Instruments for processing cells
Disclosed herein is an instrument suitable for processing cells for example culturing, concentrating or washing said cells, the instrument comprising: a housing for accommodating mechanical elements including at least one fluid pump; and a disposable processing kit complementary to the mechanical elements within the housing and comprising a fluid circuit including a fluid reservoir and plural fluid paths capable of carrying fluid flow caused by said pump(s), the instrument further including a mechanism for determining the quantity, or change in quantity of the fluid in the reservoir resulting from said fluid flow, the instrument yet further comprising a controller operable to control at least the pump and operable to perform a fault determination process, which includes the steps of determining the expected flow rate of said pump(s) calculated from the speed of the pump(s) and comparing that expected flow with the change in quantity of the fluid in the reservoir as determined by said mechanism.
1. An instrument for processing cells including culturing, concentrating or washing said cells that is adaptable to receive a disposable processing kit comprising a fluid circuit including a fluid reservoir and plural fluid paths capable of carrying fluid flow, the instrument comprising:
a housing accommodating mechanical elements including at least one fluid pump that is adaptable to receive the disposable processing kit and provide fluid flow, by the at least one fluid pump, to the plural fluid paths;
a mechanism configured for determining a quantity or a change in quantity of the fluid in the reservoir resulting from said fluid flow, and
a controller programmed to control said at least one fluid pump and operable to perform a fault determination process, which includes steps of:
determining an expected flow rate of said at least one fluid pump calculated from the speed of said at least one fluid pump;
comparing the expected flow rate with the change in quantity of the fluid in the reservoir as determined by said mechanism; and
producing an error or fault condition based at least in part on a determination that said comparison produces a difference between the expected flow rate of said at least one fluid pump over a predetermined time period, and the change in quantity of the fluid in the reservoir over the predetermined time period, wherein the difference is above a predetermined value.
2. The instrument of claim 1 , wherein the predetermined value is dependent on an average pump speed over the time period.
3. The instrument of claim 1 , wherein the predetermined value increases with pump speed.
4. The instrument of claim 1 , wherein said quantity is fluid mass and said mechanism is a weighing mechanism.
5. The instrument of claim 4 , wherein said weighing mechanism includes a load cell and a support mechanically connected to the load cell for supporting the fluid reservoir and for transferring the weight of the fluid reservoir to the load cell.
6. The instrument of claim 1 , wherein said quantity is fluid volume and said mechanism determines fluid volume.
7. The instrument of claim 1 , wherein said at least one fluid pump includes a peristaltic mechanism acting on a sealed fluid tube of the processing kit circuit, and the expected mass flow from said at least one fluid pump is calculated from the speed of the peristaltic mechanism.
8. The instrument of claim 1 , wherein said disposable processing kit is insertable into and removable from the housing as an assembly, and the fluid circuit is separate from the mechanical elements of the remaining instrument.
9. The instrument of claim 1 , wherein the instrument is operable to derived the error or fault condition from equations 1 and 2, where appropriate substituting volume for mass in said equations
Absolute Value (Expected Flow Rate−Actual Flow Rate)>Error Criterion, wherein the Actual Mass Flow Rate is determined by the change in the signal from the load cell over the fixed measurement period, N seconds and Equation 1
used to compute the flow rate error check: Equation 2
Abs
[
∑
0
N
1
/
fs
(
Actual
Pump
Speed
DependentPump
)
N
1
/
fs
×
γ
Dependent
Pump
+
∑
0
N
1
/
fs
(
Actual
PumpSpeed
PrimaryIndependent
Pump
)
N
1
/
fs
×
γ
PrimaryIndependent
Pump
-
(
Mass
N
-
Mass
0
)
N
*
min
/
6
sec
]
>
Error
Criterion
Where:
N is the measurement period in seconds (a configuration parameter):
f S is the measurement sample frequency in Hz.
Thus
N
1
/
fs
is the number of samples in the measurement period:
Actual pump speed is in RPM:
Dependent Pump and Independent Pump subscripts designate different pumps controlled by the controller:
γ (Gamma) is the pump constant in ml/min/RPM:
Mass N is the mass at sample N during the integration period: and
Mass 0 is the starting mass.
10. A method for determining fluid mass or volumetric flow faults in a cell processing instrument that includes: a housing for accommodating mechanical elements including at least one fluid pump; a processing kit complementary to the mechanical elements within the housing having a fluid circuit including a fluid reservoir, and plural fluid paths capable of carrying fluid flow caused by said at least one fluid pump, a mechanism configured for determining a quantity, or a change in quantity of fluid in the fluid reservoir resulting from said fluid flow, and a controller operable to control at least the pump and operable to perform a flow fault determination process; the method including:
determining an expected flow rate of said at least one fluid pump calculated from the speed of said at least one fluid pump;
comparing the expected flow rate with the change in quantity of the fluid reservoir as determined by said mechanism; and
producing an error or fault condition based at least in part on a determination that said comparison produces a difference between the expected flow rate of said at least one fluid pump over a predetermined time period, and the change in quantity of the fluid in the reservoir over the predetermined time period, wherein the difference is above a predetermined value.
11. The method of claim 10 , wherein the error or fault condition is derived from equations 1 and 2, where appropriate substituting volume for mass in said equations
Absolute Value (Expected Flow Rate−Actual Flow Rate)>Error Criterion, wherein the Actual Mass Flow Rate is determined by the change in the signal from the load cell over the fixed measurement period. N seconds and Equation 1
used to compute the flow rate error check: Equation 2
Abs
[
∑
0
N
1
/
fs
(
Actual
Pump
Speed
DependentPump
)
N
1
/
fs
×
γ
Dependent
Pump
+
∑
0
N
1
/
fs
(
Actual
PumpSpeed
PrimaryIndependent
Pump
)
N
1
/
fs
×
γ
PrimaryIndependent
Pump
-
(
Mass
N
-
Mass
0
)
N
*
min
/
6
sec
]
>
Error
Criterion
Where:
N is the measurement period in seconds (a configuration parameter):
F S is the measurement sample frequency in Hz.
Thus
N
1
/
fs
is the number of samples in the measurement period:
Actual pump speed is in RPM:
Dependent Pump and Independent Pump subscripts designate different pumps controlled by the controller:
γ (Gamma) is the pump constant in ml/min/RPM:
Mass N is the mass at sample N during the integration period: and
Mass 0 is the starting mass.
12. The method of claim 10 , wherein the cells are human cells.