Cyclertest Brochure

TOOLS FOR VALIDATION OF (q)PCR THERMAL CYCLERS AND INCUBATORS
DRIFTCON® MTAS® DRIFTCON® RF

Introduction
Cycler Validation Equipment…How it started
It was that unique meeting way back in 1994, when our management team decided to compose a new project-team, that had as goal to develop
an instrument for monitoring temperature performances of thermal cyclers. At that time it was clear that we had to start from scratch since there
was no industrial reference available. The basis for this development choice was founded on the awareness of two major issues as being: first the
fact that there were a number problems occurring in PCR without proper explanation and, secondly the knowledge that PCR would rapidly become
a diagnostic tool.
These basic thoughts and the ongoing development over the last 12 year has resulted in the most sophisticated thermal cycler validation tools
currently available. The tools are widely used in the global marketplace. Surprisingly enough the availability and the intensive use of these tools
enabled the solid, stable, and ongoing incorporation of PCR and qPCR techniques into the diagnostic market place.
It goes without saying that we are permanently challenged to improve our systems to the highest possible technological standards.
Why? We feel we do obligate it to the scientific and diagnostic world.
Tom Hendrikx
CEO President
We present….
In this brochure we present systems and services for validating, calibrating and certifying thermal cyclers. Beside the theoretical issues of validation
we also present, for illustration and educational reasons, real global market data of variables in (q)PCR equipment as well as population variation
data of (q)PCR cyclers of one brand and type. All of our instruments and its outcomes do fully cover any demanded requirements, and do comply
with regulations set by ISO, GLP, GMP, FDA, ILAC, ASHI, CAP, EFI, NY-State, Bell-test and other norms and regulations.
The available systems are:

MTAS® Validation, Calibration and Certification Service (available as service).
DRIFTCON®, a personal temperature drift monitoring system for thermal cyclers and instruments. DRIFTCON is, next to the MTAS® certification,
®
the ideal tool to serve as a periodic and continuous validation instrument for your PCR tests. It also offers a convenient and easy means to check if
your test is still working within its predetermined parameters.
DRIFTCON® RF, a personal wireless drift monitoring system for thermal cyclers and instruments. DRIFTCON ®
RF is typically used in cyclers which
do not allow access to the reaction block by a regular DRIFTCON unit.
®
W e b s i t e : w w w . d r i f t c o n . c o m • E - m a i l : i n f o @ d r i f t c o n . c o m
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W e b s i t e : w w w . c y c l e r t e s t . c o m • E - m a i l : i n f o @ c y c l e r t e s t . c o m
Contents
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1. A tool that makes your (q) PCR transparent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2. Why thermal cyclers are not always accurate & uniform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3. Differences between PCR thermal cyclers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
4. What is measured? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
5. Cycler Performance: the global picture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
6. Regulations and Requirements for Validation and Certification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7. Why different products were developed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
8. Validation and Calibration Service . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
9. End-user systems DRIFTCON® and DRIFTCON® RF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
10. The DRIFTCON® (RF) software . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
11. User-defined DRIFTCON® applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
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1. A tool that makes your (q)PCR transparent
Quality control, validation, calibration and certification have become important issues in the contemporary laboratory.
For some disciplines, a good standardization of the employed procedures has always been obvious, but for others it was historically not that
evident. In the earlier days molecular biology had always been an area where the methodologies were highly preparative and recipe-wise,
with less awareness for quality control aspects.
Nowadays, driven by the amount of diagnostic applications, as well as the fact that investors like to see results supported by hard evidence,
the consciousness that a good validation and certification is a necessity, has become general practice.
PCR (Polymerase Chain Reaction) and qPCR are the key reactions in the field of molecular biology. Whether these techniques are applied for
research, or for the numerous diagnostic purposes (where decisions must be made based on the outcome of the reaction), (q)PCR is leading the
way. Nevertheless, it remains unclear what contribution the major variables like thermal cyclers, reagents and disposables have on the final results.
Especially, the effect of temperature performance of a thermal cycler has turned out to be substantial. There are many different brands and types of
instruments available, and the market is still expanding. As the thermal performance of the many instruments differs to a great extend, a good
quality control procedure becomes an absolute necessity.
Already many years ago CYCLERtest started out with its research into (q)PCR-related temperature measurements, and the influence of temperature
deviations on the results of the (q)PCR reaction. In 1998 the MTAS® service was introduced in the Benelux market as a means for validation and
certification of the temperature performance of thermal cyclers. In the beginning of 2002 the system was presented globally and in 2003 the first
DRIFTCON® end-user tools were added to complete the range.
Today, CYCLERtest is proud to call itself world leader in the field of "temperature performance testing". It is conspicuous that the expertise gained
with the MTAS® service and DRIFTCON® tools has directed several international developments concerning accreditation and certification of
associations and laboratories.
Independency Statement
CYCLERtest and GENO-tronics, the original developers and designers, are independent and neutral companies. The hardware and software products are verified, accepted and approved by the highest global authorities.
Both companies are obligated to improve and develop, even better and sophisticated, systems to serve the still growing and demanding market place. Although CYCLERtest and GENO-tronics supply a high number of
“manufacturers and players” in the marketplace. They refrain from judging or categorizing (q)PCR equipment, which may directly influence the cycler manufacturers market position. However, the market place, users as well
as cycler manufacturers, will definitively benefit using the outcome and the results of our systems, which leads to improvements in the performance of (q)PCR cyclers to the highest possible levels. By doing so, new sensitive
(diagnostic), and solid tools and applications can be introduced in the market.
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2. Why thermal cyclers are not always accurate & uniform
Thermal cyclers are much more complicated in their design than most users of the instrument can imagine. In general, the design of thermal
cyclers can be divided into two sections. One section takes care of the programming, thermal control, power regulation, sensor processing etc.
The other section can be categorized as the block design. The block itself is a construction of several parts: the actual reaction block, the
temperature sensors, Peltier modules, heaters, sealings, as well as a heat sink etc.. These individual layers are constructed on top of each other and
they form a "sandwich" construction.
A diversity of methods are used to balance the sandwich shrinking and expansion, caused by the wide temperature range of operation, 0-100°C
Influence of the denaturation temperature on enzyme depletion (and reaction yield) caused by generally. Although it is beyond the scope of this brochure to discuss every individual construction item, and the impact of these items on the
enzyme heat inactivation. Standard DNA template was used. PCR protocol: annealing 60°C; 60s,
denaturation 30s. Elongation (extension) at constant time and temperature. performance of a cycler, we will give a brief overview on some of these items and the problems that can occur. Overall one should be more
amazed about the fact that a cycler is uniform and accurate, rather than that a cycler is always OK unless proven different!
The actual reaction block

The block is nothing more than a metal plate (a PCR reaction plate made of metal). The block may have an inconsistent surface and well coating
and is often not very flat. Because of fluctuations and variations in the production of blocks (CNC milling, drilling and coating), there may be
different contact angles for tubes, resulting in temperature uniformity and accuracy problems. Since the block has a low mass it is much more
difficult to balance uniformity.
Example of a sensor position in a reaction block The temperature sensors

