Temperature control method and apparatus

1. A method of controlling temperature of a liquid held within a reaction container, said method comprising:

a) providing a thermal cycling apparatus comprising a chamber containing the reaction container, a heater, and a temperature sensor;

b) determining a sensed chamber temperature T S from the temperature sensor in the chamber;

c) calculating an effective air temperature T Eff in the chamber using the sensed chamber temperature T S and an air thermal model;

d) calculating the temperature of the liquid T L using the effective air temperature T Eff in the chamber and a liquid thermal model; and,

e) selectively heating or cooling air in the chamber using the heater, in accordance with the temperature of the liquid T L ,

f) determining if the chamber is closed; and,

g) at least one of:

i) if the chamber is closed, calculating the effective air temperature T Eff in the chamber using the sensed chamber temperature T S and a closed chamber model; and,

ii) if the chamber is open, calculating the effective air temperature T Eff in the chamber using the sensed chamber temperature T S , a sensed ambient temperature T AM and an open chamber model.

2. The method according to claim 1 , wherein said method includes:

h) determining a sensed ambient temperature T AM from a temperature sensor outside the chamber; and,

i) calculating the effective air temperature T Eff in the chamber at least in part using the sensed ambient temperature T AM , the sensed chamber temperature T S and an air thermal model.

3. The method according to claim 1 , wherein said method includes, for the closed chamber model:

h) comparing the sensed chamber temperature T S to a threshold temperature T T ; and,

i) at least one of:

i) if the sensed chamber temperature T S is below the threshold temperature T T , calculating the effective air temperature T Eff in the chamber using a first closed chamber model; and,

ii) if the sensed chamber temperature T S is above the threshold temperature T T , calculating the effective air temperature T Eff using a second closed chamber model.

4. The method according to claim 3 , wherein the effective air temperature T Eff in the chamber is determined at least in part using the relationship:

T

SS

=

{

k

SL

⁢

T

S

+

c

L

,

if

⁢

⁢

T

S

<

T

T

k

SU

⁢

T

S

+

c

U

,

if

⁢

⁢

T

S

≤

T

T

where:

T SS is a closed chamber model air temperature;

T S is the sensed chamber temperature;

T T is a threshold temperature;

k SL is a first closed chamber model coefficient;

k SU is a second closed chamber model coefficient;

c L is a first closed chamber model offset value;

c U is a second closed chamber model offset value.

5. The method according to claim 1 , wherein for the open chamber model, said method includes, calculating the effective air temperature T Eff in the chamber at least in part using the relationship:

T OC −k SS T SS +k AM T AM +c OC

where:

T OC is an open chamber model air temperature;

T SS is a closed chamber model air temperature;

T AM is a sensed ambient temperature;

k SS is a first open chamber model coefficient;

k AM is a second open chamber model coefficient;

c OC is an open chamber model offset value.

6. The method according to claim 1 , wherein said method includes calculating said effective air temperature T Eff at least in part using the relationship:

T

Eff

=

{

T

SS

,

if

⁢

⁢

the

⁢

⁢

chamber

⁢

⁢

is

⁢

⁢

closed

T

OC

,

if

⁢

⁢

the

⁢

⁢

chamber

⁢

⁢

is

⁢

⁢

open

where:

T Eff is the effective air temperature.

7. The method according to claim 1 , wherein said method includes determining said temperature of the liquid T L at least in part using the relationship:

T L ( n )=(1− k E −k L ) T L ( n− 1)+ k L T L ( n− 2)+ k E T Eff ( n )

where:

n is a discrete time interval;

T L (n) is the temperature of the liquid at time n;

T Eff (n) is the effective air temperature in the chamber at time n;

k E is a first liquid model coefficient;

k L is a second liquid model coefficient.

8. The method according to claim 1 , wherein step 3) comprises, before heating or cooling air in the chamber using the heater:

i) determining a target temperature of the liquid T LS ;

ii) determining a target air temperature T AS in the chamber in accordance with the target temperature of the liquid T LS ; and,

iii) selectively heating or cooling air in the chamber using the heater, in accordance with the target air temperature T AS in the chamber.

9. The method according to claim 8 , wherein said method includes:

h) determining a change in target temperature of the liquid ΔT LS ;

i) comparing the change ΔT LS to a threshold ΔT OSTH ,

j) at least one of:

i) if the change ΔT LS is less than the threshold ΔT OSTH , determining the target air temperature T AS in the chamber to be the target temperature of the liquid T LS ; and,

ii) if the change ΔT LS is more than the threshold ΔT OSTH , calculating the target air temperature T AS in the chamber in accordance with the target temperature of the liquid T LS and a temperature of the liquid T LM ; and

k) if the change ΔT LS is more than the threshold ΔT OSTH , calculating the air target temperature T AS using the relationship:

T AS ( n )= T LS +k OF ( T LS −T LM ( n ))

where:

T AS (n) is the air target temperature at any given discrete time n;

T LS is the target liquid temperature;

k OF is an overshoot factor constant;

T LM (n) is a liquid temperature at any given discrete time n.

10. The method according to claim 1 further comprising a calibration procedure using one reference constant obtained from a data store, wherein the calibration procedure comprises determining at least one closed chamber model constant by:

i) gradually increasing a chamber temperature with the chamber closed;

ii) detecting a change in each of at least three markers provided in the chamber, each of the at least three markers being adapted to undergo a detectable change at a respective marker temperature;

iii) determining a sensed chamber temperature Ts for each marker change; and

iv) determining the at least one closed chamber model constant using the sensed chamber temperature Ts and a corresponding marker temperature.

