WATER PURIFICATION. Reference Guide

Transcription

1 WATER PURIFICATION Reference Guide

2 For over 50 years, Millipore has helped improve laboratory productivity and efficiency for researchers worldwide by delivering innovative products and service backed by the highest levels of quality and expertise. With the recent acquisition of Upstate, Chemicon and Linco, we now offer a wide range of antibodies; stem-cell related products; protein immunodetection kits; and drug profiling products and services. The addition of these core products and capabilities to our existing sample preparation and laboratory water offering creates an extensive portfolio of comprehensive solutions for immunodetection, cell biology and drug discovery. As part of our customer-focused approach to support and service, Millipore sales and in-field technical teams receive on-going training in our customers research areas. This training allows them to provide technical assistance, validation services, equipment installation, and maintenance programs for your specific applications. The integrated Millipore offers you more innovative technologies and stronger application support to streamline your progress and give you more confidence in your results. Our lab water experts take the time to evaluate the needs of individual labs and particular applications in order to recommend a system that balances water quality with volume and distribution requirements, removing water quality concerns so customers can focus on their research. We are also developing exciting new web tools to facilitate product selection and on-line ordering. For more information on Millipore water purification solutions, visit To experience all that Millipore has to offer, visit

3 Table of Contents Water Purification Water Contaminants...06 Inorganic Ions...06 Organics Particulates and Colloids Bacteria and their By-products Gases Monitoring of Water Contaminants Resistivity Total Oxidizable Carbon Laboratory Water Types...10 Overview of Water Purification Technologies...11 Distillation...11 Ion Exchange...12 Activated Carbon...14 Microporous Filters...15 Ultrafiltration...16 Reverse Osmosis Elix Continuous Deionization...18 Ultraviolet (UV) Radiation...19 Water Purification Systems Adapted to Specific Needs...20 Pure Water: Type III...22 Technologies Used to Produce Type III Water Pretreatment to Protect the RO Membrane...23 Reverse Osmosis to Purify...23 Type III Water Purification Systems...24 RiOs 3 Water Purification Systems...24 RiOs 5 / 8 / 16 Water Purification Systems...24 RiOs 30 / 50 / 100 / 150 / 200 Water Purification Systems...25 Pure Water: Type II...26 Technologies Used to Produce Type II Water...26 Elix Technology...27 Type II Water Purification Systems...28 Elix 3 / 5 / 10 Water Purification Systems...28 Elix 20 / 35 / 70 / 100 Water Purification Systems...29 Systems for Low Volume Daily Needs...30 RiOs-DI 3 Water Purification Systems...30 Milli-DI Water Purification Systems...31 Solutions for Clinical Analyzers...32 RiOs-DI Clinical Water Purification Systems...32 AFS 3 / 8 / 16 (D) Water Purification Systems...33 Elix Clinical Water Purification Systems...34 BioPak C Polisher...35 Optimized Pure Water Storage , 60 and 100 L PE Reservoirs...36 SDS 200, 350 L Storage and Distribution Systems...36 Automatic Sanitization Module (ASM) and Water Sensor...37 Advanced Protection Against Airborne Contamination Ultrapure Water: Type I...38 Technologies Used to Produce Type I Water...38 Ion-Exchange Resin...38 Synthetic Activated Carbon...38 UV Photooxidation Lamps...38 Microfiltration Membranes...39 Ultrafiltration Membranes...39 Ultrapure Water Systems Milli-Q Integral Water Purification System Direct-Q 3 Water Purification Systems...42 Direct-Q 5 Water Purification Systems...43 Milli-Q Advantage Water Purification System Milli-Q Century Range Water Purification Systems Synergy Water Purification Systems Simplicity Water Purification Systems Super-Q Plus Water Purification System...49 Point-of-Use Purifiers...50 Millipak Filter Units...50 BioPak Polisher EDS-Pak Polisher Service Solutions...52 Preventive Maintenance Plans for Optimal Water Quality...53 Qualification Services for Validation...53 Support and Expertise...54 Technical Support...55 Project Management...55 Design and Engineering...55 Training Support...55 Scientific Support...55 Table of Contents 03

4 Water purification Scientists work in many types of laboratories on all kinds of applications. Not surprisingly, these laboratories are sensitive to contaminants of different natures. Therefore, different grades of reagents and solvents must be selected and utilized. Water is one of the main reagents in many cases, but its importance is often underestimated. visit for the most up-to-date product listing

5 In analytical chemistry, instruments used for inorganic analysis (atomic absorption, optical emission ICP, ICP-Mass Spectrometry, ion chromatography or titrators) can vary significantly from those used for organic analysis (HPLC, GC, and the various mass spectrometry hyphenated techniques). However, several steps are actually common to most analytical methods. In particular, sample preparation remains a significant step in the analytical procedure. This step often requires the use of purified water. The importance and relevance of using high purity water begins at this moment, when the sample can become contaminated due to a number of reasons: poor quality procedures, use of water whose purity level is not high enough, or improper rinsing of containers and filters. The analysis step itself requires high purity water for several reasons. Most methods require running a blank and diluting standards in order to calibrate the instruments before dosing any substances. In liquid chromatography, high purity solvents will optimize column performance and instrument fluidics, resulting in reduced back pressure, increased column lifetime, no artifact peaks, improved resolution and sensitivity and increased separation reproducibility. Rinsing the tubing, the column and the injection valves also requires particulate-free high purity water. The use of high purity water in an analytical laboratory can substantially reduce the time spent on troubleshooting issues due to contamination of the samples and the instruments. Today high purity water is an integral part of the quality programs in most laboratory environments. In the Life Science area, concerns and requirements are different from those of analytical chemistry. While traces of elements may not be an issue, the presence of bacteria by-products, such as pyrogens, or bacteria themselves, can have a significant impact on experiments. In the genomics field, scientists require nuclease-free water in order to prevent sample degradation and maintain integrity of the RNA and DNA collected and studied. While DEPC treatment has long been used, an alternative nuclease-free water production method now exists. Purification of water using ultrafiltration was shown to be fully efficient in producing nuclease-free water, suitable for genomics experiments. More and more scientists around the world are selecting this simple and efficient technique to replace the cumbersome DEPC treatment procedure. In proteomics, it is crucial to prevent degradation or contamination of the protein sample. In order to successfully separate the proteins using 2D-PAGE or nano-lc, the quality of the reagents, including the high purity water, is determinant. The protein or peptide analysis steps that use MALDI-ToF-MS or MS/MS also require extremely pure reagents in order to avoid pollution of the mass spectrometer ionization chambers as well as interferences in the mass analysis. Therefore, in proteomics, high resistivity, low organic content, protease-free and bacteria-free water should be selected and used freshly produced. Water Purification 05

6 WATER CONTAMINANTs Natural water contains five major classes of contaminants that are also present in tap water. Inorganic Ions 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. Organics Dissolved.organic.molecules.present.in.tap.water.are. mainly.of.biological.origin..molecules.including.humic. acids,.tannins,.and.lignin.are.the.by-products.of.the.decay. of.plants..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. 06 WATER PURIFICATION

7 Particulates and Colloids Natural.water.usually.contains.soft.particulates.(vegetal. debris).and.hard.particulates.(sand,.rock).as.well.as. colloids.that.can.interfere.with.instrument.operation. Bacteria and their By-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.pyrogens,.nucleases.or.alkaline. phosphatase. Gases Natural.water.contains.dissolved.gases.such.as.nitrogen,. oxygen.and.carbon.dioxide..the.concentration.of.oxygen. can.affect.specific.biochemical.reactions.and.nitrogen. can.form.bubbles.that.are.detrimental.to.processes. such.as.particulate.counting.or.spectrophotometric. measurements. WATER PURIFICATION 07

8 Monitoring of Water Contaminants Two classes of contaminants, inorganic salts and dissolved organics, are known to affect most laboratory experiments and it is therefore important that they are monitored online in laboratory water systems. Measuring Resistivity to Detect Ions Electrical conductivity is a measure of a material s ability to conduct an electric current. Water itself has a weak electrical conductivity. Electric current is transported in water by dissolved ions, making conductivity measurement a quick and reliable way to monitor the total amount of ionic contaminants in water. c = F.Σ c i z i u i As conductivity also is related to ion mobility (which increases with temperature), conductivity values usually are reported compensated at 25 C, in 25 C. Resistivity, expressed in MΩ. 25 C, is the inverse of conductivity. Traditionally, conductivity is used for values above C, and resistivity for conductivity values below 1 25 C. Temperature measurement performed by a thermistor with 0.1 C sensitivity provides fast and accurate reaction to temperature variations in water. Meters are able to display either resistivity or conductivity readings, compensated or noncompensated at 25 C. The meter s electronic circuit is regularly verified by an automatic process, and alarm messages will be sent if the electric or electronic parts are defective, ensuring that every result displayed is valid. The meters are calibrated with a method developed for use with high resisitivity water, and are delivered with a certificate of calibration. Meters meet requirements for performance of USP 645 suitability tests. These meters provide continuous, reliable insurance that water produced by Elix, Milli-Q and AFS water purification systems will contain low levels of ionic contaminants. Electrodes R = 1/c Water quality of high purity therefore will be expressed as resistivity in MΩ. 25 C. Support Block Water Flow Millipore Resistivity Meters The resistivity meters designed by Millipore for use with ultrapure water take specific needs into consideration: Thermistor Cell design is based on concentric electrodes, in order to generate a large surface and reduce the space between electrodes without risk of contact, therefore achieving the low cell constant (around 0.01 cm -1 ) recommended in ASTM D Electrodes made of 316 L stainless steel are used to minimize corrosion and ion release risks. Flow-through cell design allows immediate detection of any ionic contamination in the water flow. Milli-Q System High Precision Coaxial Resistivity Cell The conductivity measurement is performed by dipping two electrodes in an aqueous solution. An electrical potential (below 1.23 V) is established between the two electrodes and the intensity of current passing through the circuit is measured. The conductivity of the solution will be proportional to the electrical current. 08 Water Purification