There are different types of sensors, used to control the block temperature of the thermal cycler: e.g. thermocouples, RTD's
(resistance temperature detectors), thermistors. They all exhibit different inaccuracies and can become defective.
They could also have bad thermal contact, and be very sensitive to (condensation) liquids. All of these problems may result in temperature
uniformity and accuracy problems, or even malfunction of the cycler.
Peltier modules
Every Peltier module consists of around 50 to 250 individual elements which generate heat or cold. Not every individual module and individual
element generates the same amount of heat. This can easily lead to so-called "hot" and "cold" spots in Peltier modules. Complete sections of the
Four Peltiers positioned in a cycler, of which Individual element in a Peltier module Peltier modules may malfunction, and the limited number of temperature sensors, and so the cyclers, are not capable of recognizing these
the reaction block is removed
problems. Besides that, difference in height of the Peltier modules and elements may cause bad thermal contact to the block and to the heat sink,
resulting in block temperature uniformity and accuracy problems.
Decreased performance in time

Heaters (if additional incorporated) may not heat uniformly. Furthermore, the thermal contact of a heater to the reaction block is sometimes not
even. Heaters as well as Peltier modules and sensors are very sensitive to liquid (condensation during cooling). Electrical and mechanical
components like heaters, Peltier modules, sensors, spring tensions etc. are sensitive to wear. This wear is not always uniform and similar for every
build-in component.
Some samples of thermistors
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3. Differences between PCR thermal cyclers
As explained before, there is not a pair of thermal cyclers with the same temperature profile. The accuracy of the block temperature can
deviate either positively or negatively from the set temperature, and the different wells in a block sometimes show a spread (non-uniformity) in
temperature up to several degrees °C. The lack of temperature control in some cyclers causes an occurrence of temperature over- and
undershoots, while trying to reach a plateau.
A first explanation of these differences might be found in the differences in technology. There are many ways to regulate the temperature in a
thermal cycler and to bring and hold the block at a certain temperature. Every technology has its pros and cons. The level to which these
technologies are controlled is essential for the level of performance, but differs greatly. Most cyclers have only a limited level of temperature
control. Differences between single and multi-sensor control mechanisms are obvious causes for temperature inaccuracies.
Although a PCR instrument is normally lacking, apart from the lid, any mechanical or moving parts, it does not imply that it cannot be subject to
wear and tear. The performance of electronic components deteriorate in time, and an intensive use can reinforce this effect. Failure and wear of
Peltier elements can lead to hot or cold spots in a block. In general, the temperature control mechanisms in thermal cyclers do not recognize the
loss of performance caused by wear and tear, block expansion and shrinking. It is therefore crucial to monitor the temperature performance in
time, in order to be aware of these effects. By the same token, a bad thermal performance is often a strong indicator for upcoming failures and
malfunction of a thermal cycler in the near future.
Several external factors can also influence the temperature performance of the cycler. Probably, the most important external factor is the way in
which the tubes are loaded into the block (where to position them?). As a result of the cycler block sensor position (of a certain instrument), a
specific way of loading the tubes (load-effect) can lead to substantial temperature over-/undershoots, and also block sensor in-accuracies.
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4. What is measured?
During the standard validation protocol (30-95-30-90-50-70-60-30 °C) the following parameters are dynamically measured
- Accuracy
- Uniformity
- Ramp Rates
- Overshoots/undershoots
- Hold time
Accuracy The most important measured parameters are temperature accuracy and uniformity of a (q)PCR thermal cycler block. The accuracy shows the
deviation of block temperature from set temperature, while the uniformity is a measure for the spread of temperature between wells of the same
block. Both parameters depend on the temperature level at which they are determined; the accuracy of a thermal cycler normally decreases at
elevated temperatures, block non-uniformity becomes more severe.
In case the temperature accuracy of a thermal cycler is known to be for example -1.0 °C (this implies that the target temperature is not reached),
one can take this into account while developing and optimizing a protocol. For the parameter of non-uniformity this is much more difficult.
However, the main advantage of a dynamic and multi-channel measurement is that it is possible to check which wells deviate too much, and avoid
the use of these hot or cold wells.
The cycling speed (or ramp rate) of a PCR thermal cycler is an indication of the slopes in between the temperature holds. Differences in ramp rate
can influence the course of the reaction. Some cyclers are fast, but less controllable. The material of which the block is manufactured plays an
important role. Directly related to speed, is the overshoot and undershoot parameter. This is amount the target temperature is exceeded while trying
Uniformity to stabilize at a temperature hold. The only way to visualize this is by means of a fast, frequent and dynamic measurement.
Overshoots/undershoots Hold time

Ramp Rates
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5. Cycler Performance: the global picture
Over the last 12 years we have collected tenths of thousands of measurements and validations from a variety of cyclers and brands all over the world. Every temperature measurement, regardless of which type of thermal
cycling instrument is tested, is performed using a standardized and prescribed temperature protocol. This enables the comparison of the results of every measurement performed and shows if the results of a tested instrument
deviate from the protocol standards.
The following picture is extracted from our global data-base and gives a good indication how thermal cyclers, cycler brand and model vary between each other and within their own population. These real data are, most
likely, the best indicator to support the importance of regular validation of thermal instruments with the correct measurement equipment.
Block Uniformity °C
Statistical Market Values at 95°C
from a known manufacturer and
Model (A) 95% population
boundaries
Accuracy:
93.08 °C < A > 95.12 °C
Uniformity:
1.04 °C < A > 2.94 °C
Accuracy °C
Displayed are mean values of multiple measurements of cyclers. X-axis accuracy in degrees centigrade (°C) achieved after 30 seconds at target (95°C) temperature. Y-axis block uniformity (delta
lowest value-highest value) in degrees centigrade. Bubble size indicates spreads of the population (a larger bubble indicates a higher variation of spread than a smaller bubble). Each dot represents
a certain brand and type of cycler. Displayed results are extracted from our global database
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Variation in performance of one type model and brand Performance comparison between two models of the same brand
Performance variation of one type of instrument of

one brand. Each dot represents a specific instru-
ment at a different location in the world. The box
represents 95% of the population. Mentioned val-
ues were measured at 95 °C and after 30 seconds
when reaching the set temperature. X-axis = uni-
formity, Y-axis = accuracy
Accuracy (°C)
Accuracy (°C)
Performance comparison of two types of instru-

ments of one brand. One instrument type: red
dots, other type: purple dots, both types are from
same manufacturer. Each dot represents a specific
instrument at a different location in the world.
The boxes represent 95% of the population.
Mentioned values were measured at 95 °C and
after 30 seconds when reaching the set tempera-
ture. X-axis = uniformity, Y-axis = accuracy
Uniformity (°C) Uniformity (°C)
Performance variation of one type of instrument

of one brand. Each box represents one set temper-
ature (30-50-60-70-90-95) and the variation of
the population at that temperature after 30 sec-
onds. X-axis = uniformity, Y-axis = ∆ accuracy
(set temperature minus reached temperature).
The boxes represent 95% of the population.
Accuracy (°C)
Accuracy (°C)
Performance increase in time of one type of instru-

