TM

PURE WATER
FOR BIOMEDICAL LABORATORIES

Water purification

ADVANCING LIFE SCIENCE TOGETHERTM

Research. Development. Production.
WATER,
ONE OF THE MOST
IMPORTANT REAGENTS

Pure
water
system
Of all the fluidic reagents needed on-board an analyzer, WATER is the most frequently used. Purified water is
employed extensively in biomedical laboratories, in a wide variety of applications ranging from General Chemistry
to Enzyme Immunoassays, including Toxicology, Trace Elements analysis, and Molecular testing assays.
For each assay, different types of contaminants may interfere with the analysis and alter the test results.
Millipore’s long history of collaboration with biomedical laboratories has enabled us to develop our expertise
concerning biomedical applications as well as water contaminants.
The table below provides an overview of the different contaminants that can impact your applications, along with
the water purification technologies able to decrease or eliminate these specific contaminants. The following
pages then discuss this information in greater depth, with the aim of helping you improve efficiency and precision
of results in your lab.

BACTERIA
IONS ORGANICS BACTERIA BY-PRODUCTS PARTICLES SILICA

GENERAL
CHEMISTRY
• •

ENZYMES • • • •
TOXICOLOGY
TDM
• • •
EIA • • • •
TRACE
ELEMENTS • • • •
MOLECULAR
TESTING
• • • •
DIAGNOSTIC
INSTRUMENT • • • • • •

PURIFICATION RO, EDI, IEX resins RO, AC, 0.22 µm filter, UF Filters RO, EDI, IEX resins
185/254 nm UV 254 nm UV, (0.22 µm; RO, UF)
TECHNOLOGIES chemicals

KEY UF: Ultrafiltration

RO: Reverse Osmosis AC: Activated Carbon
EDI: Electrodeionization EIA: Enzyme Immunoassay
IEX resins: Ion-Exchange Resins TDM: Therapeutic Drug Monitoring
 CONTENTS
PAGE 02 BIOMEDICAL ASSAY SENSITIVITY
TO WATER CONTAMINANTS

PAGE 06 IMPACT OF THE NEW CLSI GUIDELINE

PAGE 08 THE ROLE OF PURIFICATION TECHNOLOGIES

IN THE BIOMEDICAL LABORATORY

PAGE 12 PEACE OF MIND,

SERVICE TO MEET YOUR NEEDS

PAGE 13 REFERENCES - GLOSSARY

WATER IS AN ESSENTIAL REAGENT
IN THE BIOMEDICAL LABORATORY, NECESSARY FOR
DELIVERING CONSISTENT, HIGH QUALITY RESULTS,
MAXIMIZING PRODUCTIVITY AND IMPROVING PATIENT
OUTCOMES.

In the biomedical laboratory, there are two important reasons

for selecting a high purity water system:

1 The need to supply the water quality specified by the manufacturer of the
diagnostic instruments, as well as the need to provide the water quality
best suited for the laboratory’s applications

Used in a variety of assays, water is a major reagent in clinical chemistry and immunoassay
testing. Analytical factors linked to water quality should be controlled and optimized
to reduce the number of test failures. Drifting calibrations, high blanks, and patient values
trending towards the high/low end of the assay all can stem from poor water quality,
which then contributes to erroneous patient results.

2 The need to comply with the guideline published by the Clinical and
Laboratory Standards Institute - CLSI®

The final product from the water purification process must ensure accurate
and reproducible results. The CLSI guideline has been written to help ensure the use
of suitable water purity in all laboratories, in order to provide consistent clinical
chemistry and immunoassay results.

Millipore has over 50 years of experience in laboratory
water purification and an installed base of several thousand
water purification systems worldwide. We have the expertise
to be your long-term partner for biomedical laboratory
water purification solutions.
By providing an in-depth look at an important aspect
of a specific function related to your analyzer – water
purification – this booklet will help you ensure consistent
patient results by demonstrating how you can optimize
your processes and also follow the advice of regulatory
agencies. Update your knowledge by reading the
overview of the CLSI guideline (pages 6-7), and also
learn everything you need to know about the specific
contaminants that impact your chemistries and how
related purification technologies can ensure a balanced
approach (benefits vs. limitations) for contaminant
removal.
In order to leverage the benefits of these purification
technologies and minimize their respective limitations,
Millipore systems combine several filtration processes,
as well as a patented, innovative technology that you will
find described in the section beginning on page 8
(“The Role of Purification Technologies in the Biomedical
Laboratory”).
Our scientists hope that the dual approach used here to
explain and propose solutions will make this guide both
meaningful and valuable for your activity.