9 Measuring TOC to Detect Organics TOC means Total Oxidizable Carbon and is sometimes referred as Total Organic Carbon. Water may contain hundreds of different organic substances at different levels of oxidation, and at different concentrations. TOC expresses the organic contamination of water with a single figure. Millipore TOC Monitors The Millipore A10 TOC monitor contains a 0.5 ml quartz cell in which ultrapure water is captured. When the A10 UV lamp is powered on, photocatalytic oxidation of the organic compounds occurs. The final end product of the organic oxidation is carbon dioxide, which dissolves in the water, causing a conductivity increase. This change in conductivity is regularly monitored by the titanium electrodes (patented design) and temperaturecompensated to 25 C. A set of complex algorithms confirms complete oxidation and calculates the carbon level associated with this conductivity change. Millipore TOC monitors are available as stand alone units or integrated within some Milli-Q and Elix water purification systems. The TOC monitor design offers several benefits: As the oxidation and conductivity measurement occurs in the same cell, the instrument checks that all organics have been oxidized, and that a stable conductivity value has been reached before delivering a TOC value. Otherwise, the A10 monitor will indicate that it did not succeed in oxidizing all organics and will start a new test. The A10 TOC monitor is able to detect TOC values over a range of 1 to 999 ppb TOC, with an accuracy of ± 1 ppb or 15 %, whichever is greatest. Each A10 TOC monitor is calibrated for resistivity around two values: 18.0 MΩ. 25 C and 1 MΩ. 25 C, and for TOC with methanol over a range between 1 and 200 ppb TOC. The calibration results of each TOC monitor are delivered with the instrument. Millipore A10 TOC monitors meet the requirements for the performance of suitability tests as described in USP 643. These tests can be performed with the support of Millipore Service Engineers. Millipore A10 TOC monitors provide an accurate measure of the TOC value in the ultrapure water produced and therefore a warranty of the quality of that water. Conductivity Fill Valve.open Lamp.on Solenoid Valve Thermistor Measure.of.initial conductivity. &.temperature Lamp.off Titanium Electrodes Quartz.cell 0.5.ml Oxidation cycle Valve.closed Lamp.on A10 TOC Monitor Photooxidation Cycle 185/254.nm UV.Lamp A10 TOC Monitor Photooxidation Cell The A10 TOC monitor contains a quartz cell. Water flows through a channel at the base of the cell and then exits through a solenoid valve at the top. Titanium electrodes in the cell allow conductivity to be measured; a thermistor on the side measures temperature. A 185 /254 nm UV lamp located next to the cell can emit UV light. Purge Valve.open Time Water Purification 09

10 Laboratory Water Types Norms define different laboratory water grades for both technical and economical reasons. The purpose of these norms is to ensure that the right water quality is used for a specific application, while limiting laboratory operating costs Type I water is more expensive to produce than Type II or Type III water. Type III Type III water is the lowest laboratory water grade, recommended for glassware rinsing, heating baths and filling autoclaves, or to feed Type I lab water systems. Type II Type II water is the grade used in general laboratory applications such as buffers, ph solutions and microbiological culture media preparation; as feed to. Type I water systems, clinical analyzers, cell culture incubators and weatherometers; and for preparation of reagents for chemical analysis or synthesis. Type I Type I water is the grade required for critical laboratory applications such as HPLC mobile phase preparation, blanks and sample dilution in GC, HPLC, AA, ICP-MS and other advanced analytical techniques; preparation of buffers and culture media for mammalian cell culture and IVF; production of reagents for molecular biology applications (DNA sequencing, PCR); and preparation of solutions for electrophoresis and blotting. Using Type I water for Type II. water applications is a common laboratory practice in order to decrease the risk of artifact generation during experimental procedures. Laboratory Water Specifications Different published norms define the quality required for specific laboratory water applications: ASTM and ISO 3696 for laboratory applications; CLSI guidelines for clinical laboratories. Some laboratories will also use norms defined in the European or the US Pharmacopoeia. The table below outlines the different water specifications based on the different water types. Contaminant Parameter and unit Type III Type II Type I Ions Resistivity (MΩ.cm) > 0.05 > 1.0 > 18.0 Organics TOC (ppb) < 200 < 50 < 10 Pyrogens (EU / ml) NA NA < 0.03 Particulates Particulates > 0.2 µm (units / ml) NA NA < 1 Colloids Silica (ppb) < 1000 < 100 < 10 Bacteria Bacteria (cfu / ml) < 1000 < 100 < 1 These values are only guidelines, as some specific laboratory applications may require a quality superior to the quality indicated by the norms. For instance, several molecular biology applications require Type I water that is both RNase-free and DNase-free; elemental trace analysis at sub ppt levels requires water of a higher purity than regular Type I water; and glassware washing may require pyrogen-free water for some experiments. Millipore has done extensive research into laboratory water applications. This information, compiled as internal research notes or references to scientific articles, is provided on demand by our Application Specialists. (Visit / offices to find your nearest contact). 10 Water Purification

11 Overview of Purification Technologies The major water purification technologies are described below. Each technology has its benefits and limitations. Some are able to remove a large fraction of several contaminants, while others excel at removing one specific type of impurity down to very low levels. As a result, in order to remove all contaminants to the levels required for critical applications, it is necessary to use a combination of technologies. Distillation Distillation is probably the oldest method of water purification. Water is first heated to the boiling point. The water vapor rises to a condenser where cooling water lowers the temperature so the vapor is condensed, collected and stored. Cooling.Device may be generated during the distillation process, which provides the energy required for chlorine in the tap water (added for sanitization purposes) to react with the natural organic substances also present in this water. This explains why the TOC level of distilled water is typically around 100 ppb. Distillation is a slow process that requires storage of water for long periods. During this time, recontamination occurs from the ambient air (inorganic and organic volatile substances, bacteria, particulates and algae) and the container (organics from plastic tanks or ions from glass reservoirs). Distillation requires large amounts of energy and water, and therefore is expensive to operate. In addition, a still requires regular cleaning of the boiling pot with HCl, a brush and sand paper to remove the contaminants accumulated during the process. Heat Storage Distillation Benefits..Removes a broad range of contaminants and therefore useful as a first purification step...reusable. Many contaminants remain behind in the boiling vessel. However, the process has several limitations: Inorganic contaminants are able to migrate along the thin water film that forms on the inner walls of the still. This explains why ions can be found in the distillate, whose resistivity is therefore usually between 0.5 and 1 MΩ. 25 C (i.e., about 500 ppb total ionic contamination in water). Contaminants are also extracted from the glass or metal boiling pot used to heat the water (silica, sodium, tin, copper). Organics with boiling points lower than 100 C will automatically be transferred to the distillate, and even organics with a boiling point superior to 100 C can dissolve in the water vapor and also pass into the distillate. In addition, new organochlorine compounds Limitations..Contaminants are carried to some extent into the condensate...requires careful maintenance to ensure purity...consumes large amounts of tap water (for cooling) and electrical energy (for heating)...not environmental friendly. Water Purification 11

12 Ion Exchange The ion-exchange process percolates water through spherical, porous bead resin materials (ion-exchange resins). Ions in the water are exchanged for other ions fixed to the beads. The two most common ion-exchange methods are softening and deionization. Softening is used primarily as a pretreatment method to reduce water hardness prior to reverse osmosis (RO) processing. The softeners contain beads that exchange two sodium ions for every calcium or magnesium ion removed from softened water. Jetpore ion-exchange resin beads NaCI OH - H OH - H H OH - Cl - Na Cl - Na Na Cl - H OH - H 2 O The resin may be regenerated by strong acid and bases once it has exchanged all its hydrogen and / or hydroxyl ions for charged contaminants in the water. This regeneration reverses the purification process, replacing the contaminants bound to the DI resins with hydrogen and hydroxyl ions. However, this is a harsh chemical process that may damage the polymer chains constituting the beads, leading to contamination of the resin by organics and particulates, and creating an issue in the production of high purity water. Deionization Deionization (DI) beads exchange either hydrogen ions for cations, or hydroxyl ions for anions. The cationexchange resins, which are made of polystyrene chains cross-linked by divinylbenzene with covalently bound sulfonic acid groups, will exchange a hydrogen ion for any cations they encounter (e.g., Na +, Ca ++, Al +++ ). Similarly, the anion-exchange resins, which are made of polystyrene polymer chains with covalently bound quaternary ammonium groups, will exchange a hydroxyl for any anions (e.g., Cl -, NO3 -, SO4 -- ). The hydrogen ion from the cation exchanger unites with the hydroxyl ion of the anion exchanger to form pure water. These resins may be packaged in separate bed exchangers with separate units for the cation and anion exchange beds. Or, they may be packaged in mixed bed exchangers containing a mixture of both types of resins. This last configuration enables more efficient ion removal and provides higher water resistivity values. For the production of high purity water, two solutions exist:..use virgin mixed bed ion-exchange resin packs containing monosphere beads with low TOC (such as Millipore Jetpore ion-exchange resin) only once and discard the pack after usage. This is an economically acceptable process provided that these packs are fed by pretreated water of good quality to limit the replacement frequency. A good pretreatment should remove not only the bulk of ions to limit the burden of ionic contaminants reaching the resin pack, but also organics, particulates and colloids. This is required to prevent the build-up on the resin beads of a coating preventing the ions from accessing the ionic binding sites located mainly inside the beads porous structure...perform the regeneration of the ion-exchange resins using a gentle and continuous procedure such as electrodeionization, in order to avoid damaging the. ion-exchange resin beads and consequently generating contaminants. This process was developed by Millipore in the 1980s. 12 Water Purification

