QbD1200 Lab TOC Analyzer
Frequently Asked Questions
1.
How does the QbD1200 avoid interferences from TIC?
A water sample initially contains two types of carbon:
•
Total Inorganic Carbon (TIC) (from dissolved CO2 gas and dissolved carbonates in the water)
•
Total Organic Carbon (TOC) (from organic species)
Added together, TIC and TOC form the Total Carbon in the water, TC.
TC = TIC + TOC
Some laboratory TOC analyzers measure TIC and TC and then calculate TOC.
TOC = TC - TIC
This method suffers from interferences when used to measure TOC in pharmaceutical grade waters, which
typically have much larger amounts of TC and TIC than TOC. The measurement inaccuracies in the
sensors used to measure TIC and TC can be much larger than the TOC, so, when the TOC is calculated, the
measurement errors can lead to an over-reporting of TOC or the reporting of a negative TOC value, e.g. in
a water sample containing 1900ppb TIC and 2000ppb TC with a sensor accuracy of +/-2%:
Measured TC = 1960ppb to 2040ppb
Measured TIC = 1862ppb to 1938ppb
Calculated TOC = TC – TIC = 22ppb to 178ppb
TOC analyzers measuring TC and TIC and calculating TOC need to report TIC for two reasons:
a)
To allow the user to check the accuracy of the TOC calculation
b) To allow the user to check that the levels of TIC do not exceed the manufacturer’s recommended
maximum (if this occurs the reported TOC values will be inaccurate and the user must find a way
to remove some or all of the TIC)
To avoid these issues, the QbD1200 directly measures the TOC. First the QbD1200 removes all TIC from
the sample, leaving just TOC in the sample. Then the TOC is oxidized to convert all organic species into
CO2 gas using a combination of UV light and persulphate. The CO2 gas is pushed out of solution using a
CO2 –free purge gas and then measured and a TOC value reported.
CO2 NDIR Detector Signal vs. Time
CO2 Signal
TIC
TOC
Turn UV
Lamp on
here
Time
Calculate
TOC from
area under
this peak
For this reason, the QbD1200 does not calculate TOC from measurements of TIC and TC.
2.
How does the QbD1200 avoid sample-to-sample carry-over?
Most TOC analyzers suffer from sample-to-sample carry-over due to varying amounts of the previous
sample remaining in the sample tube from the autosampler tray to the analyzer. For this reason the first
measurement the analyzer will report is a mixture of the new sample and a varying amount of the
previous sample. As a work-around, the user must configure the TOC analyzer to ignore the first
measurement. As a typical TOC analyzer takes around 3 minutes to carry out a TOC analysis on
pharmaceutical-grade water, this wasted sample can add over 3 hours to the time taken to analyze a tray
of 64 samples (3 minutes x 64 samples = 192 minutes).
To avoid sample-to-sample carry-over issues, the QbD1200 employs the following process:
a)
The sample line from the autosampler is back-flushed with the One reagent which is then sent to
drain
b) A sample of the next vial is draw down the sample line and then sent to drain
c)
3.
The QbD1200 now takes a sample from the vial to be analyzed, confident that the sample will
not contain any of the previous vial’s content
How does the QbD1200 Auto-Range function work?
In dissolved phase, ppb is an expression of mass, e.g. 1ppb in 1 liter of water has a mass of 0.000000001kg
(assuming the 1 liter of water has a mass of 1kg). If a 1 liter solution containing 100ppb of TOC is diluted
with a TOC-free 1 liter solution, then the resultant TOC level will be halved, i.e. 50ppb.
The QbD1200 has a measurement range of 0 to 5,000ppb. This range is extended by accurate dilution of
the sample to be tested by a factor of up to 20x, utilizing a high-accuracy syringe pump (+/-1% accuracy).
Thus the QbD1200 can analyze samples of up to 100,000ppb.