ment of one brand. Each box represents a time
frame after reaching set temperature of 95 °C.
(10-20, 15, 25-35, 30, 85-95, 90 seconds)
X-axis = uniformity, Y-axis = accuracy boxes
represent 95% of the population.
Uniformity (°C) Uniformity (°C)
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Application thresholds
PCR applications work within certain threshold parameters. In any particular case one can think about variables in procedures pre, during and post
PCR which may influence the generated result. Negative results can include false positives, negatives, no amplification, etc. Some of these
variables are sample identification, sample extraction, administration, pipetting, reaction vessels, reaction components, cycler performance,
detection, hybridization, probe and melting curve limits.
As an example we have used the same reaction conditions as used in an earlier poster publications “The Impact of the Temperature Performance
of PCR Thermal Cyclers on the Generated Results, and the Obligation for Regular Validation of PCR Thermal Cyclers”. Influence of denaturation temperature on enzyme depletion (and reaction yield) caused by
enzyme heat inactivation. Standard DNA template. Running conditions: annealing 60°C, 60 s,
denaturation 30 seconds at different denaturation temperatures. Cycler block non-uniformities
will have substantial influence on the generated amplification results.
Application Thresholds and Cycler Performance
Based on the above mentioned gel and specific conditions one can conclude that this applica-
tion protocol only gives trustworthy results if the denaturation temperature of every well is within
92 and 96 degrees (30 seconds).
Application thresholds in combination with performance thresholds

(blue triangle) of a population of Type A and B model
(same manufacturer) X-axis block uniformity, Y-axis block temperature
at 95 °C setting and after 30 seconds at plateau.
B
A
Accuracy (°C)
Note that only trustworthy results can be generated if the instrument

performance is within the blue application threshold triangle. In this
case most of the A cyclers will generate good results and most of the
B cyclers will not generate trustworthy results if programmed with
denaturation temperature of 95°C for 30 seconds.
Type A and type B cyclers are two different models of the same
Uniformity (°C)
manufacturer!
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6. Regulations & Requirements for Validation & Certification
Over the last years new laboratory regulations and the necessity for regular validation and calibration are designed by authorities. Depending on
the type of laboratory, regulation and validation requirements may have been fully or partly integrated into the laboratory structure and SOP’s. If
focussed on (q)PCR cyclers we have seen a trend that the regulation requirements are nowadays becoming more detailed and moving away from
general statements as “you have to check your cycler annually” without mentioning how, at which accuracy and at how many well locations.
Furthermore it becomes completely unclear what to do when a (q)PCR cycler fails at the annual test and which strategy to follow with results
generated before the validation test. In other words how far do you have to go back and retrospectively re-generate and analyze your results?
Future regulations will show a trend in increasing the frequency of testing to minimize these issues. DRIFTCON® meets these kind of requirements
already.
General guidelines for validating instruments, as cyclers and incubators can be defined as follows:
A. Perform the test similar to the original assay and in the working range of the instrument
B. Test a sufficient and representative numbers of wells
C. The validation and calibration equipment should be at least 3 times more accurate than the equipment tested
D. Full trace ability to the highest international standard (ITS-90)
E. Compliant with FDA 21CFR part 11
A. Perform the test similar to the original assay and in the working range of the instrument
This implies that for (q)PCR cyclers a dynamic measurement is the way to go, and that a static measurement is simply insufficient and incorrect.
B. Test a sufficient and representative numbers of wells

In other words if one has 96 wells in a reaction block one should at least test on multiple locations (CYCLERtest systems typically use 15 locations).
Some regulations require a temperature check of all well locations which, if the case, can be accomplished by the use of our "all well" systems.
In the following columns we have listed some associations which have requirements for (q)PCR cyclers in place:
CAP (Pathology) New York State (Clinical Diagnostics)

NFSCT (Forensics) AAFS
EFI - ASHI (Immunogenetics) FELASA (Animal Health)
AAVLD (Veterinary) GMP
GLP ISO 17025
ISO 18159 ISO 20836
Food Diagnostics AACC
CPA (Pathology) Other Quality programs
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7. Why different products were developed
CYCLERtest and GENO-tronics have developed a number of products depending on the requirements of the laboratory. The MTAS® and Driftcon®
The most optimal way of
systems differ not only in software, hardware, accuracy and ease of handling but, also in the way they are used.
“being in control"
is to combine DRIFTCON® measurements and
MTAS® Certification Services MTAS®
The MTAS® (Mobile Temperature Acquisition System) is used for temperature validation, calibration, service and certification. Accurate handling
It would be a waste of time if the reason why a temperature
and use of the system requires a qualified CYCLERtest training.
validation was carried out, is only to conform to quality norms and
requirements. The majority of users have experienced unexplainable
problems with their (q)PCR experiment, not related to reaction mix DRIFTCON® and DRIFTCON® RF
components (and variables). Fact is that there is often an undefined
The DRIFTCON® and DRIFTCON® RF are end-user tools. The setup of these highly accurate systems is such that they can be easily used in a
preference for a specific instrument on which "my reaction always
routine laboratory. DRIFTCON® stands for Drift and Control, so control your temperature drift in time. DRIFTCON® was developed with the
works". From our experience, this really seems to be the case; not a
knowledge that the MTAS® service is typically performed annually. However, any validation service done with MTAS® is giving a statement on
pair of thermal cyclers, even identical types of the same brand,
performance at that specific time. It does not guarantee any similar performance for the future. So what to do if a cycler does not pass the annual
shows the same temperature profile. And it is exactly this profile that
MTAS validation? Question yourself: what is and was the result’s reliability of the test from yesterday, last week, last month and when did my cycler
is crucial for the success of the reaction.
start to perform badly? For this reason CYCLERtest developed the DRIFTCON® system. It simply enables users to check the temperature
performance frequently and even, in a number of cases, prior starting (q)PCR reactions. So you are not restricted to an annual test and
DRIFTCON® allows you to verify your thermal cycler performance against the global thermal cycler performance database of the same model and
type of thermal cycler.
Fact in many labs, “I have my favorite (q)PCR cycler since it gives me

nice and good results”
CYCLERtest products make transparent why
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8. Validation and Calibration Service
CYCLERtest services
The CYCLERtest validation and calibration are either carried out on-site, or at the authorized distributor location using the MTAS® system.
The MTAS® system, is calibrated against the ITS-90 standard, NIST traceable and optionally ISO17025 calibrated. The MTAS® validation and
calibration service are accepted by accreditation authorities as a tool for supporting thermal cycler performance. Test results are analyzed and
reported through an automated process, prohibiting any alterations of the acquired sample data. CYCLERtest 's policy is that only trained and
certified technicians are allowed to perform validations and certifications with the MTAS® system.
CYCLERtest reports
CYCLERtest results are presented in a detailed report that is generated automatically. CYCLERtest offers different report formats that differ from
each other with respect to the information presented. Reports range from a compact version (10 pages), a standard version (17 pages) up to an
extended version (23 pages) per cycler block. Conclusions about the test results as well as recommendations for further use of the instrument are
included. Temperature data and layouts are encrypted and cannot be modified. The CYCLERtest service complies with the requirements of GLP,
GMP and other Quality Programs.
Certificate of Thermal Validation