13 Deionization can be an important component of a total water purification system when used in combination with other methods such as RO, filtration and carbon adsorption. DI systems effectively remove ions, but they do not effectively remove most organics and microorganisms. Microorganisms can attach to the resins, providing a culture media for bacteria growth and subsequent pyrogen generation over the long run. The benefits and limitations of this technology are summarized below. Benefits..Removes dissolved inorganics (ions) effectively, allowing resistivity levels above C. to be reached (corresponding roughly to less than 1 ppb total ionic contamination in water)...regenerable (by acid and bases in service deionization or by electrodeionization)...relatively inexpensive initial capital investment. Limitations..Limited capacity: once all ion binding sites are occupied, ions are no longer retained (except when operating in an electodeionization process)...does not effectively remove organics, particles, pyrogens or bacteria...chemically regenerated DI beds can generate organics and particles...single use, virgin resins require good pretreated water quality to be economically efficient. Water Purification 13

14 Activated Carbon Activated carbon is made of organic material porous particulates containing a maze of small pores, which account for the substance s highly developed surface. One gram of activated carbon has a surface of up to m 2. Organic molecules dissolved in water may enter the pores and bind to their walls due to van der Waals forces. The adsorption process is controlled by the diameter of the pores in the carbon filter and by the diffusion rate of organic molecules through the pores. The rate of adsorption is a function of molecular weight and the molecular size of the organics. Flow Activated carbon used in water purification is available in two forms: Natural activated carbon produced by treating vegetal products such as coconut shells at high temperature. The result of this process is a fine powder made of irregularly shaped grains. Natural activated carbon contains a high concentration of ionic contaminants and is therefore used only as a pretreatment step to remove excess chlorine from tap water by a reduction reaction and, to some extent, to reduce organic contamination. synthetic activated carbon is made by the controlled pyrolysis of polystyrene spherical beads. This cleaner material is used for the removal of trace organics of low molecular weight. Bacteria Dissolved.Organics Dissolved.Inorganics Particles Carbon Adsorption Activated carbon is usually 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. Synthetic activated carbon Benefits..Removes dissolved organics and chlorine effectively...long life due to high binding capacity. Limitations..Does not efficiently remove ions and particulates...limited capacity due to a high, but limited, number of binding sites...can generate carbon fines. 14 Water Purification

15 Microporous Filters Microporous filters can be classified in three categories: depth, surface and screen. Depth filters are matted fibers or materials compressed to form a matrix that retains particles by random adsorption or entrapment. Surface filters are made from multiple layers of media. When fluid passes through the filter, particles larger than the spaces within the filter matrix are retained, accumulating primarily on the surface of the filter.. Screen filters (also called membrane filters) are inherently uniform structures which, like a sieve, retain all particles larger than the precisely controlled pore size on their surface. The distinction between filters is important because the three serve very different functions. Depth filters are usually used as prefilters because they are an economical way to remove 98 % of suspended solids and protect elements downstream from fouling or clogging. They owe their high capacity to the fact that contaminants are trapped and retained within the whole filter depth. Surface filters remove % of suspended solids and may be used either as prefilters or clarifying filters. Screen (microporous membrane) filters are 100 % efficient at retaining contaminants larger than their pore size. These filters are placed at the furthest possible point in a system to remove the last remaining traces of resin fragments, carbon fines, colloidal particles and microorganisms. For example, 0.22 μm Millipore membrane filters, which retain all bacteria, are routinely used to sterilize intravenous solutions, serums and antibiotics. Depth Filter Benefits..Screen filters are absolute filters that remove all particles and microorganisms greater than their pore size...efficient operation throughout their lifetime, unless they are damaged...maintenance is limited to replacement. Screen Filter Limitations..They will clog when the surface is covered by contaminants. Therefore, they should be used as a last purification step, as a type of insurance...will not remove dissolved inorganics, organics or pyrogens...not regenerable. Water Purification 15

16 Ultrafiltration A microporous membrane filter removes particles according to pore size. By contrast, an ultrafiltration (UF) membrane functions as a molecular sieve. It separates dissolved molecules on the basis of their size often reported as the molecular weight (both parameters are related, but not always directly) by passing a solution through an infinitesimally fine filter. The ultrafilter is a tough, thin, selectively permeable membrane that retains most macromolecules above a certain size (Nominal Molecular Weight Limit, or NMWL) including colloids, microorganisms and pyrogens. Smaller molecules, such as solvents and ionized contaminants, are allowed to pass into the filtrate. Thus, UF provides a retained fraction (retentate) that is rich in large molecules and a filtrate that contains few, if any, of these molecules. Benefits..Effectively removes most particles, pyrogens, enzymes, microorganisms and colloids above their rated size, retaining them above the ultrafilter surface...efficient operation throughout their lifetime, unless they are damaged...their lifetime can be extended by a regular water flush at high speed. Limitations..Will not remove dissolved inorganics or organic substances...may clog when challenged by an excessive level of high-molecular-weight contaminants. Ultrafilter Ultrafilters are available in several selective ranges. In all cases, the membranes will retain most, but not necessarily all, molecules above their rated size. In water purification, ultrafilters are routinely used to provide pyrogen-free and nuclease-free water for critical cell culture or molecular biology experimentation. The key point here is the validation process, which ensures that the ultrafilter, when challenged by pyrogens, RNases or DNases at levels far above those likely to occur during regular operation, will be able to reliably deliver water within specification. 16 Water Purification

17 Reverse Osmosis Reverse osmosis (RO) is the most economical method of removing 95 % to 99 % of all contaminants. The pore structure of RO membranes is much tighter than that of UF membranes. RO membranes are capable of rejecting practically all particles, bacteria and organics > 200 Dalton molecular weight (including pyrogens) at a rate close to 99 %. Natural osmosis occurs when solutions with two different concentrations are separated by a semi-permeable membrane. Osmotic pressure drives water through the membrane; the water dilutes the more concentrated solution; and the end result is an equilibrium. In water purification systems, hydraulic pressure is applied to the concentrated solution to counteract the osmotic pressure. Pure water is driven from the concentrated solution at a flow rate proportional to applied pressure and collected downstream of the membrane. Because RO membranes are very restrictive, they yield slow flow rates per surface unit. Storage tanks are required to produce an adequate volume in a reasonable amount of time. Therefore, the membrane rejects nearly all (> 99 %) strongly ionized polyvalent ions but only more than 95 % of the monovalent ions like sodium. Salt rejection increases significantly with applied pressure up to 5 bar. Different feed water may require different types of RO membranes. Membranes are manufactured from cellulose acetate or thin-film composites of polyamide on a polysulfone substrate. If the system is properly designed for the feed water conditions and the intended use of the product water, RO is the most economical and efficient method for purifying tap water. RO is also the optimum pretreatment for reagent-grade water polishing systems. Benefits..Effectively removes all types of contaminants to some extent (particles, 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. Limitations..Limited flow rates per surface unit require either large membrane surfaces or an intermediate storage device to satisfy user demand...requires good pretreatment to avoid rapid membrane damage by water contaminants: scaling (CaCO 3 deposits on the surface), fouling (deposits of organics or colloids on the surface) or piercing (RO membrane cut by hard particulates). Reverse Osmosis RO also involves an ionic exclusion process. Only solvent (i.e., water molecules) is allowed to pass through the semi-permeable RO membrane, while virtually all ions and dissolved molecules are retained (including salts and organic molecules such as sugars). The semi-permeable membrane rejects salts (ions) by a charge phenomenon action: the greater the charge, the greater the rejection. Water Purification 17

18 Elix Continuous Deionization This technology is a combination of electrodialysis and ion exchange, resulting in a process which 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 systems. 1 Anode Feedwater Electrode Channel H + Na + Cl - Cl - H + Cl - Purifying Channel Concentrating Channel 4 Na + Cl - The Elix module consists of a number of cells sandwiched between two electrodes. Each cell consists of a polypropylene frame onto which are bonded a cationpermeable membrane on one side, and an anion-permeable membrane on the other. The space in the center of the cell, between the ionselective membranes, is filled with a thin bed of ionexchange resins. The cells are separated from one another by a screen separator. The feed water entering the module is split into three parts. A small percentage flows over the electrodes, % of the feed passes through the resin beds in the cell, and the remainder passes along the screen separator between the cells. The ion-exchange resins capture dissolved ions in the feed water at the top of the cell. Electric current applied across the module pulls those ions through the ionselective 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 Purifying Channel Electrode channel OH - Na + OH - Na + 6 Waste 7 Product Anion.Permeable.Membrane Cation.Permeable.Membrane Elix.technology.purification.steps 5 Cathode 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. At the lower end of the dilute channel, where water is free of ions, splitting of H 2 O occurs in the electric field. This generates H + and OH - which regenerate the ion-exchange resins, effectively eliminating chemical regeneration. Benefits..Removes dissolved inorganics effectively, allowing resistivity above 5 25 C to be reached (which corresponds to a total ionic contamination level in water of approximately. 50 ppb)...environmental friendly:. - No chemical regeneration.. - No chemical disposal.. - No resin disposal...inexpensive to operate...safe: no heating element. Limitations..Removes only a limited number of charged organics...requires feed by good quality water (for instance, reverse osmosis-treated water) for economically efficient operation. 18 Water Purification

19 Ultraviolet (UV) Radiation Ultraviolet radiation has been widely used as a germicidal treatment for water. Mercury low pressure UV lamps generate light at different wavelengths, including 185 and 254 nm. UV lamps with a regular quartz sleeve allow passage of 254 nm light. These lamps are an effective means of sanitizing water. The adsorption of UV light by the DNA in the microbial cells results in the inactivation of the microorganism. UV lamps with a very pure quartz sleeve allow passage of both 185 and 254 nm UV light. This combination of wavelengths is necessary for the photooxidation of organic compounds, which ultimately allows conversion of dissolved organic substances into carbon dioxide. With these special lamps, Total Oxidizable Carbon (TOC) levels in high purity water can be reduced to 5 ppb. Relative Effectiveness 100% 80.% 60% 254.nm 40% 20% 0% Wavelength (nm) Benefits..Effective sanitizing treatment...oxidation of organic compounds (185 nm and 254 nm) to reach water TOC levels below 5 ppb. Limitations..Photooxidation of organics is a polishing step, able to decrease the TOC level only by a limited value...the CO 2 produced during photooxidation decreases the water s resistivity, as it reacts with water to produce H 2 Co 3, splitting into HCO 3 - and H +...UV light will not affect ions, particles or colloids. Water Purification 19

