Methods and apparatus for direct heating of biological material

• US 5,721,123 A
• Filed: 01/05/1996
• Issued: 02/24/1998
• Est. Priority Date: 01/05/1996
• Status: Expired due to Fees

• Current Assignee: Microfab Technologies, Inc.
• Original Assignee: Microfab Technologies, Inc.
• Inventors: Frederickson, Christopher J., Wallace, David B., Hayes, Donald J.
• Primary Examiner(s): Jordan, Charles T.
• Assistant Examiner(s): Hardee, John R.
• Application Number:
  US08/583,425
• Time in Patent Office: 781 Days
• Field of Search: 250/504 R, 250/454.11, 250/455.11, 250/493.1, 422/52, 422/62, 422/68.1, 422/82.08, 422/82.09, 422/82.12, 422/109, 435/290, 435/291, 435/91.1, 435/6, 435/7.1, 435/91.2, 935/78, 935/79, 935/87, 935/88, 436/501
• US Class Current: 435/91.1
• 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 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2523/313 Irradiation, e.g. UV irradiation
• CPC Class Codes: G01N 1/44 Sample treatment involving radiation, e.g. heat

Abstract

Biological material is cycled through a sequence of temperatures by containing the material in a vessel positioned in a chamber maintained at a temperature which is no higher than the lowest temperature in a predetermined temperature sequence. The vessel is then irradiated with varying levels of electromagnetic radiation to heat the material and cycle it through a sequence of predetermined temperatures.

Claims

1. A method of cycling biological material through a sequence of temperatures for effecting a bio-chemical reaction, including at least an initial reaction temperature and an elevated reaction temperature above the initial reaction temperature, comprising the steps of:

(a) placing biological material in a vessel;

(b) selecting a thermochromic material which has a phase change at the elevated reaction temperature;

(c) placing the selected thermochromic material in the vessel;

(d) irradiating the contents of the vessel with an amount of electromagnetic radiation sufficient to raise the biological material in the vessel to the elevated reaction temperature; and

(e) controlling the temperature of the vessel at the elevated reaction temperature for a reaction time by means of the phase change in the thermochromic material.

2. The method of claim 1 further including the step of sensing the phase change of the thermochromic material at or just above the elevated reaction temperature to indicate the temperature of the biological material.

3. The method of claim 1 wherein the step of selecting the thermochromic material comprises the step of selecting a thermochromic material which has a state between the initial reaction temperature and the elevated reaction temperature which absorbs said electromagnetic radiation and the step of irradiating the contents of the vessel includes the step of raising the temperature of said contents to the elevated reaction temperature by means of absorption of the electromagnetic radiation in the thermochromic material.

4. The method of claim 3 wherein the step of selecting the thermochromic material comprises the step of selecting a thermochromic material which has a state above the phase change at the elevated reaction temperature which does not absorb said electromagnetic radiation whereby the step of controlling the elevated reaction temperature is obtained by clamping caused by repeated phase changes in the thermochromic material.

5. The method of claim 4 further including the step of sensing the phase change of the thermochromic material at or just above the elevated reaction temperature to indicate the temperature of the biological material.

6. A method as set forth in claim 4 including the step of analyzing the results of any reaction involving the biological material as a result of temperature cycling.

7. A method as set forth in claim 6 wherein the step of analyzing the results of the reaction includes labeling the biological material with a fluorescent material, exposing the vessel to a second light source, and measuring the response of the fluorescent material to the second light source.

8. A method as set forth in claim 6 wherein results of the reaction are analyzed using absorptometric analysis.

9. The method of claim 4 wherein the step of irradiating the contents of the vessel is the step of irradiating with laser energy and the steps of selecting and placing a thermochromic material in the vessel are carided out with a thermochromic material which absorbs said laser energy before said phase change at the elevated reaction temperature and does not absorb said laser energy after said phase change at the elevated reaction temperature.

11. The method of claim 9 further including the step of determining when the contents of the vessel have reached the elevated reaction temperature by sensing the change of state in the thermochromic material.

10. A method of cycling biological material through a sequence of temperatures for effecting a bio-chemical reaction, including at least an initial reaction temperature and an elevated reaction temperature above the initial reaction temperature, comprising the steps of:

(a) placing biological material in a vessel transparent to electromagnetic radiation;

(b) selecting a thermochromic material which has a state between the initial reaction temperature and the elevated reaction temperature which absorbs electromagnetic radiation and different state at or just above the elevated reaction temperature which does not absorb said electromagnetic radiation;

(c) placing the selected thermochromic material in the vessel;

(d) irradiating the contents of the vessel with an amount of said electromagnetic radiation more than sufficient to raise the contents in the vessel to the elevated reaction temperature; and

(e) clamping the temperature of the contents of the vessel for a reaction time during continued electromagnetic radiation by means of changes of state of the thermochromic material for a reaction time to keep the temperature of the vessel contents close to the elevated reaction temperature.

12. The method of claim 10 wherein the step of irradiating the contents of the vessel is the step of irradiating with laser energy and the steps of selecting and placing a thermochromic material in the vessel are carried out with a thermochromic material which absorbs said laser energy before said phase change at the elevated reaction temperature and does not absorb said laser energy after said phase change at the elevated reaction temperature.