A "Certificate of Thermal Validation" accompanies every test report. This certificate represents the results of the measured and calculated main
parameters of the tested instrument. Notice that there is no "judgement" made whether the instrument performance is superior or inferior; this is left
to the end-users' interpretation and has always to be combined with the temperature robustness of the used applications.
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9. End-user systems DRIFTCON® and DRIFTCON® RF
End-user systems DRIFTCON® and DRIFTCON® RF

The DRIFTCON® and DRIFTCON® RF systems are personal measurement systems. While the MTAS® measurement system is intended to validate,
calibrate and certify the thermal performance of a thermal cycler (e.g. monthly) DRIFTCON® systems provide the opportunity to monitor the
described thermal parameters in time. The major difference between DRIFTCON® and DRIFTCON® RF (wireless) is that DRIFTCON® is typically
used in the majority of cyclers and that DRIFTCON® RF (wireless) is used in those cyclers, which do not allow access to the cycler block while
cycling, so called closed systems. The RF in DRIFTCON® RF stands for Radio Frequency and the RF systems are in general more fragile compared
to the regular DRIFTCON® systems.
Pass or Fail is determined by thresholds. Thresholds are supplied by CYCLERtest and determined from market specs and these thresholds can also
be adjusted in the software to the required values (see also the DRIFTCON® software, thresholds).
DRIFTCON®
The DRIFTCON® system consists of a so-called "probe fixture", a construction in which the thermistors are positioned in a holder, and placed in the
DRIFTCON® probe fixture
thermal reaction block, prior to the measurement. The DRIFTCON® box is the hardware module that process the collected sensor readings, after
which the DRIFTCON® software displays them. Usage of the system is monitored by means of software and the DRIFTCON® smart card hardware.
DRIFTCON® RF
The DRIFTCON® RF system consists of a so-called "probe fixture RF", a compact construction in which the thermistors are positioned in a holder,
with the dimensions of a PCR plate. The fixture also contains all processing electronics, calibration values, power cells, as well as RF
communication electronics. The DRIFTCON® RF systems can be used by any closed (q)PCR system (see compatibility chart page 26). While
cycling, all temperature values are transmitted to the supplied RF USB dongle connected to the computer. Usage of the system is monitored by
means of software and the DRIFTCON® RF intelligent hardware.
DRIFTCON® RF probe fixture DRIFTCON® and DRIFTCON® RF test results are analyzed and reported through an automated process, thereby minimizing user intervention and
prohibiting any alteration of the acquired sample data.
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DRIFTCON® monitoring parameters in time

Every temperature measurement, regardless of which type of thermal cycling instrument is tested, is performed preferably using a standardized and
prescribed temperature protocol. This enables the comparison of the results of every measurement performed, and shows if the results of the tested
instrument deviate from the protocol standards. This standard protocol is designed to support all relevant temperatures related to instrument
specifications and the (q)PCR processes. Data and results of the measurements are collected in a central database at CYCLERtest and the
instrument specific market performance is calculated. The market performance can differ from the cycler manufacturer specifications. DRIFTCON®
users can also participate in a global database network generated by CYCLERtest. Particularly, users can determine how their instrument behaves
in terms of accuracy, uniformity as well as temperature drift-in time in comparison to the other users of the same cycler type and brand (globally),
who also participate in the database.
DRIFTCON® hardware module
DRIFTCON® System Components Available in the following configurations:
* DRIFTCON® hardware module + Connection cable o 96V-15: 15 sensors for 96 x 0.2 ml block formats
* Intelligent probe fixture o 16-6: 16 sensors for ALL WELL measurements (NY-State) in 96 x 0.2 ml block formats
* Probe fixture storage box o 48V-12R: 12 sensors for 48 x 0.2ml block formats
* DRIFTCON® SMART-card o 384-15: 15 sensors for 384 block formats
* DRIFTCON® software o 16-24: 16 sensors for ALL WELL measurements (NY-State) in 384 block formats
* Instrument specification set (market specs) o LightCycler®: 16 sensors in capillaries, positioned in LightCycler® Rotor fixture
* Membership of the CYCLERtest global threshold o SmartCyclerTM: 16 sensors in SmartCyclerTM Cuvettes
specification center o Flex 0.2 (flex system): 16 flexible sensors for 0.2 ml tube shape blocks
* DRIFTCON® system storage case o Flex 0.5 (flex system): 16 flexible sensors for 0.5 ml tube shape blocks
* Optional: o Flex 384 (flex system): 16 flexible sensors for 384 wells tube shape blocks DRIFTCON® ALL WELL probe fixture
- cycler software specification sets for
other types/brands of thermal cyclers
- notebook with DRIFTCON® software pre-installed
DRIFTCON® individual probe sensor DRIFTCON® SmartCyclerTM probe fixture DRIFTCON® LightCycler® probe fixture
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DRIFTCON RF® System Components

* DRIFTCON® RF intelligent fixture, electronics and wireless communicator incorporated in the fixture, include also heated lid measurement sensors
* DRIFTCON® RF USB dongle, and extension cable
* DRIFTCON® RF software
* Instrument specification set (market specs)
* Membership of the CYCLERtest global threshold specification center
* DRIFTCON® system storage case
* Optional:
- cycler software specification sets for other types/brands of thermal cyclers
- notebook with DRIFTCON® RF software pre-installed
Available in the following configurations:
o 96V-15: 15 sensors, for 96 x 0.2 ml block format

o 16-6: 16 sensors, for ALL WELL measurements (NY-State) in 96 x 0.2 ml block format
o 96V-15LP: 15 sensors, for low profile 96 x 0.2ml block format
o 16-6LP: 16 sensors , for ALL WELL measurements (NY-State) in low profile 96 x 0.2 ml block format
o 384-15: 15 sensors for 384 block formats
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10. The DRIFTCON®(RF) software
After start up of the DRIFTCON® software a pop-up window shows the thermal cyclers to be measured. The cyclers whose turn it is to be validated
are displayed in red. After selection of an instrument the user proceeds to the main screen, where one can choose from different options, or start a
DRIFTCON® measurement sequence.
Instrument management, (q)PCR Cyclers and Incubators