20 WATER PURIFICATION systems ADAPTED TO specific NEEDs Millipore s range of water purification systems is designed to provide laboratories with systems covering the three different water types in an efficient and economical way that includes adapted monitoring and quality assurance. The graph below shows a summary of the systems available and can help you select the system best suited to your application needs. However, each laboratory has its own constraints and our application specialists are available to answer your questions and support you in the design of the system that best matches your needs. Visit www. millipore.com / offices to find your nearest contact. Water Quality Type I Type II Type III Ta p systems 3 systems systems systems 3/5 systems systems 3/5/10/15 systems systems Century Advantage systems 3/5/10/15 Integral systems 20/35/70/100 systems 30/50/100/150/200 systems Volume in liters/day * Advanced Technical support A.complete.range.of.services,.including.validation.support,.is.provided.by.trained.Millipore.Field. Service.Support.Engineers.using.calibrated.equipment.and.Qualifi. cation.workbooks

21 System Water Source Final Water Quality Application RiOs.3 Tap Type.III Production.of.up.to.30.l.of.pure.water.per.day.to.feed.autoclaves.or. glassware.washing.machines.and./.or.feed.water.for.milli-q.systems. RiOs * Tap Type.III Production.of.pure.water.for.laboratories.using.up.to.350.l.per.day. RiOs * Tap Type.III Production.of.pure.water.for.daily.needs.up.to l.per.day.. Elix * Tap Type.II Production.of.pure.water.for.laboratories.needing.up.to.200.l.per. day.of.water.superior.in.quality.to.double.distilled.water. Elix * Tap Type.II Production.of.pure.water.for.daily.needs.up.to l.per.day..RiOs-DI.3 Tap Type.II Milli-DI Tap Type.II An.economical.alternative.to.stills.for.labs.requiring.up.to.15.l.of. purified.water.per.day. Low.capital.investment.system.for.labs.that.require.up.to.10.l.per. day.of.di.water.for.non-critical.applications. Elix.Clinical * Tap NA ** Feed.for.clinical.analyzers.needing.up.to l.per.day. AFS * Tap NA ** Feed.for.clinical.analyzers.needing.up.to.350.l.per.day. Milli-Q.Integral * Tap Type.I,.Type.II Milli-Q.Advantage * Type.III.or.II Type.I Milli-Q.Century * Type.III.or.II Type.I Direct-Q.5 * Tap Type.I,.Type.III.Direct-Q.3 Tap Type.I,.Type.III Production.of.pure.water.for.laboratories.needing.up.to.350.l per.day.of.water.superior.in.quality.to.double.distilled.water.. Ultrapure.water.designed.for.pharmaceutical.and.biotech.research. applications.and.qc.labs.needing.from.1.to.350.l.per.day. Ultrapure.water.designed.for.pharmaceutical.and.biotech.research. applications.and.qc.labs.needing.from.1.to.200.l.per.day. Ultrapure.water.systems.tailored.for.specific.applications.in. research.and.qc.labs.needing.1.to.200.l.per.day. Designed.for.labs.using.1.to.15.l.of.ultrapure.water.per.day.and.up.to. 100.l.of.Type.III.water.per.day. Designed.for.labs.using.1.to.10.l.of.ultrapure.water.per.day.and.up.to. 50.l.of.Type.III.water.per.day. Synergy Type.III.or.II Type.I Designed.for.labs.using.1.to.40.l.ultrapure.water.per.day. Simplicity Type.III.or.II Type.I Designed.for.labs.using.1.to.5.l.ultrapure.water.per.day..An. economical.alternative.to.bottled.water. Super-Q Type.III.or.II Type.I Production.of.ultrapure.water.with.high.instant.flow.rate.(12.l/min). *..Advanced.Technical.Support A.complete.range.of.services,.including.validation.support,.is. provided.by.trained.millipore.field.service.engineers.using. calibrated.equipment.and.qualifi. cation.workbooks. **.Designed.to.be.in.compliance.with.CLSI.CLRW.quantitative. specifi. cations...millipore lab water systems can be combined to achieve specific laboratory objectives. For instance, an Elix system combined with a reservoir and a Milli-Q Advantage system will fulfill the following requirements in a laboratory:...production.of.type.ii.water.for.non-critical.applications. such.as.buffer.and.reagent.preparation...production.of.type.i.ultrapure.water.for.critical. laboratory.applications WATER PURIFICATION systems ADAPTED TO specific NEEDs 21

22 Type III Water Technologies used to produce Type III water Various purification technologies exist, each with its own benefits and limitations. To remove all contaminants to the levels required for specific applications, it is necessary to use a combination of technologies. Reverse Osmosis (RO) is the most economical method for removing 90 % to 99 % of all contaminants and Millipore Type III systems combine different steps as outlined in the graph below to optimize the RO process. Tap Step 1 Progard Pack Protection of RO against scaling (CaCO 3 ), piercing (particulates) and oxidation by chlorine Step 2 Reverse Osmosis Removal of up to 99 % of feed water contaminants Step 3 UV Lamp 254 nm Production of water with low levels of bacteria 22 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

23 Pretreatment to protect the RO membrane The high quality Progard pretreatment pack minimizes the risk of clogging the RO membrane and guarantees the lifetime of the equipment...the pretreatment pack contains (1) carbon beads, (2) anti-scaling compounds and (3) a prefilter to efficiently protect the RO membrane(s) against plugging, scaling and oxidation...silver-impregnated carbon cartridges (optional cartridge version S1 or S2) are adapted to areas where the feed water has high bacterial levels...the Progard packs come in two different sizes to cover a range of feed water conditions Progard Pretreatment Pack Reverse Osmosis to purify Type III water is produced by the latest Reverse Osmosis (RO) technology. This method is capable of rejecting up to 99 % of the contaminants present in potable water by passing pressurized feed water through a polyamide membrane. The different types of contaminants are efficiently removed. Laboratory-grade water is frequently used in laboratories mainly for applications such as:..glassware rinsing..feed water for humidifiers, autoclaves, washing machines..feed water for Milli-Q ultrapure water systems Reverse Osmosis WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 23

24 Type III Water Purification Systems RiOs 3 Water Purification Systems Economical pure water solution for low volume needs Produce up to l / day of Pure Water (Type III Water) from Tap. Because optimum quality water requires appropriate flow rate sizing, Millipore has especially developed a 3 l / hour system for small volume needs. Water is conveniently stored inside the unit to save space. Features..Unique all-in-one consumable pack includes pretreatment and reverse osmosis membrane...maintenance reduced to changing a single cartridge once or twice a year...backlit color display shows conductivity, temperature and water level in reservoir...integrated, compact 6-liter reservoir; (connection to a 30 l or 60 l reservoir possible for higher daily needs)...efficient removal > 94 % of ionic contaminants...efficient removal > 99 % of other contaminants (organics, bacteria, particles). RiOs 5 / 8 / 16 Water Purification Systems The advanced RO system for laboratories Produce up to 350 l / day of Pure Water (Type III) from Tap. Features..Easy to maintain...self-maintenance functions of the reverse osmosis membrane...advanced reverse osmosis technology with high recovery loop reduces water consumption by more than 50 %...Constant product flow rate...optional UV lamp for optimum water quality for applications sensitive to bacteria...all system functions accessible from a user-friendly keypad and displayed on backlit screen. Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation and rinsing of glassware. In addition, it may be used in water baths. It may also be used as the pretreatment step for an ultrapure water purification system. 24 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

25 RiOs 30 / 50 / 100 / 150 / 200 Water Purification Systems One complete purification and control unit for large labs or a whole laboratory building Produce up to 4000 l / day of Pure Water (Type III). Features..Total control of all functions, operating parameters and standard accessory components within the RiOs system itself and in the pure water distribution loop...high water recovery thanks to advanced reverse osmosis technology...constant product flow rate independent of temperature from 7 30 C...Built-in UV lamp for bacteria-sensitive applications...easy-to-replace pretreatment packs, tailored to the feed water source...built-in conductivity monitoring to ensure water quality. Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation and rinsing of glassware. In addition, it may be used in water baths, autoclaves, to feed laboratory dishwashers and as a water source for animal facilities and aquariums. It may also be used as the pretreatment step for an ultrapure water system. Specifications RiOs 5 RiOs 8 RiOs 16 RiOs 30 RiOs 50 RiOs 100 RiOs 150 RiOs 200 Flow Rate, l / h + / - 15 %. at 7 C < T< 30 C) Water Recovery, % up to 45 up to 50 up to 70 up to 70 up to 70 Ion Rejection, % Organic Rejection, %. (MW > 200 Dalton) Particle Rejection, % Bacteria, cfu / ml < 1* < 1* < 1* < 10 < 10 < 10 < 10 < 10 * Valid for systems with UV lamp Ordering Information Visit / catalogue or find your local office telephone number by visiting and Millipore specialists will guide you through the best choice for your application needs. WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 25