PURE WATER FOR BIOMEDICAL LABORATORIES 01

 BIOMEDICAL ASSAY
SENSITIVITY TO WATER
CONTAMINANTS
Water impacts biomedical assays in many different ways.
Care should be given to the quality of water selected
and its intended applications. Suitable and properly
maintained water purification solutions can limit
issues linked to water quality in biomedical testing
and the resulting instrument downtime.

Natural water contains five major classes of

APPLICATIONS
contaminants, also present in potable tap water:
inorganic ions; organics; particulates and
colloids; bacteria and their by-products and
dissolved gases. Clinical chemistry applications
shown opposite are affected by different water
contaminants and therefore require specific
and appropriate water purification techniques.
These will be discussed under the heading
“The Role of Purification Technologies
in the Biomedical Laboratory.”
Working closely together with our customers
and their applications has allowed us to identify
the contaminants that impact their work and
results on a daily basis.
Two examples are given below:
Example 1: General chemistry assays
The calcium assay has long been one of the
assays generating the most issues in clinical
chemistry. The Arsenazo method, frequently used
to measure calcium, results in the formation of a
colored complex between free calcium and
the Arsenazo reagent. It is also stated, that for
the sampling of serum or blood for calcium,
no complexing agent such as EDTA or oxalic acid
1.
S. Mabic and I. Kano. Clin. Chem. Lab. Med. 2003, 41 (4), 486-491.
• General chemistry, electrolyte, lipid
and protein assays seek to measure ions
(Ca++, K+, Na+, Cl-) and bioorganic molecules
(glucose, amino acids, lipids, etc.), (see
Example 1).
• Enzymology assays measure the
presence and activity of various enzymes
involved in critical biochemical processes.
• Sensitive enzyme immunoassays (EIAs)
provide critical information on biomarkers
and specific disease indicators (cardiology,
thyroid regulation), (see Example 2).
• Toxicology and therapeutic drug
monitoring (TDM) assays are performed
using either immunoassay or
chromatography methods.
• Trace element analysis uses atomic
absorption and ICP-MS to analyze toxic
transition metals (Cr, Mn, Mb, Co) and
heavy metals (Pb, Hg) in occupational
personal monitoring and in case of
disease. The level of other elements very
critical to health (selenium, iodide) can
also be measured.
• Molecular biology techniques like nucleic
acid-binding assays are very valuable
for genetic disease identification and
recognition. Water requirements for these
assays closely resemble those for the
genomics field.1

02 PURE WATER FOR BIOMEDICAL LABORATORIES

should be used as an anticoagulant agent. Finally,
a large portion of the calcium binds with proteins
present in blood, in particular with albumin.
The concentration of the calcium measured is
about 100 mg/l (100 ppm). In purified water,
even with resistivity of only 1 MΩ.cm, the maximum
level of calcium would be 500 µg/l (ppb).
The contribution of the calcium from the water is
thus below 1 % of the concentration of the calcium
measured. Therefore, while the analyte being
measured is an ion, the ionic purity of the water
is not the source of the problems observed with
this assay.
also release small organic acids, a source of
calcium complexing agent, as mentioned above.
Those considerations rationalize the fact that
decontamination of the clinical analyzer, resulting
in a bacteria clearance, often solves the problems
encountered with this assay. It is important to
consider the overall purity of the water, and not
focus on one quality parameter only. Resistivity,
which provides information on the ionic purity of the
water, is important, but it is not sufficient to have a
full view of water purity. Other water quality
parameters must be reviewed and monitored to
ensure a consistent optimum operation of the
clinical analyzer.