The properties of the thermal cyclers and incubators that need to be checked regularly in your lab, can be added or edited, and the measurement
frequency (daily, weekly etc.) can be defined from this menu.
Measurement history
The results of every measurement performed are stored, and can be reviewed easily. Relevant basic information concerning the thermal cycler,
DRIFTCON®, user, protocol and external parameters can be displayed, as well as a detailed overview of all the measured parameters: accuracy,
spread, ramp rates, maximum over/undershoot, average over/undershoot and hold (plateau) time.
The two most important parameters, temperature spread and accuracy are presented at six different time points or time intervals (10-20s, 15s,
25-35s, 30s, 85-95s, 90s). At every level the measured and processed values are compared to the threshold values, judged right or wrong
(within or outside the threshold range ).
Graphical views
The temperature uniformity and accuracy can also be presented in a time-graph. With this graph one can visually follow (the development of
performance) of an instrument in time, between set limits (thresholds). By moving the cursor over the graph, exact values are displayed. A more
advanced option in drift overview can also be displayed. The advanced option enables overviews and comparisons of brands, models, block types,
block layouts, temperatures, time sets, for all variables measured as accuracy, uniformity, hold time, ramp rates, over/undershoots, drift and
selected specification sets.
17
“Movie” player
Any temperature acquisition can be replayed using the “movie” player. The “movie” player can be opened for two different acquisitions which
allow temperature and cycler comparison at any temperature and required channels to be monitored at any time in the cycling process.
The “movie” player is presented in a way that one has a clear view of the block and the temperature of the block, including the hot and cold
spots are indicated in color. Furthermore all relevant parameters are dynamically displayed.
Replay mode for detecting optimal control position

The “movie” player is an ideal tool to help to optimize your control position basically drilled down to the performance of that individual (q)PCR
cycler.
Reporting capabilities
A nine page report of each measurement can automatically be generated. In these reports all relevant data as well as individual channel
values are listed. Different report layouts also can be selected. Next to that, a wide variety of drift reports can be generated from either one
instrument, one type of instrument or all types of instruments, one type of block or all type of blocks, with a free selection of any of the
variables as accuracy, at which time, uniformity, heat rate, cool rate, plateau, drift, selected specification sets etc.
18
Pass or fail criteria

Pass or fail is depending on the selected thresholds. There are two options when it comes to thresholds: (1) choosing to compare to the
market specifications (the average worldwide performance of a certain brand and type of cycler), or better, (2) empirically determine the
limits of a certain test (e.g. a HIV detection), and set the found values as pre-determined thresholds. The pro-active dynamic threshold
database is accessible and automatically loaded by using the synchronize button. In other words, the software features fully automated
synchronization functionality of market specs.
Instrument-based thresholds (market specs)

Instrument thresholds (the average market performance for one specific instrument and block type) are provided with the purchase of any
DRIFTCON® and DRIFTCON® RF system. Other brand/block-type specific threshold settings may be purchased as software "add-on"
(optional). These specific instrument thresholds are extracted from the global CYCLERtest database, which contains numerous measurements
of machines of that same brand and type. These values are provided as a mean plus or minus 1.96 x the standard deviation representing
95% of the population.
Application-based thresholds
Although the design of the application thresholds is much more difficult and time-consuming, application thresholds are superior to
instrument thresholds. In other words: application thresholds offer a real view whether or not the used cycler is suitable for this application.
In case of a commercial (diagnostic) kit (PCR, LCR, qPCR, RT-PCR etc) one may request the temperature profile thresholds from the kit
manufacturer. Should the kit manufacturer not have these thresholds available, then it's worth visiting or participating in our discussion forum
on the DRIFTCON® website: www.driftcon.com
User management
Three user levels can be defined: Administrator, Controller, and User. The Administrator has full access to all possibilities of the software.
This person can create other users and change their settings, set threshold values and alter other controls. The Controller is not able to do
this, but can add and edit instruments. A User is just able to perform measurements and view results only.
Synchronization of results
To be able to judge the DRIFTCON® results versus a frame of reference, it is possible to exchange measurement data with the CYCLERtest
database. In exchange of these values access is granted to the most up-to-date market specifications of the brand and type of instrument
used.
19
11. User-defined DRIFTCON® applications
Typical users of the DRIFTCON® and DRIFTCON® RF systems

1. Quality managers of laboratories 4. PCR end users (research) 7. Inspectors, auditors and other regulatory officials
2. PCR kit manufacturers 5. Thermal cycler manufacturers 8. Purchase officers
3. PCR end users (diagnostics) 6. Technical service departments 9. Users of a Real-Time PCR thermal cycler
1. Quality Manager Laboratory

The quality manager is responsible for all the standardization and quality issues in the laboratory. DRIFTCON® enables the quality manager to
design the regulatory requirements for thermal cyclers and applications used. Typically, the quality manager has access to DRIFTCON® at the
administrator level. DRIFTCON® allows the quality manager to have full access to the user management system, overall system settings and device
management. Besides that the quality manager has full access to the trace ability and report options in the software.
The quality manager has the possibility to set instrument and application thresholds into detail. These settings may then be used to determine if
the tested instrument is performing within specifications. The quality manager also decides on the test frequency of the PCR equipment, and sets
clear definitions whether the threshold preferences are based on application(s) or on instruments.
2. PCR Kit Manufacturers

These manufacturers provide PCR kits to different markets. Most of these kits are designed to work on one or a few brands and types of cyclers.
In general, manufacturers recommend that their kit is used in combination with the cycler brand on which it was developed. Typically, when kit
manufacturers get claims from customers that their kit is not always working well, they cannot reproduce the customer’s findings in their QC lab,
due to the difference in cycler temperature performance. Kit manufacturers may opt or require to measure customers thermal (q)PCR cycler to rule
out possible cycler related issues from the kit.
The use of DRIFTCON® in developing, improving and marketing PCR kits

PCR kit manufacturers can use DRIFTCON® to determine the optimum temperature profile of their PCR kit. With DRIFTCON® one can set
thresholds for temperature accuracy and block non-uniformity (spread) within which a kit functions. In other words: determining the maximum
temperature in-accuracy and spread still allowing the generation of a reliable result. Kit manufacturers may consider separating accuracy and
spread settings. Different protocols for the same kit may be advised depending on the dynamic temperature performance (DRIFTCON® driven)
of the customer’s thermal cycler.
Users of commercial kits can request their kit supplier to provide prescribed threshold sets for temperature accuracy and required block uniformity
of the kit and/or cycler.
20
3. PCR End-users (diagnostics)

This type of end-user generates diagnostic results and supports these results with appropriate evidence like biological controls, and assurance of
full trace ability and quality performance of the used equipment. Depending on the internal validation schedule, the type of investigations, and the
impact and importance of the generated result, they should typically use DRIFTCON® on a daily, weekly or monthly base, and trace the drift of
temperature performance of the cycler in time. The kit manufacturer may strongly recommend the use of DRIFTCON®. With DRIFTCON® a decision
can be made whether a cycler is suited to be used for a certain application.
Determine your control positions on the cycler

To generate a trustworthy result every run contains several known controls. Extra security and support of your results can be achieved by determing
the hottest and coldest area in your cyclers block. The areas can be easily extracted from the data file using the “movie” player of the DRIFTCON®
system.
Non-working kits; kit claims

Your kit manufacturer may recommend the regular use of a DRIFTCON® system to exclude variations in results, generated by a lack of
performance of the used cycler. A kit manufacturer may even require seeing the thermal DRIFTCON® profile of the used cycler prior to the
acceptance of kit claims.
Non-working instruments or “out of specs” instruments