26 Type II Water Technologies Used to Produce Type II Water There are various purification technologies that can produce Type II water. The most efficient way of producing Type II water is to begin with Reverse Osmosis and follow with either deionization (RO-DI) or Electrodeionization (RO-EDI). Millipore systems combine these technologies in a comprehensive range of systems. Tap Step 1 Progard Pack Protection of RO against scaling (CaCO 3 ), piercing (particulates) and oxidation by chlorine Step 2 Reverse Osmosis Removal of up to 99 % of feed water contaminants Step 3 1 Anode Feedwater C Electrode Channel H + Na + Cl - H + Cl - A Purifying Concentrating Purifying Channel Channel Channel C Cl - 4 Cl - Na + 6 Waste 7 A C Anion.Permeable.Membrane Cation.Permeable.Membrane Elix.technology.purification.steps A C Electrode channel 5 OH - Na + OH - Na + Product - Cathode Elix Module or DI Consistent production of high resistivity and low TOC water Step 4 UV Lamp * 254 nm Production of water with low levels of bacteria. *optional 26 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

27 Elix Technology..Water entering the Elix module is RO purified Type III water...ion-exchange resins in the module are continuously regenerated via an electrical current. This process requires only very small quantities of water and energy...no special maintenance or chemical regeneration is needed that would deteriorate the resin beads...this unique process has become the new standard for the production of Type II water and is replacing both distillation and conventional deionization units in the laboratory. Features In general, water that has been purified using Elix technology is suitable for use with analyses at the parts per million (ppm) or high ppb levels, and also may be used to fulfill several other needs in a laboratory:..buffer and media preparation, in particular for microbiology, titration (unless trace levels are targeted), ph or general analytical chemistry...non-sensitive sample preparation requiring extensive washing...chemical reactions run in water...stability testing chambers and autoclave feeding...histology...glassware washing; can be used for manual washing or Elix systems can be fitted to dishwashers to deliver water on demand...with additional basic ion-exchange polishing, the water can be used in clinical chemistry and as feed water for weatherometers. Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. In addition, it may be used in water baths, weatherometers, laboratory dishwashers and autoclaves. It may also be used as the pretreatment step for an ultrapure water system. WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 27

28 Type II Water Purification Systems Elix 3 / 5 / 10 Water Purification Systems The standard for pure water in laboratories an efficient, economical alternative to distillation and deionization Produce up to 200 l / day of Type II Water from Tap. Elix system water meets or exceeds Type II water quality as defined by ISO 3696 / BS 3997 and purified water defined by the European and U.S. Pharmacopoeia. With Elix systems, control of water purity is built into every step of the purification process ensuring that water quality will be a constant in your applications, not an additional variable. Features..Easy to maintain and operate. - A unique and easy-to-install prefiltration pack unit. - Self-maintenance of the reverse osmosis membrane..self-regeneration of the ion-exchange resins by an electrical current. - Production of consistent high water quality. - Optimized cost per liter..advanced reverse osmosis technology. - High recovery loop reduces water consumption by...more than 50 %. - Constant product flow rate..integrated UV lamp for optimum water quality for applications sensitive to bacteria..data storage and RS 232 communication port Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. In addition, it may be used in water baths, weatherometers, laboratory dishwashers and autoclaves. It may also be used as the pretreatment step for an ultrapure water system. Specifications Water Needs. per day Flow Rate, l / h + / 15 % at 7 C < T< 30 C) Resistivity. (MΩ.cm) compensated to 25 C)* Conductivity. µs / cm (compensated to 25 C)* Elix 3 Elix 5 Elix 10 Up to 60 l Up to 100 l Up to 200 l > 5 > 5 > 5 < 0.2 < 0.2 < 0.2 TOC, ppb < 30 < 30 < 30 Bacteria Count** cfu / ml < 1 < 1 < 1 Silicate Removal, % > 99.9 > 99.9 > 99.9 Ordering Information Visit or find your local office telephone number by visiting and Millipore specialists will guide you through the best choice for your application needs. Water Recovery, % *..(CO 2 ) 30 ppm in feed water: typical resistivity MΩ.cm. (CO 2 > 30 ppm in feed water; typical resistivity > 2 MΩ.cm) ** Valid for Elix systems with UV lamp 28 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

29 Elix 20 / 35 / 70 / 100 Water Purification Systems One complete purification and control unit Produce up to 2000 l / day of Type II Water. Elix 20 / 35 / 70 / 100 systems are designed to produce up to l / day of Type II water from potable tap feed water to meet or exceed the relevant standards defined by CLSI, ISO 3696 / BS 3997 and the European and US Pharmacopoeia.Elix systems can be integrated into a centralized system, providing total control of all parameters. Features..Total control of all functions, operating parameters and standard accessory components within the Elix system itself and within the external pure water distribution loop..patented Elix electrodeionization (EDI) module continuously regenerates ion-exchange resins..built-in resistivity and TOC (Total Oxidizable Carbon) monitoring ensures water quality..no additional softeners are required for most feed water conditions..easy-to-replace pretreatment packs, tailored to the feed water source..built-in UV lamp for bacteria-sensitive applications Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation and rinsing of glassware. In addition, it may be used in water baths, weatherometers, laboratory dishwashers and autoclaves. It is recommended for use in chemical and pharmaceutical QA/QC laboratories, and in central water distribution systems. It may also be used as the pretreatment step for an ultrapure water system. Specifications Water Needs. per day Flow Rate, l / h + / 15 % at 7 C < T< 30 C) Resistivity. (MΩ.cm) compensated to 25 C)* Conductivity. µs / cm (compensated to 25 C)* Elix 20 Elix 35 Elix 70 Elix 100 Up to 400 l Up to 700 l Up to 1400 l Up to2000 l > 5 > 5 > 5 > 5 < 0.2 < 0.2 < 0.2 < 0.2 TOC, ppb < 30 < 30 < 30 < 30 Bacteria Count** cfu / ml < 10 < 10 < 10 < 10 Silicate Removal, % > 99.9 > 99.9 > 99.9 > 99.9 Water Recovery, % Up to 30 Up to 40 Up to 50 Up to 50 *..(CO 2 ) 30 ppm in feed water: typical resistivity MΩ.cm. (CO 2 > 30 ppm in feed water; typical resistivity > 2 MΩ.cm) ** Valid for Elix systems with UV lamp WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 29

30 Systems for Low Volume Daily Needs RiOs-DI 3 Water Purification Systems For low volumes (< 10 l / day) of pure water (Type II) from tap The RiOs-DI 3 UV system is a very compact solution that efficiently combines reverse osmosis (RO) technology with deionization (DI) resins to produce high quality pure water of high resistivity and low TOC (> 10 MΩ.cm at 25 C and < 50 ppb). The system s product water is stored in an internal reservoir and is ideal for low volume routine laboratory applications. Features..Maintenance is reduced to the quick change of a single cartridge...the consumable is a unique all-in-one pack that includes the pretreatment, reverse osmosis membrane and ion-exchange resin...integrated, compact 6-liter reservoir...the built-in UV lamp* is ideal for applications that require low bacteria levels...backlit color display shows resistivity, temperature and water level in reservoir. * This system is also available without UV lamp. Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation and rinsing of glassware. In addition, it may be used in water baths. It may also be used as the pretreatment step for an ultrapure water purification system. Specifications Resistivity, MΩ.cm at 25 C Typically >10 Average Daily Needs 5 to 10 L per day Flow Rate, l/h >2.4 l/h at 15 C Organics, ppb <50 30 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

31 Milli-DI Water Purification Systems Produce deionized water directly from tap water The.Milli-DI.system.is.a.compact.and.easy-to-use.water. purification.system.that.instantly.provides.deionized. water.(resistivity.>.1.mω.cm.at.25. C).directly.from.tap. water..suitable.for.users.requiring.low.volumes.of.purified. water,.3.to.5.l./.day,.this.battery-powered.system.comes. with.everything.needed.for.easy.installation.in.the.lab. (includes.tubing.for.½.tap.fitting). Features...Low.investment....Cartridge.contains.high.quality.mixed-bed.resins....Optional.0.22.µm.filter.produces.bacteria-free.water....A.green.LED.light.indicates.good.water.quality,.and.a.red. LED.light.indicates.that.the.DI-PAK.purification.pack. needs.to.be.replaced. Applications The.water.produced.by.these.systems.may.be. used.for.basic.laboratory.needs,.such.as.buffer. and.reagent.preparation,.microbiology.media. preparation.and.rinsing.of.glassware..in.addition,. it.may.be.used.in.water.baths..it.may.also.be.used. as.the.pretreatment.step.for.an.ultrapure.water. purification.system. specifications Resistivity,.MΩ.cm.at.25. C >1 Flow.Rate,.l./.min Feed.water.Requirements Potable.tap.water.at.a. feed-pressure.of bar.(14 70.psi) WATER PURIFICATION systems ADAPTED TO specific NEEDs 31

32 Solutions for Clinical Analyzers Millipore offers a complete range of water purification systems designed to match the needs of small through large volume applications. Compatible with any analyzer, these systems are economical, easy to use, save water and improve productivity and results. RiOs-DI Clinical Water Purification Systems For low volumes (< 10 l / day) of pure water (Type II) from tap The RiOs-DI Clinical system is a very compact solution designed for low volume analyzers. The system efficiently combines reverse osmosis (RO) technology with deionization (DI) resins to produce CLSI Special Reagent Water*...Produces water with flow rate of 3 l/h..specifically designed to feed low-volume analyzers using up to 20 l/day..designed to be in compliance with CLSI CLRW** quantitative specifications..economical system allows substantial cost savings..provides an efficient alternative to buying and storing bottled water * Clinical and Laboratory Standards Institute (CLSI) SRW type ** Clinical and Laboratory Standards Institute Clinical Laboratory Reagent Water Features..Easy to install..easy to maintain..saves space..advanced water quality monitoring..quiet operation..consumable cartridges snap in and snap out without tools Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. 32 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