Other contaminants potentially present in the

water can bring some light to the subject and
enable us to rationalize the problems. For example,
if the organic level in the water has not been
reduced correctly, small organic acids, including
and similar to oxalic acid, can be present and bind
the calcium, thus reducing the apparent
concentration of calcium. Similarly, amines (similar
in structure to EDTA) may also bind the calcium
ion. Finally, a high bacterial level in the water will
generate the presence of significant levels of
proteins that will complex with the calcium,
therefore leading to an apparently low level
of calcium as well as erroneous values. Bacteria

PURE WATER FOR BIOMEDICAL LABORATORIES 03

 Example 2: Immunoassays
Immunoassays are known to be fairly sensitive.
Optimum experimental and laboratory conditions
are required to perform assays successfully,
and avoid the need for frequent recalibrations,
repeat patient samplings, and increased analyzer
maintenance.
To fully understand the challenges encountered
with these assays, it is useful to consider their
chemistry application and how the quality of
water impacts the method components.
For immunoassays, enzymes released by bacteria,
ions, and organics are classes of contaminants
that can generate issues.
Alkaline phosphatase (ALP) is utilized as a
detection enzyme in many biomedical methods.
These include various enzyme immunoassays,
such as sandwich EIAs and chemiluminescent
immunoassays, ALP-induced biochemical
cascades and ALP-labeled nucleic probes.
In most cases calf ALP is used. However, because
of sequence homology and cross-activity for
many substrates, bacterial ALP can interfere with
the assays using calf ALP. Also, both enzymes use
co-factors (Zn, Mg).
In addition to the enzymes released by the
bacteria, ions may also interfere with these
assays. Ions such as Mg and Zn are cofactors of
the enzymes used in the EIA, while others, such as
Cd and Pb, are enzyme inhibitors. Therefore,
in order to control the level of the cofactors
and avoid the presence of inhibitor ions, it is
important to use water free of ions, i.e., water
with a high resistivity.
Organics at high concentration also may interfere
with EIAs. In particular, charged organics that can
bind to enzyme active sites and form complexes
with the metal cofactor can disturb the catalytic
activity of the reporter enzyme and change the
affinity equilibrium between the antibody and the
antigen.
In conclusion, enzyme immunoassays require high
purity water with low bacteria count, no ALP,
no ions and low organic content.

It has been demonstrated that bacterial species

growing in pure water release ALP. For instance,
in bacterial culture, a 107 cfu/ml concentration of
Caulobacter crescentus released ca 10 µUnit/µl ALP.
Levels of ALP of 10 to 1000 µUnit/µl are sufficient
to generate interferences in the assays used
on clinical analyzers. Therefore, bacterial
proliferation results in interferences with all
clinical assays based on the use of ALP: water
tests, chemiluminescent assays, or biochemical
amplification cascades. A large portion of this ALP
is free, and it flows through 0.2 µm filtration.
Ultrafiltration is an efficient method that can be
used to remove ALP from water and enhance the
reliability of EIAs.

04 PURE WATER FOR BIOMEDICAL LABORATORIES

WATER CONTAMINANTS

InorganicIons
Inorganic ions commonly
present in tap water are
cations, such as sodium,
calcium, magnesium or iron,
and anions, such as bicarbonate,
chloride and sulfate. Many
other ions can be present
depending on the water source. Inorganic ions,
even at trace levels, may affect both organic
and biochemical reactions by acting as
catalysts.
BacteriaandTheirBy-Products
Bacteria contaminate natural
water, especially surface
water. The chlorination
process will ensure removal
of harmful bacteria, but tap
water still contains live
microorganisms. Bacteria
can cause different issues in laboratory
experiments either directly or through their
by-products, such as nucleases or alkaline
phosphatase.

Organics Gases
Dissolved Natural water contains dissolved gases
organic such as nitrogen, oxygen and carbon dioxide.
molecules The concentration of oxygen can affect
present in tap specific biochemical reactions
CO
water are 2
and nitrogen can form bubbles
mainly of O2 that are detrimental to
biological origin. Molecules including humic processes such as particulate
acids, tannins, and lignin are the by-products counting or spectrophotomet-
of the decay of plants. N 2 ric measurements.
However, man-made contaminants may be
introduced by the pipes carrying the water.
For example, PVC pipes may leak their
phthalate esters plasticizers into the water.
Dissolved organics can affect biological
experiments such as cell culture and disturb
analytical techniques. Even moderate organic
contamination present in water used to
prepare liquid chromatography eluents can
cause baseline instability, decrease sensitivity
and resolution and also reduce the column
lifetime.

ParticulatesandColloids
Natural water usually contains
soft particulates (vegetal
debris) and hard particulates
(sand, rock), as well as colloids
that can interfere with
instrument operation.