Instruments may be performing out of “instruments market specs” provided by CYCLERtest. One can request the latest specifications by
synchronizing to the general CYCLERtest database. Be aware that pass and fail are only indicators as far as one uses the “market specs” as
thresholds. Optimal “pass and fail” conditions can be achieved by determination of the specific “application thresholds”.
Temperature threshold settings for a kit (application thresholds)

Users of commercial PCR kits may request kit manufacturers to provide prescribed threshold set(s) for temperature accuracy and block non-
uniformity of the kit and/or cycler. A diagnostic PCR end-user may be requested by governmental auditors and other regulatory bodies to provide
the temperature threshold settings for the supplied kit as well as the actual validation of these data in time (DRIFTCON® driven).
4. PCR End-users (research)

These users are generating experimental results and support these results with appropriate evidence like biological controls. Assurance of full trace
ability is not necessarily required, but quality approval of the used equipment is more than welcome. As a result of the differences in the
experiments, and the experience level of users, they will use DRIFTCON® more as a tool to understand, explain and support differences in the
generated (q)PCR results, based on the temperature performance of cyclers. Brand to brand differences, as well as differences in performance
within the same brand can be monitored and explained. They typically use the outcome of the DRIFTCON® measurements to adjust the
temperature profiles of different cyclers and ensure the generation of similar results on different machines. They could be using the DRIFTCON®
knowledge for future cycler purchases. DRIFTCON® is typically used on a monthly basis.
21

Generate a trustworthy result every run contains several known controls. Extra security and support of your results can be achieved by determing
the hottest and coldest area in your cyclers block. The areas can be easily extracted from the DRIFTCON® validation file using the movie player of
the DRIFTCON® or DRIFTCON® RF system.
5. Cycler Manufacturers and Suppliers

A cycler manufacturer/supplier provides cyclers to the different market place(s). Typically, cycler manufacturers and cycler suppliers get claims from
end users that their cycler is not always working well, although they cannot reproduce the customer’s findings in their test lab. The use of
DRIFTCON® as a final factory release test is therefore strongly recommended. A cycler manufacturer may consider recommending the regular use
of a DRIFTCON® system to end users, to exclude variations in results caused by non cycler related issues (enzymes, primers, disposables, incorrect
programming etc.). At the same time, a cycler manufacturer may consider requesting the DRIFTCON® thermal profile of the used cycler, prior to
acceptance of cycler-performance claims. If you manufacture cyclers for Real-Time applications, the use of DRIFTCON® or DRIFTCON® RF is
strongly recommended.
Use of DRIFTCON® in thermal cycler manufacturing

Cycler manufacturers can use DRIFTCON® or CYCLERtest technology to determine the temperature profile of their cyclers. It can be used as an
“in process control” during the manufacturing of the cycling blocks. DRIFTCON® will recognize minor inaccuracies in the block construction, like
incorrectly placed sensors, non-uniform Peltiers, (so called “hot” and “cold” spots), block sandwich tension problems, heater non-uniformities, etc.
By using DRIFTCON® one can set thresholds towards temperature accuracy and block uniformity of a specific cycler type. In other words: define
what the maximum temperature in-accuracy and block non-uniformity of the cycler is, which can still be acceptable before you categorize it as
being “out of specs”. Cycler manufacturers may consider upgrading their “instrument specs” with data based on high accuracy, dynamic, multi
sensor temperature measurements (DRIFTCON® driven).
Defective instruments or “out of specs” instruments

Your instrument may be performing out of “instruments specs” provided by CYCLERtest. You can request the latest instrument market specifications
by synchronizing to our general database.
22
6. Technical Services Departments

Typically, these departments are responsible for the service and maintenance of instruments in their institute or company. In some cases the
purchase department requests their (technical) advice. They are responsible for handling claims of “not correctly working” or “incorrect” cyclers,
but normally do not have access to highly accurate, multi-sensor and dynamic measurement systems like DRIFTCON®. The use of DRIFTCON®
as a “diagnostic tool” is highly recommended. Technical services departments should consider using a DRIFTCON® system on a regular base to
exclude variations in results generated by a lack of performance of non-cycler related issues (enzymes, primers, protocol, disposables etc.).
If the institute/company has cyclers for real-time applications, the use of DRIFTCON® or DRIFTCON® RF is strongly recommended.
In a number of cases these departments may consider to qualify for a sub-license of MTAS®-service systems.
Use of DRIFTCON® in service departments

DRIFTCON® should be used to determine the temperature profile of the cycler. DRIFTCON® will recognize minor inaccuracies in the block
construction, like incorrectly placed sensors, non- uniform Peltiers (so called “hot” and “cold” spots), block sandwich tension problems, heater non-
uniformities etc. as well as wearing and drift problems in time. By using DRIFTCON® one can set thresholds for temperature accuracy and block
uniformity of the specific cycler type. In other words: define what the maximum temperature in-accuracy and block non-uniformity of the cycler is,
which can still be accepted before it is categorized as being “out of specs”. Service departments may consider upgrading their “instrument specs”
Positioning the DRIFTCON® probe fixture in a PCR block with data based on high accuracy, dynamic, multi sensor temperature measurements (DRIFTCON® driven).
Incoming quality control

In institutes/companies, DRIFTCON® might serve as an incoming quality control tool for newly purchased regular and Real-Time thermal cyclers.
It is a way to accept or reject instruments, based on the proof provided by DRIFTCON® measurements.
7. Inspectors, Authorized Auditors and other Regulatory Officials

Inspectors, authorized auditors and other regulatory officials are investigating and certifying quality issues in laboratories. They expect hard
evidence from the audited laboratory, since they have to comply to certain regulations, like GMP, GLP, ISO, FDA and others. DRIFTCON® has been
designed in such a way that an inspector can design or even advice in the regulatory requirements for thermal cyclers, and the used PCR
applications in a lab or department. The inspector should have access to DRIFTCON® at the administrator level. DRIFTCON® allows the
administrator full access to the user management system, overall system settings and device management. Besides that, the inspector has full
access to the trace ability and report options in the software. The software and hardware are compliant with FDA regulations (part 21 CFR part
11).
Drift of instruments or applications in time

Using the report button one can display drift of temperature and uniformity. All tested temperatures and times can be displayed and printed.
Generally, we recommend targeting the higher temperatures (90 and 95°C), and to different time points and scales.
Reporting thresholds
The thresholds displayed are the ones that are used during the actual measurements. Any changes in thresholds are displayed in the report.
23
8. Purchase Officers
Purchase officers of (q)PCR thermal cyclers and (q)PCR related kits are responsible for the purchase of medium to high capital equipment.
They are keen to optimize the balance between quality, price and reliability. And therefore they are always searching for tools that can help in
finding that balance. Besides using these tools they are communicating and fine-tuning their judgment with the end-users’ department and possibly
with the technical service department of their institute.
Cycler demonstrations
Requesting a DRIFTCON® temperature profile (temperature performance) from the end-user might be considered, to support the purchase of a
specific cycler. Depending on the individual situation the technical service department may be asked to advice with the DRIFTCON® temperature
profile. Profiles can be requested for all tested cyclers and support the purchase with the provided temperature profiles.
Incoming Quality Control