33 AFS 3 / 8 / 16 (D) Water Purification Systems..Produce water with flow rates of 3, 8, 16 l / h respectively...designed to be in compliance with CLSI CLRW quantitative specifications...fit any lab and can be mounted on a bench, wall or floor stand...remove dissolved gases from final product water using Millipore s patented technology. Features..Easy to use...advanced water quality monitoring...complete bacterial control...50 % water savings...quiet operation...consumable cartridges snap in and snap out without special tools...traceability data is archived and allows these systems to be accredited by regulatory bodies. Compliance with Regulatory Industry Standards AFS and Elix Clinical systems are UL and cul listed under file E in the Laboratory Use Electrical Equipment Category, and meet the requirements of UL standards. They also have Class One Medical Device Status under FDA citation 21 CFR AFS systems conform to European Union CE directives 89 / 336 / CEE (electromagnetic compatibility) and 72 / 23 / CEE (electrical equipment within certain voltage limits). All systems are manufactured in ISO 9001 and ISO certified environments. Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. In addition, it may be used in water baths, weatherometers, laboratory dishwashers and autoclaves. WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 33

34 Elix Clinical Water Purification Systems..Produce 35 and 70 l / h..designed to be in compliance with CLSI CLRW quantitative specifications...self regenerating resins using the patented Elix technology, provide significant operating cost savings and ease of maintenance...reduce polishing cartridge changes five-fold. Features..Total control of all functions, operating parameters and standard accessory components within the Elix system itself and within the external pure water distribution loop..patented Elix electrodeionization module continuously regenerates ion-exchange resins..built-in resistivity and TOC (Total Oxidizable Carbon) monitoring to ensure water quality..no additional softeners are required for most feed water conditions..easy-to-replace pretreatment packs, tailored to the feed water source..built-in UV lamp for bacteria-sensitive applications..systems contain integrated control functions for distribution loop components (pump, UV lamp, ASM, TOC and resistivity meters) Applications The water produced by these systems may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. In addition, it may be used in water baths, weatherometers, laboratory dishwashers and autoclaves. It may also be used as the pretreatment step for an ultrapure water system. 34 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

35 BioPak C Polisher Final in-line purification step to remove alkaline phosphatase for immunoassay and clinical chemistry analyzers The.BioPak.C.unit.is.a.disposable.ultrafiltration. cartridge.that.provides.a.final.in-line.purification.step. for.immunoassay.and.clinical.chemistry.analyzers..the. cartridge.is.designed.to.minimize.alkaline.phosphatase. (ALP).released.by.bacteria.that.may.be.present.in.analyzer. feed.water.used.to.dilute.reagents,.make.blanks.and.rinse. tubing.and.probes..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. Features...Produces.ALP-free.water.with.bacteria.levels.lower. than.10.cfu/ml.(typically.<.1.cfu/ml)...creates.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 WATER PURIFICATION systems ADAPTED TO specific NEEDs 35

36 OPTIMIzED PURE WATER storage The main concern when storing purified water is the degradation of water purity over time. Only a strict adherence to suitable reservoir materials, associated with careful design and appropriate protection against airborne contaminants, can ensure consistent water quality during storage. 30, 60 and 100 l PE Reservoirs...Polyethylene.selected.for.minimal.release.of. extractables....blow-molded.technique.associated.with.best.material. choice.prevents.biofilm.formation....cylindrical.shape.minimizes.surface.area.in.contact. with.water....conical.bottom.allows.complete.cleaning.and.rinsing....purified.water.smoothly.fed.in.at.bottom.of.the. reservoir.prevents.absorption.of.carbon.dioxide....uv..an.essential.feature.to.keep.bacterial.levels.low....front.valve.for.manual.dispense.of.purified.water....hermetically-sealed.lid.prevents.air.from.entering.the. reservoir....large.top.opening.allows.cleaning.during.sanitization. procedure....compact,.space-saving.design. SDS 200, 350 l Storage and Distribution Systems Millipore.SDS.200.and.350.liter.reservoirs.incorporate. the.most.advanced.technological.developments.and. innovative.features.to.guarantee.consistent.purity.of.the. stored.and.distributed.water....polyethylene.reservoir.ensures.minimal.release.of. organics.and.smooth.inner.surface.prevents.biofilm. formation....conical.bottom.guarantees.no.dead.volume.and.allows. complete.cleaning,.draining.and.rinsing....asm.(automatic.sanitization.module).uv.lamp.easily. added.to.minimize.bacterial.growth.during.storage....sanitary.overflow.in.the.unlikely.event.of.water.system. malfunction....choice.of.vent.filters.to.protect.stored.water.against. airborne.contamination....sensor.rod.float.switch.for.automatic.reservoir.refill....built-in.pump.option.can.distribute.purified.water.to. multiple.locations....inlet.and.outlet.connections.and.valves.are.all. pre-plumbed.for.easy.installation. 36 WATER PURIFICATION systems ADAPTED TO specific NEEDs

37 Automatic Sanitization Module (ASM) and Water Sensor nm.low.pressure.mercury.vapor.UV.lamp,.selected. for.its.germicidal.effectiveness....pre-programmable.intervals.of.10.min./.day.automatic. UV.illumination.for.optimized.efficiency....Additional.programmable.and.manual.UV.exposure. possible.to.meet.critical.application.requirements....up.to.60.min./.day.of.uv.exposure.for.total.flexibility....choice.of.language.display.and.real.time.clock.for. maximum.convenience....the.asm.is.available.with.an.optional.water.sensor,. which.can.isolate.the.water.system.from.the.main.line. should.any.leakage.be.detected..the.asm.display.will. show.the.time.and.date.water.was.detected.along.with. instructions.on.how.to.use.this.function. ASM Water.Sensor Advanced Protection Against Airborne Contamination A B 1 C Air.is.contaminated.by.carbon.dioxide,.particles,. microorganisms,.and.volatile.organic.compounds.that. come.mainly.from.the.laboratory.atmosphere.itself..to. protect.the.purified.water.from.all.these.contaminants,. Millipore.has.developed.an.advanced.vent.filter.that. includes:...activated.carbon.to.adsorb.volatile.organics.(including. lab.solvents.such.as.acetone,.chloroform.and.methanol)...a.soda-lime.bed.to.remove.co 2...A.Durapore.hydrophobic.membrane.for.particle.and. bacterial.retention D Airborne Contaminants A Volatile Organics B Particles C Bacteria D CO 2 Volatile Organics absorption CO 2 removal Particle and Bacterial retention Reservoir inlet Purified air enters the reservoir This.advanced.vent.filter.is.recommended.for.the. protection.of.high-resistivity.water,.such.as.elix.product. water,.during.storage..a.standard.0.65.µm.membrane. vent.filter.is.available.to.protect.reverse-osmosis-quality. water. 5.Advanced.Vent.Filter.Protects.Water.Purity. WATER PURIFICATION systems ADAPTED TO specific NEEDs 37

38 Type I Water Technologies Used to Produce Type I Water The production of ultrapure (Type I) water demands a combination of different water purification techniques, each removing specific contaminants. Ion-Exchange Resin Ion-Exchange Resins are small (< 1.2 mm) porous beads with ion-exchange binding sites covalently bound on the surface and inside the beads. Millipore Jetpore ion-exchange resins are characterized by high-binding capacity, fast ion-exchange kinetics to reach high resistivity and low TOC release. Ion-Exchange Resin Synthetic Activated Carbon Synthetic activated carbon is produced by the controlled pyrolysis of porous polystyrene beads. The activated carbon has a large developed surface (> 1000 m 2 / gram) and binds organic molecules on the walls of the pores by Van der Waals forces such as hydrophobic interactions. Synthetic activated Carbon UV Photooxidation Lamps UV lamps at 185 and 254 nm wavelengths provide the energy required to convert the oxygen dissolved in water into hydroxyl radicals. These powerful oxidizing agents will transform dissolved organics, first into charged molecules, and ultimately into carbon dioxide. Carbon dioxide will react with water to generate bicarbonate and carbonate ions that can be removed by ion-exchange resins. H 2 O 2 O 2 2 O * UV.(185) 3 O 2 2 O 3 UV.(254) UV.(254) 4 OH * H 2 O 2 O 2 2 H 2 O 2 CO 2 H 2 O H 2 CO 3 CH 3 OH 2 OH * HCHO 2 H 2 O 2 OH * HCOOH H 2 O 2 OH * CO 2 2 H 2 O H H CO- 3 UV Photooxidation Lamps 38 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

39 Microfiltration Membranes Microfiltration membranes are screen filters that retain all contaminants (particulates and bacteria) larger than their pore size on their surface. Millipore membrane filters such as the Millipak filter have been validated for sterilizing filtration and are delivered with a certificate of quality. Microfiltration Membranes Ultrafiltration Membranes Ultrafiltration membranes used in Millipore water purification solutions are hollow fibers that provide a large surface within a small volume and therefore supply the required flow rate with minimum space occupancy. Millipore Pyrogard 5000 and BioPak UF devices have been validated for the efficient removal of pyrogens and nucleases (RNases, DNases). In addition, UF membranes also retain most colloids on their surface. These water purification techniques are organized in an optimized process sequence to make sure that the highest water purity level is reached. Intermittent recirculation of the water allows water quality to be maintained between sampling times to ensure that the quality remains unchanged until the user needs it. The materials that make up the lab water system and are in contact with the water are carefully selected to guarantee minimum release of both ionic and organic contaminants. Hollow Fiber Membranes WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 39

40 Ultrapure Water Systems Milli-Q Integral Water Purification System One water system two water quality types The right water quality for all lab activities. The Milli-Q. Integral system includes a comprehensive, optimized sequence of water purification and monitoring technologies in a single unit, allowing both pure and ultrapure water to be produced directly from tap. It provides pressurized, bacteria-free water through E-POD (Elix-Point-of-Delivery) units and Milli-Q ultrapure water through Q-POD (Quality-Point-of-Delivery) units. Water can be delivered from the system s exclusive production unit to as many as 3 independent PODs that can be conveniently located at different places in the laboratory. Each POD incorporates a color backlit screen enabling the user to check the operation of the entire system and the water quality at a glance. The ergonomic design of the PODs accounts for the height and shape of regular laboratory glassware to ensure optimum user convenience. Water can be delivered at different flow rates from the mobile dispenser located at the end of an 80 cm recirculation loop. The user can also select a specific water volume and have the Q-POD / E-POD unit automatically fill any laboratory vessel from a 100 ml Erlenmeyer flask to a 5 l calibrated flask or 20 l carboy. To ensure easy adaptation to various laboratory applications, validated POD Pak polishers are available to remove contaminants that can impact specific applications (such as pyrogens, nucleases, bacteria, particulates, organics, etc.) just before water leaves the system. Configurations can easily evolve to match lab activity changes or extensions. 40 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