11. The method according to claim 1 , further comprising a calibration procedure using one reference constant obtained from a data store, wherein the calibration procedure comprises determining at least one liquid model constant for a given liquid volume by:

performing a number of thermal cycling runs;

for each run:

i) monitoring a characteristic of a liquid sample provided in the chamber when the chamber is closed, the sample characteristic being indicative of a liquid temperature T L of the liquid sample, wherein the characteristic is fluorescence;

ii) determining at least one liquid temperature T L using the characteristic;

iii) determining at least one sensed chamber temperature T S corresponding to the at least one liquid temperature T L ;

iv) determining an effective air temperature T Eff in the chamber using the at least one sensed chamber temperature and a closed thermal model; and

performing a regression analysis to relate the effective air temperature T Eff to the liquid temperature T L to thereby determine the at least one liquid model constant.

12. The method according to claim 11 , wherein the calibration procedure comprises:

determining at least one liquid model constant for a number of given liquid volumes; and

interpolating at least one liquid model constant for intermediate liquid.

13. The method according to claim 1 , further comprising a calibration procedure using one reference constant obtained from a data store, wherein the calibration procedure comprises determining at least one open chamber model constant by:

changing a chamber temperature with the chamber open;

monitoring a characteristic of a liquid sample provided in the chamber, the sample characteristic being indicative of a liquid temperature T L of the liquid sample;

determining a number of liquid temperatures T L using the characteristic;

determining a number of sensed chamber temperatures Ts and sensed ambient temperatures T AM corresponding to the number of liquid temperatures T L ;

determining a number of effective air temperatures T Eff using the number of sensed chamber temperatures Ts and a closed thermal model; and

determining a number of effective air temperatures T Eff using the number of liquid temperatures T L and a liquid thermal model; and

determining at least one open chamber model constant using the effective air temperatures T Eff and the sensed chamber temperature Ts and sensed ambient temperature T AM .

14. The method according to claim 1 , wherein said method is performed at least in part using a controller of a thermal cycling apparatus, said controller including a processor and a memory.

15. The method according to claim 14 , wherein said processor is for:

receiving a sensed chamber temperature Ts from a temperature sensor in the chamber;

determining an air temperature T Eff using the sensed chamber temperature Ts and an air thermal model stored in memory;

determining a liquid temperature T L using the air temperature T Eff and a liquid thermal model stored in memory; and

controlling at least one of a heater, a fan and a vent flap to thereby selectively heat and/or cool air in the chamber in accordance with the liquid temperature T L .

16. An apparatus for controlling temperature of a liquid held within a reaction container, said apparatus comprising:

a) a thermal cycling apparatus comprising a chamber containing the reaction container, a heater, and a temperature sensor; and

b) a controller for:

i) determining a sensed chamber temperature Ts from the temperature sensor in the chamber;

ii) calculating an effective air temperature T Eff in the chamber using the sensed chamber temperature Ts and an air thermal model;

iii) calculating the temperature of the liquid T L using the effective air temperature T Eff in the chamber and a liquid thermal model; and,

iv) selectively heating and/or cooling air in the chamber using the heater, in accordance with the temperature of the liquid T L ;

wherein the controller is comprising a processor and a memory;

wherein said memory is for storing:

a liquid thermal model;

an air thermal model; and at least one of

a closed chamber thermal model;

an open chamber thermal model; and/or,

at least one model constant.

17. The apparatus according to claim 16 , wherein said processor is for:

a) receiving the sensed chamber temperature T S from the temperature sensor in the chamber;

b) calculating the effective air temperature T Eff in the chamber using the sensed chamber temperature T S and an air thermal model stored in the memory;

c) calculating the temperature of the liquid T L using the air temperature T Eff and the liquid thermal model stored in the memory; and,

d) controlling at least one of a heater, a fan and a vent flap to thereby selectively heat and/or cool air in the chamber in accordance with the temperature of the liquid T L .

18. The apparatus according to claim 17 , wherein said controller is coupled to at least one of:

a) a chamber temperature sensor for sensing a chamber temperature T S ;

b) an ambient temperature sensor for sensing an ambient temperature T AM ;

c) a heater for heating the chamber;

d) a fan for cycling ambient air through the chamber; and,

e) a vent flap for closing the chamber.

19. A method of determining temperature of a liquid T L held within a reaction container in a chamber of a thermal cycling apparatus, said method including:

a) providing a thermal cycling apparatus comprising a chamber containing the reaction container, a heater, and a temperature sensor;

b) determining a sensed chamber temperature T S from the temperature sensor in the chamber;

c) calculating an effective air temperature T Eff in the chamber using the sensed chamber temperature T S and an air thermal model;

d) calculating the temperature of the liquid T L using the effective air temperature T Eff in the chamber and a liquid thermal model, and

e) at least one of:

i) if the chamber is closed, the effective air temperature T Eff is calculated in step b) using the sensed chamber temperature T S and a closed chamber model; and,

ii) if the chamber is open, the air temperature T Eff is calculated in step b) using the sensed chamber temperature T S , a sensed ambient temperature T AM and an open chamber model.

20. An apparatus for determining the temperature of a liquid T L held within a reaction container, said apparatus comprising:

a) a thermal cycling apparatus comprising a chamber containing the reaction container, a heater, and a temperature sensor; and

b) a processor for:

i) determining a sensed chamber temperature T S from the temperature sensor in the chamber;

ii) calculating an effective air temperature T Eff in the chamber using the sensed chamber temperature T S and an air thermal model; and,

iii) calculating the temperature of the liquid T L using the effective air temperature T Eff in the chamber and a liquid thermal model;

c) a memory for storing:

i) a liquid thermal model;

ii) an air thermal model; and at least one of

iii) a closed chamber thermal model;

iv) an open chamber thermal model; and/or,

v) at least one model constant.