PURE WATER FOR BIOMEDICAL LABORATORIES 05

 IMPACT
OF THE NEW CLSI
GUIDELINE
The significant role of pure water in all A committee including hospital laboratory
clinical chemistry and immunoassay managers and microbiologists, as well as water
testing means that water-related purification system manufacturers, worked
analytical factors should be monitored to develop the new guideline, which aims to
support clinical laboratories in their efforts
in order to optimize analyzer
to improve their quality system with regard to
performance and provide the best test
water.
results. For a number of years, clinical
laboratory professionals like yourself The classifications formerly used in CLSI/NCCLS
have relied on the Clinical and Laboratory documents to identify types of purified
Standards Institute - CLSI (formerly laboratory water (Type I, II and III) have been
NCCLS)* guideline. replaced in the current guideline with new purity
types that have a greater significance for the
clinical environment.

In 2006, the CLSI issued the newest edition of its

guideline: “Preparation and Testing of Reagent The guideline maintains
Water in the Clinical Laboratory; Approved that it is the user’s
Guideline – Fourth Edition” (CLSI C3-A4).
This new guideline, which is a revised version
responsibility to check
of the 1991 C3-A4 NCCLS document, “provides whether the water used
information on water purity requirements for in the clinical laboratory
clinical laboratory testing, validation of is suitable for the purpose,
specifications, technology available for water
purification, and test procedures to monitor
and defines recommendations
and trend water purity parameters.” 2 for the selection and
validation of water
purification solutions, as
well as system maintenance
2, 3.
Clinical and Laboratory Standards Institute (CLSI). “Preparation and revalidation, and quality
and Testing of Reagent Water in the Clinical Laboratory; Approved
Guideline – Fourth Edition” CLSI document C3-A4 (ISBN 1-56238-610-7). control.
Clinical and Laboratory Standards Institute, 940 West Valley Road,
Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2006.

06 PURE WATER FOR BIOMEDICAL LABORATORIES

The guideline describes the different water
grades that can be found in clinical laboratories.
These include clinical laboratory reagent water
(CLRW)**, which generally can be used in most
applications where Type I or II water was used
previously; special reagent water (SRW),
which may be required for specific applications
(metals analysis, DNA/RNA assays, cell cultures,
immunoassays, etc.) when additional parameter
monitoring is needed to ensure water quality;
and instrument feed water (IFW), whose use is
based on the analyzer equipment manufacturer’s
recommendations.
Users should also note that water that is supplied
by a method manufacturer for use as a diluent or
reagent cannot be substituted for CLRW unless it
meets the appropriate specifications, and that
the suitability of commercially bottled purified
water must be checked before use.
Clinical lab managers and supervisors concerned
about providing the best results from their
immunoassay and clinical chemistry analyzers
need to be aware of the changes concerning
water quality described in the newest version
of the CLSI guideline.

VALIDATION AND TREND MONITORING

Theimportanceofvalidationandtrendmonitoringwith • The guideline provides suggestions concerning

regardtopurifiedwaterandwaterpurificationsystem
performanceintheclinicallab
TheCLSIguidelinealsodiscussesanumberofpoints
concerningvalidationandtrendmonitoring:
• The laboratory should validate the purified water
it intends to use “as fit for purpose”3 before
using it in clinical laboratory testing.
water purification system validation.
• Pure water quality parameters should be
monitored over time and trends noted so that
problems can be corrected before the water
quality becomes an issue. Water used in clinical
analyzers should continue to meet specifications.
• In addition, the document sets out guidelines
concerning ongoing maintenance and
revalidation of water purification systems.

*
Formerly the National Committee on Clinical
Laboratory Standards (NCCLS)
**
This brochure will only address
the characteristics of CLRW.
Know more
The CLSI guideline was developed in the interest
of helping clinical laboratories achieve the most
accurate results. It is both a tool and a reference
guide that can assist you in selecting the most
appropriate solution to meet your laboratory’s
needs. For more information about the CLSI and
the guideline, “Preparation and Testing of Reagent
Water in the Clinical Laboratory; Approved
Guideline – Fourth Edition,” please contact
the CLSI directly or visit their web site:
www.clsi.org

PURE WATER FOR BIOMEDICAL LABORATORIES 07

 THE ROLE OF PURIFICATION
TECHNOLOGIES IN THE
BIOMEDICAL LABORATORY
A combination of purification technologies is used in the biomedical
laboratory setting. This approach allows reduction of contaminant
levels and also ensures that the water dispensed to the clinical
analyzer is of constant quality. Most types of contaminants
are eliminated or removed down to very low levels.