In applications where the TOC level in the samples is expected to be >4,000ppb, the auto-ranging function
can be enabled by the user using the configuration settings. First the QbD1200 draws 1mL of One Reagent
into the syringe, followed by 1mL of the sample and then 8mL more of One Reagent. The combined
solution is then dispensed into UV reaction module, a quick estimation of the TOC level is made to
determine whether there is a need for sample dilution. The level of dilution depends on the amount of
TOC present in the sample. The auto-range function can be turned off through the QbD1200 menu.
4.
How much One Reagent is needed for a tray of 64 vials?
The amount of One Reagent used depends on several factors as described below. The QbD1200 monitors
the One Reagent and will stop analyzing and display a warning on the screen if the One Reagent runs out.
The One Reagent is supplied in concentrated form in a 500mL bottle which has a 6 month shelf-life. For use
in the QbD1200, the One Reagent is diluted, using just 10mL of One Reagent mixed with 990mL of low TOC
water (<100ppb). The diluted One Reagent has a shelf-life of 7days.
Whilst the diluted One Reagent used in the QbD1200 has a 7 day shelf-life, it is expected that most
QbD1200 users will make up a fresh bottle of diluted One Reagent with every tray of 64 samples to be
analyzed.
The amount of reagent used can vary according to:
a)
The number of vials to be analyzed and number of analysis replications
For water samples with <4,000ppb TOC, just 2mL of One Reagent is consumed when analyzing each
sample from the vials loaded into the autosampler. In addition, the sample line back-flush performed
at the start of each new vial analyzed uses 5mL of One Reagent. So, for example, if the QbD1200 autoranging function was turned off and the autosampler was configured to analyze three samples from
each vial, then analyzing each vial would consume:
(3 x 2mL) + 5mL = 11mL of One Reagent/vial
b) If the auto-ranging function is enabled (if analyzing samples >4,000ppb TOC)
If the level of TOC in the vial is <4,000ppb, then each sample replicate uses just 2mL of One Reagent
(plus the initial 5mL for line back-flush – see a) above). If the level of TOC is >4,000ppb, then the One
Reagent will be used to dilute the sample, using a maximum of 9.6mL of One Reagent per sample
analysis for water with >32,000ppb, plus an initial 9mL of reagent for auto-ranging for each vial.
5.
How much sample water is required in each vial to be analyzed?
The amount of water sample required depends on the number of analysis replicates selected by the user.
For water samples with <4,000ppb TOC, 8mL of water sample is consumed when analyzing each sample
from the vials loaded into the autosampler. In addition, the sample line forward-flush performed at the
start of each new vial analyzed uses 5mL of the water sample in the vial. So, for example, if the
autosampler was configured to analyze three samples from each vial, then analyzing each vial would
consume:
(3 x 8mL) + 5mL = 29mL of water/vial
6.
How does the QbD1200 control the amount of sample drawn in for each analysis and also the dilution?
Variations in the volume of the water sample analyzed and sample dilution are one of the biggest causes of
sample-to-sample variance in many laboratory TOC analyzers.
The QbD1200 uses a high-accuracy syringe pump for measuring the volume of water sample analyzed and
the sample dilution using the One Reagent. The syringe pump achieves a volume accuracy of +/-1% by
accurate control using a stepper motor and optical encoder wheel.
A flow sensor is used to monitor the presence of the One Reagent, but the flow rate is controlled by the
stepper motor and syringe. The flow sensor and syringe are both tested each time the analyzer is powered
on and can be tested at any time by initiating the System Health Check through the QbD1200 menu.
If the user wants to check the accuracy of the stepper motor and syringe, then this can be achieved by
turning the auto-range function off, setting the QbD1200 to take three sample analyses and placing the
QbD1200 sample tube into a graduated cylinder with >50mL of low TOC water (<100ppb). The QbD1200
should extract:
(1 x 5mL forward flush) + (3 x 8mL analysis replicates) = 29mL of water
7.
How many calibration records and TOC analysis records can the QbD1200 memory hold?