In the institute/company, DRIFTCON® and DRIFTCON® RF might serve as an incoming quality control tool, for newly purchased regular and
Real-Time thermal cyclers. It is a way to accept or reject instruments, based on the results provided by DRIFTCON® or DRIFTCON® RF
measurements, and to advice the accounting department on the payment release for the equipment.
Purchase of (diagnostics) PCR kits

Users of commercial PCR kits may request kit manufacturers to provide prescribed threshold set(s) for temperature accuracy and block uniformity of
the kit and/or cycler. A kit manufacturer may be requested by governmental auditors and other regulatory bodies to provide the temperature
threshold settings for the supplied kit as well as the actual validation of these data in time (DRIFTCON® and DRIFTCON® RF driven).
9. Users of a Real-Time PCR Thermal Cycler

Users of a Real-Time PCR thermal cycler are generating Real-Time PCR (diagnostic) results and would like to support these results with appropriate
evidence like biological controls, and assurance of full trace ability and quality of the used equipment. We therefore strongly recommend the use Where would you put your controls in this qPCR cycler?
of DRIFTCON® or DRIFTCON® RF for Real-Time applications. Depending on the internal validation schedule, the type of investigations, and the
impact and importance of the generated results, one should typically use DRIFTCON® on a daily, weekly or monthly base, and trace the drift of
temperature performance of a cycler in time. The kit manufacturer may strongly recommend the use of DRIFTCON®. With DRIFTCON® one can
test if the cycler suitable to run your application.

To generate a trustworthy result every run contains several known controls. Extra security and support of your results can be achieved by determing
the hottest and coldest area in your cyclers block. The areas can be easily extracted from the DRIFTCON® validation file using the “movie” player
of the DRIFTCON® or DRIFTCON® RF system.
24
Block non-uniformities
Every thermal cycler has temperature non-uniformities. Be aware of the fact that you may have individual “hot” and “cold” spots in the reaction
block. These spots are normally not detected or not early enough with biological controls, or by the use of internal sample controls. In that respect
it is important to realize that the results of fluorescence signal, yield and melting curves are in direct relation with these temperatures. If, e.g. the
difference would just be 1°C, the impact on the generated yield and fluorescence signal would already be enormous.
Non-working kits, kit claims

The kit manufacturer may recommend the regular use of a DRIFTCON® system to exclude variations in results, generated by a lack of thermal
performance of the used cycler. A kit manufacturer may even require studying the thermal DRIFTCON® profile of the used cycler prior to the
acceptance of kit claims.
Non-working instruments or “out of specs” instruments

The instrument may be performing out of “instruments specs” provided by CYCLERtest. One can obtain the latest specifications by synchronizing to
the general CYCLERtest database.
Temperature threshold settings for a kit

Users of commercially available kits may request kit manufacturers to provide prescribed threshold set(s) for temperature accuracy and block
uniformity of the kit and/or cycler. Governmental auditors may request a kit manufacturer and other regulatory bodies to provide the temperature
threshold setting for the supplied kit as well as the actual validation of these data in time (DRIFTCON® driven).
Melting curve accuracy

In qPCR procedures fragment identification and size are often determined using a so called “melting” curve. Validation and knowledge of the
accuracy and uniformity of the block at melting curve temperatures are helpful tools to support the generated results.
DRIFTCON® “movie” player
25
Which cycler models can be measured?

Basically any (q)PCR cycler and dry-block incubator can be measured. Furthermore non related “block cyclers”
as LightCycler®, SmartCycler®, COBAS®, TaqMan® and so called Fast and closed systems can be measured and
validated. Contact CYCLERtest or an authorized distributor for advice for which type and configuration of
DRIFTCON® or DRIFTCON® RF is most appropriate to measure your instrument range.
MTAS® Service
All (97%) existing brands and types of cyclers including Real-Time cyclers.
End-user Systems
Manufacturer Regular Cycler Model System Manufacturer Real-Time Cycler Model System
Applied Biosystems 240, 2400, 2700, 2720, 9600, 9700, 9800 Fast Driftcon® Applied Biosystems 5700, 7000, 7700 Driftcon®
Applied Biosystems 7300, 7500, 7900HT Driftcon® RF
Bioer XP, Genius, Life Express Driftcon®
Bio-Rad iCyclerTM, iQTM5, my iQTM Driftcon®
Biometra Uno, Uno II, Tpersonal, T1, Tgradient, T3, Tprofessional, TRobot Driftcon®
Bio-Rad, MJ Research type Opticon 1, Opticon 2, MiniOpticon , Chromo 4
TM TM TM TM
Driftcon®
Bio-Rad Gene-Cycler®, iCycler®, MyCycler® Driftcon®
Cepheid SmartCycler® Driftcon®
Bio-Rad, MJ Research type PTC®-100, 150, 200, 220, 221, 225 Driftcon®
Eppendorf MasterCycler® ep, realplex® Driftcon® RF
Corbett Research Palm-CyclerTM Driftcon®
Evogen EvocyclerTM Driftcon®
Eppendorf Mastercycler®, all types Driftcon®
Roche LightCycler® 480 Driftcon® RF

Finnzymes all types Driftcon®
Roche LightCycler® 1, LightCycler® 2, COBAS® Taqman® Driftcon®
GRI G-storm , all types
TM
Driftcon
®
Stratagene Mx3000P®, Mx3005P® Driftcon® (RF)