41 Specifications The Milli-Q Integral system is designed to be fed by potable tap water as described in US-EPA, EP and WHO norms. Pure (Type II) water quality Elix water (at Elix module outlet) Parameter Value Unit Resistivity > 5 25 C TOC < 30 ppb (µg/l) Features..Pure and ultrapure water is available directly from tap water (no need to have a DI source in the lab) from. 60 l / day up to 350 l / day (depending on model)..consistent production of superior quality pure water (better than twice the quality of distilled water) without the need to regenerate a DI tank, thanks to patented Elix technology..easy pure or ultrapure water delivery in different lab locations thanks to the PODs..Easy and intuitive operation..application-specific water qualities through customized final polishers..built-in resistivity and TOC monitors designed to comply with the most demanding norms, including USP requirements ( 643 and 645)..System manager-specific interface with protection of key set points by a login and password Applications When the system is equipped with a 0.2 µm filter, the high purity water delivered by the system is suitable for HPLC, LC-MS, MALDI-ToF-MS, IC, ICP, AA and most of the analytical techniques commonly used in the laboratory. When an ultrafiltration cartridge (BioPak) is utilized at the point-of-use, the water is suitable for genomics applications (quality at least equivalent to DEPC-treated water) and cell culture. The water produced following the system s pretreatment step may be used for basic laboratory needs, such as buffer and reagent preparation, microbiology media preparation, histology, dissolution testing (with UV detection) and rinsing of glassware. Note:..If pure water is sourced from an E-POD, the following water quality specifications are achieved: Parameter Value Unit Bacteria < 1 * cfu / ml Particulates > 0.22 µm < 1 * Particulates / ml Pyrogens (endotoxins) < ** EU/ml RNases < 0.01 ** ng/ml DNases < 4 ** pg/ µl * With Millipak filter with Millipore Express membrane or BioPak filter as POD Pak ** With BioPak filter as POD Pak Resistivity, TOC and bacteria levels match the requirements of Type II water as described in ISO 3696, ASTM D1193 (Type II resistivity, TOC, HBC Table I specification), and Purified Water as described in USP, EP. Ultrapure (Type I) water quality Milli-Q water (sourced from a Q-POD unit) Parameter Value Unit Resistivity C TOC < 5 ppb (µg/l) Bacteria < 1 * cfu / ml Particulates > 0.22 µm < 1 * Particulates / ml Pyrogens (endotoxins) < ** EU/ml RNases < 0.01 ** ng/ml DNases < 4 ** pg/ µl * With Millipak filter with Millipore Express membrane or BioPak filter as POD Pak ** With BioPak filter as POD Pak The Milli-Q Integral system is designed to produce ultrapure water in agreement with the quantitative specifications of Type I water as described in ISO 3696, ASTM D1193, and of EP and USP Purified Water, as well as the CLSI - CLRW. WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 41

42 Direct-Q 3 Water Purification Systems Ultrapure (Type I) water directly from tap The Direct-Q 3 system is designed for simple and intuitive operation. Water quality parameters (resistivity or conductivity, temperature) are clearly indicated on a bright color display. The Direct-Q 3 systems allow delivery of a fixed volume of Type I water and automatically shut off once the selected volume has been delivered. The Type I product water is suitable for most low-volume laboratory applications, including the preparation of buffers for liquid chromatography separations and biochemical experiments, of solutions for analytical techniques such as spectrophotometry and spectroscopy, and of culture media. For applications requiring very low organic contaminant levels, the Direct-Q 3 UV system also incorporates a dual wavelength UV lamp to produce water with <5 ppb TOC, making it suitable for HPLC, GC, ILC and TOC analyses. With the BioPak cartridge as a final filter, Direct-Q 3 systems produce pyrogen-free, RNase-free water for cell culture and molecular biology applications. Features..Ideal for laboratories that do not have easy access to pretreated water and need between 1 and 10 l of ultrapure water per day...alarm warning in case of a sudden drop in the quality of the product water...dispensing adapted to different size laboratory glassware...time-saving fixed volume dispense. Applications The ultrapure water produced by the Direct-Q 3. system may be used for regular laboratory applications, such as the preparation of buffers and solutions for titrations, spectrophotometry, atomic absorption or emission spectroscopy, ILC and GC when the final filter is a Millipak, and for life science applications, such as protein and nucleic acid isolation, ELISA tests, electrophoresis gel and buffer preparation, capillary electrophoresis and preparation of media for microbiological, plant and mammalian cell culture when the final filter is a BioPak. The ultrapure water produced by the Direct-Q 3 UV. system is adequate for chromatography applications: HPLC, LC, LC/MS, GC-MS and GC when the final filter is a Millipak Express 20, and for molecular biology applications, when a BioPak is used as the final filter. Specifications Ultrapure (Type I) Product Water Quality* Parameter Typical Value Resistivity, MΩ.cm at 25 C 18.2 TOC. (Direct-Q 3 system) TOC. (Direct-Q 3 UV system with 185 / 254 nm UV lamp) Particulates Bacteria ** Pyrogen *** RNase *** < 10 ppb < 5 ppb < 1 Particulate / ml < 1 cfu / ml < EU / ml < 0.01 ng / ml DNase *** < 4 pg / µl Flow Rate. (w / Millipak Express 20 filter or BioPak cartridge) 0.5 l / min * In regular operating conditions **..With Millipak Express 20 (0.22 µm) membrane filter or with BioPak ultrafiltration cartridge as final polisher ***Only with BioPak ultrafiltration cartridge as final polisher 42 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

43 Direct-Q 5 Water Purification Systems Ultrapure (Type I) water directly from tap The Direct-Q 5 tap-fed water purification system is designed for scientists who need up to 100 l of pure. (Type III) water per day and 5 to 15 l of ultrapure water per day and do not have easy access to acceptable quality pre-treated water. This compact, silent system produces 5 l / hour of pure (Type III) water and up to 0.6 l / min of ultrapure (Type I) water on demand, directly from potable tap water. Direct-Q system performance characteristics are automatically monitored by pressure, temperature and resistivity sensors, and are clearly shown on the system s display, which also indicates when routine maintenance should be performed. Features..Progard plug-in pretreatment pack..constant water flow-rate..automatic refilling of the 10 l reservoir..quiet operation Applications The ultrapure water produced by the Direct-Q 5. system may be used for regular laboratory applications, such as the preparation of buffers and solutions for titrations, spectrophotometry, atomic absorption or emission spectroscopy, ILC and GC when the final filter is a Millipak, and for life science applications, such as protein and nucleic acid isolation, ELISA tests, electrophoresis gel and buffer preparation, capillary electrophoresis and preparation of media for microbiological, plant and mammalian cell culture when the final filter is a BioPak. Specifications Parameter Typical Value Resistivity, MΩ.cm at 25 C 18.2 TOC, ppb with Quantum IX < 30 TOC, ppb with Quantum EX < 10 Particulates 0.22 µm sterilizing filter Type I water flow rate (l / min) Up to 0.6 Type III water flow rate (l / hour) Up to 5 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 43

44 Milli-Q Advantage Water Purification System High qualiy ultrapure water for all critical laboratory applications The Milli-Q Advantage system simplifies your daily life in the lab by utilizing two distinct components:..the Milli-Q production unit is a compact system that can be placed either on the bench, under the bench or on a wall wherever it best suits you...the Q-POD (Quality-Point-of-Delivery) unit provides final polishing at the point-of-use delivering ultrapure water adapted to your specific needs. The revolutionary Q-POD technology empowers you with convenient and flexible dispensing options. Up to three. Q-POD units can be used with each Milli-Q Advantage system at different locations within the same laboratory. Depending on the application, simply select the appropriate media to remove the specific contaminants that may affect your results. For example, the Millipak filter with the Millipore Express membrane (0.22 µm) produces particulate- and bacteriafree ultrapure water for analytical applications such as spectrophotometry, spectroscopy and chromatography. The BioPak ultrafilter, while removing particulates and bacteria, produces pyrogen- and nuclease-free ultrapure water for biochemical applications. 44 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

45 Features..Separation of production and delivery for better laboratory space occupation and easier system installation..multiple and independent water delivery points (Q-POD unit): up to 3 different ultrapure water qualities available in the same lab...improved water purification strategy: the most critical purification step for a specific application is performed by POD Pak consumables just before water leaves the system...water delivery adapted to specific laboratory needs: from low flow to high flow or using the automatic volume dispense function..automatic consumables traceability: using RFID technology, the lab water system automatically registers in its memory the catalogue number, lot number of new Q-Gard and Quantum cartridges installed...built-in Resistivity and TOC meters ensure that both inorganic and organic contaminants remain within specs. The meters are designed taking into account the requirement of USP suitability tests (USP $ 645. and $ 643)..Complete qualification support for laboratories concerned by validation Parameter Typical Value Resistivity 18.2 MΩ.cm at 25 C * TOC < 5 ppb * Particulates (> 0.22 µm / ml) < 1 particulate / ml ** Bacteria < 1 cfu / ml ** Pyrogens (endotoxins) < EU / ml ** RNases < 0.01 ng / ml ** DNases < 4 pg / µl ** Flow Rate up to 2 l / min * *Feed within specifications **Test conditions with the appropriate Q-POD final polisher. Applications This system delivers high purity water suitable for most applications. Equipped with a 0.2 µm filter, the system delivers water suitable for HPLC, LC-MS, MALDI-ToF-MS, IC, ICP, AA and most of the analytical techniques commonly used in the laboratory. When an ultrafiltration cartridge (BioPak) is utilized at the point-of-use, the water is suitable for genomics applications (quality at least equivalent to DEPCtreated water) and cell culture. WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 45

