METHODS TO AUTOMATICALLY CALIBRATE PH SENSORS WITHOUT SAMPLING
Methods of calibrating a pH sensor fixed within an enclosed vessel are disclosed. The methods include introducing a buffer into the enclosed vessel, introducing a gas mixture comprising CO 2 into the enclosed vessel, measuring a pH signal of the solution, measuring a CO 2 concentration of a headspace gas of the solution, and calculating a pH value with a buffer calibration curve. The methods include calculating a calibration parameter with a sensor calibration curve and calibrating the pH sensor with the calibration parameter. Reactor systems are also disclosed. The systems include an enclosed reactor, a pH sensor, a CO 2 sensor, a temperature control subsystem, and a controller. Methods of facilitating pH sensor calibration without sampling in a bioreactor system are also disclosed. The methods include providing a controller and providing instructions to operably connect the controller to the pH sensor and the CO 2 sensor.
1 . A reactor system, comprising:
an enclosed reactor fluidly connectable to a source of a buffer and having a pH sensor positioned to measure pH of a fluid within the reactor and a CO 2 sensor positioned to measure CO 2 concentration within the reactor,
a source of a gas mixture comprising CO 2 fluidly connected to the enclosed reactor;
a temperature control subsystem configured to control temperature of the fluid within the reactor; and
a controller operably connected to the pH sensor and the CO 2 sensor, the controller being configured to:
calculate a pH value from a CO 2 concentration measurement obtained by the CO 2 sensor with a calibration curve for the buffer;
calculate a calibration parameter for the pH sensor from a pH signal obtained by the pH sensor and the pH value with a calibration curve for the pH sensor; and
calibrate the pH sensor with the calibration parameter.
2 . The reactor system of claim 1 , wherein the enclosed reactor is a microbioreactor.
3 . The reactor system of claim 1 , wherein the enclosed reactor is sterile.
4 . The reactor system of claim 1 , wherein the enclosed reactor is fluidly connectable to a source of a humidification solution.
5 . The reactor system of claim 1 , wherein the CO 2 sensor is positioned to measure CO 2 concentration of a headspace gas within the enclosed reactor.
6 . The reactor system of claim 1 , wherein the controller is operably connected to at least one of the source of the buffer and the source of the gas mixture, and further configured to introduce at least one of the buffer and the gas mixture into the enclosed reactor.
7 . The reactor system of claim 1 , wherein the controller is configured to calculate parameters A, B, and C in the calibration curve for the buffer having a formula in the form of:
pH
fit
=
A
+
B
*
log
10
(
C
+
CO
2
perc
)
where A, B, and C are fitting parameters and CO 2perc is the measured CO 2 concentration as a percentage of the headspace gas total composition.
8 . The reactor system of claim 1 , wherein the controller is configured to calculate parameters W, X, Y, and Z in the calibration curve for the pH sensor having a formula in the form of:
pH
sensor
=
(
log
2
(
S
-
W
)
-
log
2
(
X
-
S
)
)
*
Y
+
Z
,
where W, X, Y, and Z are fitting parameters and S is the pH sensor signal.
9 . A method of facilitating pH sensor calibration without sampling in a bioreactor system comprising an enclosed bioreactor, a pH sensor positioned to measure pH of a fluid within the bioreactor, and a CO 2 sensor positioned to measure CO 2 concentration within the bioreactor, the method comprising:
providing a controller configured to:
calculate a pH value from a CO 2 concentration obtained by the CO 2 sensor with a calibration curve for the buffer,
calculate a calibration parameter for the pH sensor from a pH signal obtained by the pH sensor and the pH value with a calibration curve for the pH sensor, and
calibrate the pH sensor with the calibration parameter,
instructing a user to operably connect the controller to the pH sensor; and
instructing the user to operably connect the controller to the CO 2 sensor.
10 . The method of claim 9 , further comprising providing at least one of the pH sensor and the CO 2 sensor.