least a portion of which provides an optical path between an exterior of the sample holder and an interior of the sample holder that filters a first band of wavelengths of optical electromagnetic energy in a range of optical electromagnetic energy emitted by an excitation source of a system and passes a second band of wavelengths of optical electromagnetic energy detectable by a detector of the system, where optical electromagnetic energy consists of electromagnetic energy between an ultraviolet and an infrared portion of the electromagnetic spectrum, inclusive.

27. The sample holder of claim 26 wherein the sample holder is sealed during use.

28. The sample holder of claim 26 wherein at least a bottom portion of the side wall member provides the optical path between an exterior of the sample holder and an interior of the sample holder.

29. The sample holder of claim 26 wherein the sample holder has an upper portion that is selectively sealable.

30. The sample holder of claim 26 wherein the second band of wavelengths of optical electromagnetic energy is different from the first band of wavelengths of optical electromagnetic energy.

31. The sample holder of claim 26 the side wall member is an elongated tubular member.

32. The sample holder of claim 26 the side wall member is an elongated tubular member with a tapered bottom portion and an upper portion with an opening from at a top.

33. The sample holder of claim 32, further comprising:

a cap selectively positionable with respect to the side wall member to seal the opening.

34. The sample holder of claim 26 the side wall member is substantially planar with a number of wells formed therein.

35. The sample holder of claim 26 the side wall member comprises a filtering material.

36. The sample holder of claim 26 the side wall member includes at least one of a coating or a layer of a filtering material.