A description of these purification techniques Activated carbon

and the role they play in the biomedical
laboratories follows:
General filtration
General filtration reduces the incoming particle
load, which has two major purposes. One is to
protect downstream water purification
technologies from clogging, and the second
is to protect the clinical analyzer. Indeed,
particulates can clog probes and manifolds
and interfere with spectroscopic detection.
Activated carbon is used to eliminate the oxidative
agents (chlorine, chloramines, fluorine) that are
present in tap water to avoid the development
of microorganisms. It also adsorbs large organic
molecules present in the feed water. Activated
carbon derived from natural products, such as
coconut shell, is typically selected for this
purification step.
Activated carbon is typically used in combination
with other treatment processes. The placement
of carbon in relation to other components is an
important consideration in the design of a water
purification system.

Benefits of general filtration Limitations of carbon filtration

• Effectively removes oxidative agents • Limited capacity due to a high, but limited,
• Decreases the organic load number of binding sites
• Can generate carbon fines
Limitation of general filtration
• Does not efficiently remove ions
and particulates

08 PURE WATER FOR BIOMEDICAL LABORATORIES

Reverse osmosis
Reverse osmosis (RO), a membrane-based
technology that has become a standard
pretreatment technique, is used to decrease the
load of ions, organics, colloids and particulates.
RO membranes are capable of rejecting practically
all particles and bacteria, eliminating
organics > 200 Dalton molecular weight (including
pyrogens) at a level close to 99 %. Ions are
typically eliminated at a level > 95 %.

RO is not a pure filtration process, and in

combination with the filtration action, RO also
involves an ionic exclusion process. For example,
divalent cations are better eliminated than
monovalent cations of similar size. Natural
osmosis occurs when solutions with two different
concentrations are separated by a semi-permeable
membrane. The water dilutes the more concentrated
solution and the end result is an equilibrium.

Osmotic pressure applied to the most concentrated

compartment drives water through the membrane,
which defines the reverse osmosis process (Figure 1).
Salt rejection increases significantly with applied
pressure up to 5 bar.
Because the RO process is based on an equilibrium,
it rejects a percentage of the contaminants.
The quality of RO water, therefore, is susceptible
Figure 1: reverse osmosis
to variations, depending on daily and seasonal
variations in tap water quality.

Benefits of reverse osmosis Limitations of reverse osmosis

• Effectively removes all types of contaminants
to some extent (particles, organics, pyrogens,
microorganisms, colloids and dissolved
inorganics), and is therefore useful as a first
purification step
• Requires minimal maintenance
• Operation parameters (pressure, temperature,
flow rate, ionic rejection) are easy to monitor
• Requires good pretreatment to avoid rapid
membrane damage by water contaminants:
scaling (CaCO3 deposits on the surface),
fouling (deposits of organics or colloids on
the surface) or piercing (RO membrane cut by
hard particulates)
• Water quality can vary depending on daily
and seasonal variation of tap water quality