The QbD1200 is designed to provide paperless electronic records via USB or over secure FTP using
Ethernet. It can also provide printed paper records via USB-connected printer. The internal memory in the
QbD1200 is 21 CFR part 11 secure and can retain approximately 8 million analysis results records.
8.
How long does the QbD1200 UV lamp last?
The UV lamp will typically last >12months, supporting an annual service and calibration interval.
The UV lamp health is essential to the TOC analysis. The UV lamp is only turned on during the oxidation
section of each water sample TOC analysis. The QbD1200 tests the UV lamp functionality on power on and
this check can be initiated at any time by the user using the QbD1200 menu. In addition, the QbD1200
monitors the intensity of the UV light emitted every time it is switched on. If at any time the QbD1200
detects that the UV intensity is not strong enough, or that the UV lamp has failed to turn on when
instructed to do so, then the QbD1200 stops trying to analyze the water samples and sets an alarm
notification on the front screen.
9.
Can I connect the QbD1200 to a networked printer over Ethernet?
No. The QbD1200 is designed to provide paperless electronic records via USB or over secure FTP using
Ethernet. It can also provide printed paper records via USB-connected printer. The internal memory in the
QbD1200 is 21 CFR part 11 secure and can retain approximately 8 million analysis results records.
10. Can I connect a keyboard and a mouse to the QbD1200?
Yes. The QbD1200 has a touch-screen interface and on-screen keyboard appears when there is a need to
type information in. However, both an external mouse and keyboard can be connected to the QbD1200 if
desired.
11. What is the service and calibration interval for the QbD1200?
The service interval for the QbD1200 is 12 months. The QbD1200 continuously monitors all critical
parameters and stops analysis and reports an on-screen alarm should any critical parameter fail, i.e. the
QbD1200 continuously monitors: UV light intensity, reagent, carrier gas, NDIR performance, peltier cooler
and syringe pump.
12. How much TOC is allowable in the water used to make up the One Reagent?
The One Reagent should be diluted for use in the QbD using water with <100ppb TOC. However, the actual
amount of TOC may vary as each new bottle of diluted reagent is made up. The QbD1200 eliminates the
measurement error that this may introduce by having a ‘Background Measurement’ feature, which should
be used every time to allow the QbD1200 to determine the amount of TOC in the freshly made-up diluted
reagent. It can be run again at any time if the user is concerned that the diluted reagent has been sitting in
the bottle for a long time.
13. How does the QbD1200 avoid interference from residual trace amounts of CO2 from the last
measurement?
Before each measurement, the base-line starting point for the measurement in the NDIR detector is
established so that any residual CO2 in the NDIR can be eliminated from the TOC measurement.
14. How many vials can I analyze with 1litre of diluted One Reagent?
If the analyzer is configured to not run an auto-range (i.e. the water samples are known to never contain
>4ppm TOC, e.g. PW or WFI samples) and take just three samples per vial, then the QbD1200 will use just
11mL of diluted One Reagent to analyze each vial. In this configuration, one bottle of diluted One Reagent
will analyze 90 vials.
15. How many vials can I analyze with 1 bottle of the One Reagent stock solution (undiluted)?
To make up a bottle of diluted One Reagent for use with the QbD1200 10mL of the concentrate stock
solution is diluted to make 1Litre. You can analyze 90 vials with 1Litre of the diluted One Reagent, if not
configured for auto-range and only three replications per vial. So you can analyze up to 4,500 vials with
500mL of concentrated One Reagent stock solution.
16. How much carrier gas is used to sample 1 vial?
Assuming a carrier gas flow-rate of 200mL/minute, three reps/vial and an analysis time per rep of circa
3minutes, then each vial will consume in the order of 2Litres of carrier gas. The cost of carrier gas will vary
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according to the source, but, assuming a cost for the carrier gas of €2.50/m *(equals 1,000Litres), then the
cost of the carrier gas is approximately 0.5cents/vial. (*this is a typical cost for bottled gas. The cost of
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carrier gas from a gas generator can be as little as €0.01/m )