MWG all types Driftcon®
Techne Quantica® Driftcon®
Takara all types Driftcon®
Techne all types Driftcon®
Contact CYCLERtest or a CYCLERtest authorized distibutor for exact system configuration.
26
CYCLERtest service (using the MTAS® system) DRIFTCON® end-user product DRIFTCON® RF end-user product
It is offered as a service on-site, as well as in house (at the authorized Use is recommended daily, weekly or monthly Use is recommended daily, weekly or monthly
distributor's location). It is recommended every year, or after every 250
runs (whichever comes first). o Measurements are performed dynamically o Measurements are performed dynamically
o Measurements on virtually all thermal equipment, regardless brand or type o Measurements on all (q) PCR closed systems non accessible by regular
o Measurements are performed dynamically, static and dynamic results are reported o Measurements are traceable to the ITS-90 Scale DRIFTCON systems, regardless brand or type
o Measurements on virtually all thermal equipment, regardless of brand or type o Measurements and test systems are NIST traceable o Measurements are traceable to the ITS-90 Scale
o Measurements are traceable to the ITS-90 Scale o System Accuracy is better than ±0.15°C over a range of 10 - 100°C o Measurements and test systems are NIST traceable
o Measurements and test systems are NIST traceable o Measurement range 10-100°C o System accuracy is better than ±0.20°C over a range of 10 - 100°C
o System accuracy is better than ±0.1°C over a range of 10 - 100°C o Measurements of up to 16 channels simultaneously (2 Hz/channel) o Measurement range 5-100°C
o Measurement range 10 - 100°C o Retrospective analysis, and movie player in place o Measurements of up to 16 channels simultaneously (2 Hz/channel)
o Measurements of 16 or more channels simultaneously (2 Hz/channel) o Test reports of drift, uniformity and accuracy, heat rate, cool rate, hold time o Retrospective analysis, and movie player in place
o Test reports in 3 possible configurations + additional custom reporting o Access to global DRIFTCON® database o Test reports of drift, uniformity and accuracy, ramp rate, cool rate, hold time
o "Certificate of Thermal Validation" for the instruments o Cycler to cycler protocol transition tool o Access to global DRIFTCON® database
o Adjustment of the device if possible and necessary o Conform GMP, GLP, ISO, RvA, governmental and association regulations o Cycler to cycler protocol transition tool
o Conclusions and recommendations regarding the use of the device o Conform GMP, GLP, ISO, RvA, governmental and association regulations
o Cycler to cycler protocol transition service available
o ISO 17025 calibration optional
DRIFTCON® MTAS®-16 DRIFTCON® RF MTAS®-96
Number of sensors 15 16 16 96
Cycler Probe fixture yes yes (optional) wireless yes (optional)
Intelligent Probes yes yes yes yes
Application for end-user service dept* 50+ / dist. end-user distributor service
Trademarks:
Validation yes yes yes yes
CYCLERtest is a trademark of CYCLERtest BV, The Netherlands.
Certification no yes+ no yes GENO-tronics, DRIFTCON and DRIFTCON RF, MTAS are registered trademarks of GENO-tonics, BV The Netherlands.
Cycler type all all (q) PCR close all Evocycler is a trademark of Evogen Ltd.
Purchase option sales lease sales/service lease G-storm is a trademark of Gene Technologies Ltd.
iCycler, iQ5, my iQ,PTC-100, PTC-150, PTC-200, PTC-220, PTC-221, PTC-225 are registered trademark of Bio-Rad Laboratories, Inc.
System accuracy ±0.15 ±0.10 ±0.20 ±0.10 LightCycler is a registered trademark of the Roche Diagnostics GmbH.
Mastercycler is a registered trademark of Eppendorf AG.
Drift overviews yes no yes optional Mx3000P, Mx3005P and Stratagene® are registered trademarks of Stratagene company, USA
Opticon 1, Opticon 2, MiniOpticon, Chromo 4 are trademarks of Bio-Rad Laboratories, Inc.
Accuracy yes yes yes yes Palm-Cycler is a trademark of Corbett Research, Australia.
Uniformity yes yes yes yes SmartCycler is a trademark of Cepheid Inc.
Uno, Uno II, Tpersonal, T1, TGradient, T3, TProfessional, TRobot are (registered) trademarks of Biometra Biomedizinische Analytik GmbH.
Ramp Rates yes yes yes yes Quantica is a registered trademark of Techne Ltd and Techne, Inc.
Over/Undershoots yes yes yes yes GeneAmp is a registered trademark of Roche Molecular Systems Inc.
COBAS is a trademark of a Member of the Roche Group
Hold time yes yes yes yes TaqMan is a registered trademark Applied Biosystems.
Heated lid no no optional optional The PCR (Polymerase Chain Reaction) Process is covered by patents owned by Hoffman-La Roche, Inc. (4.683.195, 4.683.202, 4.965.188).
“Movie” Player yes no yes yes
Performance level + +++ ++ ++++ Copyright CYCLERtest 01-2007. All rights reserved.
Calibration required 1 year 1 year 1 year 1 year
Report options ++ ++++ ++ ++++
ISO 17025 calibration yes / flex set only yes (optional) n/a yes (optional)
near future near future
27
Your local distributor:
CYCLERtest BV Phone: +31+(0)45 533 87 33 BPCTi Inc, Phone: 919 806 8811
Rötscherweg 61, Entrance C Fax: +31+(0)45 533 87 94 2933 South Miami Blvd. Fax: 919 806 2014
6374 XW Landgraaf Website: www.cyclertest.com - www.driftcon.com Suite 121 Website: www.bpcti.com - www.driftcon.com
The Netherlands E-mail: support@cyclertest.com - support@driftcon.com Durham, NC 27703, USA E-mail: info@bpcti.com - support@driftcon.com

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TOOLS FOR VALIDATION OF (q)PCR THERMAL CYCLERS AND INCUBATORS

DRIFTCON® MTAS® DRIFTCON® RF

Cycler Validation Equipment…How it started

The available systems are:

The actual reaction block

Example of a sensor position in a reaction block The temperature sensors

Decreased performance in time

Overshoots/undershoots Hold time

Performance variation of one type of instrument of

Performance comparison of two types of instru-

Uniformity (°C) Uniformity (°C)

Performance variation of one type of instrument

Performance increase in time of one type of instru-

Uniformity (°C) Uniformity (°C)

Application thresholds in combination with performance thresholds

Note that only trustworthy results can be generated if the instrument

B. Test a sufficient and representative numbers of wells

CAP (Pathology) New York State (Clinical Diagnostics)

Fact in many labs, “I have my favorite (q)PCR cycler since it gives me

CYCLERtest products make transparent why

Certificate of Thermal Validation

End-user systems DRIFTCON® and DRIFTCON® RF

DRIFTCON® monitoring parameters in time

DRIFTCON® System Components Available in the following configurations:

DRIFTCON RF® System Components

Available in the following configurations:

o 96V-15: 15 sensors, for 96 x 0.2 ml block format

Instrument management, (q)PCR Cyclers and Incubators

Replay mode for detecting optimal control position

Pass or fail criteria

Instrument-based thresholds (market specs)

Typical users of the DRIFTCON® and DRIFTCON® RF systems

1. Quality Manager Laboratory

2. PCR Kit Manufacturers

The use of DRIFTCON® in developing, improving and marketing PCR kits

3. PCR End-users (diagnostics)

Determine your control positions on the cycler

Non-working kits; kit claims

Non-working instruments or “out of specs” instruments

Temperature threshold settings for a kit (application thresholds)

4. PCR End-users (research)

Determine your control positions on the cycler

5. Cycler Manufacturers and Suppliers

Use of DRIFTCON® in thermal cycler manufacturing

Defective instruments or “out of specs” instruments

6. Technical Services Departments

Use of DRIFTCON® in service departments

Incoming quality control

7. Inspectors, Authorized Auditors and other Regulatory Officials

Drift of instruments or applications in time

Incoming Quality Control

Purchase of (diagnostics) PCR kits

9. Users of a Real-Time PCR Thermal Cycler

Determine your control positions on the cycler

Non-working kits, kit claims

Non-working instruments or “out of specs” instruments

Temperature threshold settings for a kit

Melting curve accuracy

DRIFTCON® “movie” player

Which cycler models can be measured?

Roche LightCycler® 480 Driftcon® RF

Stratagene Mx3000P®, Mx3005P® Driftcon® (RF)

Techne all types Driftcon®

Contact CYCLERtest or a CYCLERtest authorized distibutor for exact system configuration.