PURE WATER FOR BIOMEDICAL LABORATORIES 09

 Electrodeionization (EDI)
To obtain a more constant water quality and
eliminate variations, electrodeionization (EDI)
is now included in water purification systems.
EDI removes inorganic ions and charged organics.
Elix electrodeionization is a combination of
electrodialysis and ion-exchange (IEX) resins,
resulting in a process that effectively deionizes
water, while the ion-exchange resins are
continuously regenerated by the electric current
in the unit. This electrochemical regeneration
replaces the chemical regeneration of
conventional ion-exchange techniques.
Millipore’s Elix® module (Figure 2) consists of
a number of “cells” sandwiched between two
electrodes. Cells are separated by a cation-permeable
membrane on one side, and an anion-permeable
membrane on the other. The space in the center
of the cell, between the ion-selective membranes,
is filled with a thin bed of ion-exchange resins to
favor mass transfer.
The ion-exchange resins capture ions in the feed
water. Electric current applied across the module
pulls those ions through the ion-selective
Figure 2: Elix module
Figure 3: Water purification
system combining several
technologies
10 PURE WATER FOR BIOMEDICAL LABORATORIES
Benefits of EDI
• Removes dissolved inorganics and charged
organics effectively, allowing resistivity
above 5 MΩ.cm @ 25 °C to be reached
(which corresponds to a total ionic
contamination level in water of
approximately 50 ppb)
• Environmentally friendly:
self-regenerating process
- No chemical regeneration
- No chemical disposal
- No resin disposal
• Inexpensive to operate: predictable and
economical running costs
membrane towards the electrodes. Cations are
pulled through the cation-permeable membrane
towards the cathode, and anions through the
anion-selective membrane towards the anode.
These ions, however, are unable to travel all the
way to their respective electrodes since they
come to the adjacent ion-selective membrane
which is of the opposite charge. This prevents
further migrations of ions, which are then forced
to concentrate in the space between the cells.
This space is known as the “concentrate” channel,
and the ions concentrated in this area are flushed
out of the system to the drain.
The channel running through the resin bed
in the center of the cell is known as the “dilute”
channel. As water passes down this channel, it is
progressively deionized. Splitting of H2O occurs in
the electric field. This generates H+ and OH-, which
regenerate the ion-exchange resins, effectively
eliminating chemical regeneration.
At this stage in the purification process, water is
stored temporarily in a reservoir. Depending on the
assays, the clinical analyzer and the laboratory, this
water can be used directly to feed the analyzer or
it can be further purified (Figure 3).
Ultrafiltration
One source of interference for enzyme
immunoassays is composed of bacteria and their
by-products. To avoid the presence of bacterial
alkaline phosphatase in the water, some additional
purification techniques targeting this contaminant
can be required, in order to gain more precision
and stability in the assays.
Installed at the outlet of the water system,
the BioPak® C polisher unit is a disposable
ultrafiltration cartridge designed by Millipore.
Its purpose is to minimize alkaline phosphatase
(ALP) released by bacteria that may be present
in analyzer feed water used to dilute reagents,
reconstitute calibrators and controls, and rinse
probes and flush tubing.
The BioPak C cartridge can be installed easily
on most immunoassay and clinical chemistry
analyzers on the market today, providing improved
laboratory efficiency and performance with lower
overall running costs.
The cartridge is composed of polyethersulfone
hollow fibers in a white ABS housing. The BioPak C
ultrafiltration membrane optimizes the rejection
of bacterial alkaline phosphatase (ALP) and bacteria
while maintaining a high flow rate (Figure 4).
Figure 4: Typical impact on a blank
Benefits of the BioPak C ultrafiltration
cartridge
• Produces ALP-free water with bacteria
levels lower than 10 cfu/ml (typically
< 1 cfu/ml)
• Allows stable assay baselines, resulting in
better reliability
• Reduces the need for frequent
analyzer calibration
• Eliminates the need for frequent
decontamination and resulting costly
downtime
• Results warranted within specifications
for 120 days of use
• Maintenance-free
Additional purification techniques
Additional purification used to reach CLRW grade
water involves ion-exchange resins (IEX). High
purity grade resins are selected for their capacity
and their purity. The IEX make ionic bonds, resulting
in very low concentrations of ions in the water:
resistivity after IEX is typically > 18 MΩ.cm.
Bacteria control is key in clinical laboratories,
as bacteria are sources of several kinds of
contaminants (ions, enzymes, organics), and
behave as particulates. It is critical to prevent
extensive bacteria growth and the formation of
biofilm within the equipment. Different strategies
can be combined to maintain low bacterial counts
in water purification systems and clinical analyzers.
Membrane filtration, including 0.22 µm screen
membranes and ultrafiltration membranes, is a
very efficient method for removing bacteria.
Membrane filtration is typically used at the outlet
of the purification process, before water goes
into the clinical analyzers. It ensures a low bacterial
count, < 10 cfu/ml, as required by the CLSI guideline
(for CLRW grade).
Germicidal UV treatment (254 nm wavelength) is
often utilized to prevent bacterial growth within
the purification system and in the intermediary
storage reservoir. In combination with UV treatment,
chemical sanitization (peracetic acid, bleach,
chlorine dioxide) completes the panel of means
to reduce bacterial growth.
PURE WATER FOR BIOMEDICAL LABORATORIES 11
 PEACE OF MIND, SERVICE
TO MEET YOUR NEEDS
Biomedical laboratories are busy and demanding
environments. With throughput for today’s
analyzers often reaching several thousand
samples per day, you need full support to avoid
any interruptions in your purified water supply,
which could jeopardize delivery of test results
to the health professionals and patients who
depend on you.
Professional Support
for Ease-of-Use
Our certified Field Service Support Engineers
provide expert, professional support for the
installation, validation and maintenance of your
water purification systems. Working together
with end-users and appropriate facilities
personnel, they follow a comprehensive
pre-installation checklist to ensure that Millipore
water purification systems are installed
in your laboratory in compliance with
the requirements. We support installation
of both individual water systems and total water
systems, and also offer design and engineering
support for larger volume central systems
requiring pretreatment, storage, and distribution
to multiple points-of-use.
PreventiveMaintenance
Plans for Optimal
Water Quality
When you select a Millipore Service Plan,
you are ensuring a high level of performance
for your organization – as well as complete
peace of mind for yourself. Contact your local
Lab Water Application Specialist to select
one of our pre-defined plans and / or build
your own service solution to match
your needs.
12 PURE WATER FOR BIOMEDICAL LABORATORIES
Among the services provided:
• Preventive maintenance visits
• Program updates
• Maintenance kits
• Customized user training
• Extended system guarantees
• Calibration of monitoring devices
• Storage and distribution loop sanitization
• Pharmacopoeia suitability tests
• Validation support
• Maintenance carried out in a Quality
management system
• Post-installation optimization
• Troubleshooting visits
Qualification Services for Validation
Millipore’s Qualification Program, proposed for
most Millipore systems, covers all the elements
required for the successful qualification of your
Millipore laboratory water systems.
• Millipore water systems are designed for easy
operation within a validated environment.
• Qualification workbooks are provided and
include IQ and OQ protocols, and outline
recommended PQ protocols.
• Millipore Field Service Support Engineers
are trained, certified, and able to conduct
qualification protocols using calibrated equipment.
• Certificates of Conformity, Calibration
and Quality are provided.
REFERENCES
Articles
Bôle J., Mabic S. Utilizing ultrafiltration to remove
alkaline phosphatase from clinical analyzer water.
Clin. Chem. Lab. Med., 44 (5), 603-608, 2006.
Long J., Mabic S. Water quality in patient testing.
Clinical Lab. Prod. 22-23 April, 2007.
Application notes
Water for clinical chemistry. S. Mabic. Millipore
Application Note AB1002EN00.
Bacterial alkaline phosphatase: Relevance,
origin and removal. J. Bôle and S. Mabic.
Millipore Application Note AB1001EN00.

Mabic S. Maintaining water quality in clinical Related documents

chemistry, Advance for Medical Laboratory Mabic S., Kano I. Impact of purified water quality
Professionals, May 2007. on molecular biology experiments. Clin. Chem. Lab.
Med., 41 (4), 486-491, 2003.
Long J., Mabic S. The impact of water quality on
IVD testing. In vitro Diagnostic Technology. 2008 –
In press.

GLOSSARY
Term Definition
Alkaline phosphatase (ALP) Enzyme present in blood; reporter enzyme
used in many immuno enzyme assays and
biochemical cascades.
CFU Colony forming unit; the number of CFUs is
used to represent the microbial content.
CLRW Clinical Laboratory Reagent Water, as defined
by the CLSI.
EDTA Ethylenediaminetetraacetic acid. Coordinates
calcium and other divalent cations.
Electrodeionization (EDI) Self regenerating deionization method based
on the use of a small electrical current applied
to ion-exchange resins.
IFW Instrument Feed Water, as defined by the CLSI.
SRW Special Reagent Water, as defined by the CLSI.
TDM assay Toxicology and therapeutic drug monitoring
assay.
TOC Total Oxidizable Carbon. Expressed in µg/l (or
ppb). It provides an estimate of the overall
amount of organic molecules present in the
water.

PURE WATER FOR BIOMEDICAL LABORATORIES 13

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TM

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ADVANCING LIFE SCIENCE TOGETHERTM

Research. Development. Production.
Lit. No. PB1742EN00. Printed in France 02/09. Copyright © 2009, Millipore Corporation, Billerica, MA, U.S.A. Millipore, Elix and BioPak are registered trademarks
of Millipore Corporation. The M mark and Advancing Life Science Together are trademarks of Millipore Corporation. CLSI is a registered trademark of Clinical and
Laboratory Standards Institute, Inc. All rights reserved. Design: . Photos: Getty, DR.