46 Milli-Q Century Range Water Purification Systems This range of Milli-Q systems produces ultrapure water from Elix and RiOs systems water, as well as distilled or. DI water. Each system is designed for specific applications. Applications..The Milli-Q Academic system produces water adequate for regular laboratory applications such as the preparation of buffers and solutions for titrations, spectrophotometry or spectroscopy, atomic absorption or emission, ILC,GC...The Milli-Q Gradient system delivers water recommended for chromatography applications: HPLC, LC, LC/MS, GC-MS,GC...The Milli-Q Biocel system delivers water for life science applications such as protein and nucleic acid isolation, ELISA tests, electrophoresis gel and buffer preparation, capillary electrophoresis and preparation of media for microbiological, plant and mammalian cell culture...the Milli-Q Synthesis system is designed for production of water for critical molecular biology applications such as defined culture media preparation for mammalian (including human) cell culture, preparation of buffers for 2 D Electrophoresis and blotting (Northern, Southern, Western), preparation of solutions for PCR and DNA Sequencing and MALDI-TOF (= Matrix Assisted Laser Desorption Ionisation - Time Of Flight MS)...The Milli-Q Element system is designed for elemental ultratrace analysis (ppt or sub-ppt level) by techniques such as ICP-MS,FAAS, ILC, etc. Academic Gradient Biocel Synthesis Element Applications Lab applications HPLC Life science Molecular biology Trace analysis Product Water Specification * Resistivity 25 C TOC Level (typical values) (ppb) < Pyrogen Level (EU / ml) NA NA < < NA Bacteria (cfu / ml) < 1 < 1 < 1 < 1 < 1 Particulates > 0.22 µm (P/ ml) < 1 < 1 < 1 < 1 < 1 Flow Rate (l / min) *.Test conditions: Milli-Q system equipped with Q-Gard 1 pack, Quantum EX cartridge, feed water produced by Elix system with resistivity > 1 C, TOC < 50 ppd. Product water quality may vary due to local feed water conditions. **.Consumables have to be ordered separately from the system as their selection will depend on the feed water nature and the laboratary applications. 46 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

47 Synergy Water Purification Systems Ultrapure water from pretreated water for lowvolume critical applications The Synergy system is designed for laboratories that already have access to purified water and need a pointof-use system to supply high quality ultrapure water. The compact design assures easy installation anywhere in your lab, on the bench or wall-mounted. The Synergy system allows delivery of a fixed volume of Type I water and automatically shuts off once the selected volume has been delivered. Features..Quality suitable for HPLC and other spectrophotometric/spectroscopic analytical techniques for biological, biochemical, and cell culture applications...dispensing adapted to different size laboratory glassware...time-saving fixed-volume dispense. Applications The ultrapure water produced by the Synergy system may be used for regular laboratory applications, such as the preparation of buffers and solutions for titrations, spectrophotometry, atomic absorption or emission spectroscopy, ILC and GC when the final filter is a Millipak, and for life science applications such as protein and nucleic acid isolation, ELISA tests, electrophoresis gel and buffer preparation, capillary electrophoresis and preparation of media for microbiological, plant and mammalian cell culture, when the final filter is a BioPak. The ultrapure water produced by the Synergy UV system is adequate for chromatography applications: HPLC, LC, LC/MS, GC-MS and GC when the final filter is a Millipak Express 20, and for molecular biology applications, when a BioPak is used as the final filter. Specifications Resistivity,. MΩ.cm at 25 C Synergy Synergy UV TOC, ppb < 10 < 5 Flow Rate, l / min Up to 1.2 Up to 1.2 Final Filter 0.22 µm filter or BioPak ultrafilter 0.22 µm filter or BioPak ultrafilter *..Feed water: Pretreated water (Elix system, RO, distilled or DI water). WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS 47

48 Simplicity Water Purification Systems Personal ultrapure water source The Simplicity portable water purification system can be located anywhere in your laboratory. To use it, simply plug it in, insert the consumable and fill the removable 2 l reservoir with pre-treated water (Elix, RiOs, distilled or. DI water). The Simplicity system will produce Type I water on demand at a flow rate of 0.5 l / min. Features..System draws water from a removable, refillable,. built-in reservoir...alarm function in the event of a sudden drop in the quality of the product water guarantees your water quality at all times...dispensing adapted to different size laboratory glassware. Applications The ultrapure water produced by the Simplicity system may be used for regular laboratory applications, such as the preparation of buffers and solutions for titrations, spectrophotometry, atomic absorption or emission spectroscopy, ILC and GC when the final filter is a Millipak, and for life science applications such as protein and nucleic acid isolation, ELISA tests, electrophoresis gel and buffer preparation, capillary electrophoresis and preparation of media for microbiological, plant and mammalian cell culture, when the final filter is a BioPak. The ultrapure water produced by the Simplicity UV system is adequate for chromatography applications: HPLC, LC, LC/MS, GC-MS and GC when the final filter is a Millipak Express 20, and for molecular biology applications, when a BioPak is used as the final filter. Specifications Simplicity Simplicity UV Resistivity, MΩ.cm at 25 C TOC, ppb < 15 < 5 Flow Rate, l / min > 0.5 > 0.5 Final Filter 0.05 µm filter or BioPak ultrafilter 0.05 µm filter or BioPak ultrafilter *..The Milli-DI system provides a convenient feed water source for Simplicity systems. 48 WATER PURIFICATION SYSTEMS ADAPTED TO SPECIFIC NEEDS

49 Super-Q Plus Water Purification Systems Produce up to 12 l / min of Type I ultrapure water on demand The.Super-Q.Plus.System.is.a.high-flow.water.system. designed.to.provide.the. final.polish.to.water.that. has.been.pretreated.by.reverse.osmosis,.distillation. or.deionization..super-q.plus.systems.consistently. produce.ultrapure.water.quality.which.exceeds.type.i. ASTM./.CAP./.CLSI.specifications. The.Super-Q.Plus.water.system.features.a.modular.design. for.the.production.of.ultrapure.water..the.system.also. features.automatic.recirculation.of.water.on.an.hourly. basis.to.maintain.water.quality.between.uses.. Features...Modular.design.for.the.production.of.ultrapure.water.....Automatic.recirculation.of.water.on.an.hourly.basis.to. maintain.water.quality.between.uses.....because.super-q.product.water.is.produced. on. demand,.there s.no.need.to.store.water.and.risk. degrading.water.quality.over.time. specifications Parameter Typical Value Flow.Rate,.l./.min Resistivity,.MΩ.cm.at.25. C 18.2 TOC,.ppb * <.20 Microorganisms,.cfu./.ml ** <.10 Heavy.Metals,.ppm <.0.01 Silicates,.ppb <.0.01 Total.Dissolved.Solids,.ppm <.0.03 Electrical.Requirements. Pump./.Motor:.0 33.H.P. 120.V./.60.Hz.or. 230.V./.50.Hz *.With.the.Organex-Q.cartridge.installed.and.feed.water.pretreated. by.reverse.osmosis. **With.Durapore.cartridge.installed WATER PURIFICATION systems ADAPTED TO specific NEEDs 49

50 Point-of-use purifiers Millipak Filter Units For bacteria filtration of liquids in pharmaceutical applications The.Millipak.Express.40.filtration.unit.is.built.using. the.stacked.disc.filters.concept..the.microfiltration. membrane.is.sealed.to.a.solid.support.in.order.to.warrant. its.integrity.during.the.filtration.process..a.total.of.four. membrane.discs.are.bonded.to.two.supports.to.reach.a. total.200.cm 2.filtration.surface..The.stacked.disc.design. allows.minimal.hold-up.volume.and.particle.shedding,. making.millipak.units.ideally.suited.for.high.value-added. applications. The.Millipak.Express.40.filter.unit.housing.is.made.of. SAN.to.avoid.the.release.of.plasticizers.that.are.clearly. identified.as.endocrine.disrupters.such.as.bisphenol.a. The.Express.0.22.µm.membrane,.validated.for.bacteria. removal,.has.conical-shaped.pores.to.ensure.a.high.flow.at. a.low.differential.pressure.and.is.heat.welded.on.the.san. support.to.avoid.the.release.of.chemicals.in.the.water. The.Millipak.Express.40.filter.is.the.last.purification.step. of.a.milli-q.water.system..it.is.therefore.critical.to.ensure. that:...it.efficiently.removes.the.contaminants.that.it.is. supposed.to.retain.(particulates,.bacteria)...it.does.not.add.unwanted.contaminants.(ions,.organics,. particulates).to.the.purified.water This.is.ensured.by.a.strict.quality.insurance.process,. including.an.in-depth.validation.followed.by.regular.qa. tests.registered.in.the.certificate.of.quality.delivered. with.each.millipak.express.40.filter.unit..for.instance,. each.unit.is.integrity.tested.during.manufacture.to. guarantee.its.efficiency. 50 WATER PURIFICATION systems ADAPTED TO specific NEEDs

51 BioPak Polisher Final purification step at the ultrapure water pointof-delivery provides pyrogen- and nuclease-free water The.BioPak.unit.is.a.disposable.ultrafiltration.cartridge. typically.used.in.cell.culture,.biochemistry.or.molecular. biology.applications..it.can.be.installed.at.the.outlet.of. Type.I.water.purification.systems.such.as.the.Milli-Q,. Direct-Q,.Simplicity.or.Synergy.systems,.to.produce. pyrogen-.and.nuclease-free.ultrapure.water.for.a.period. of.up.to.three.months. Features...Direct.connection.to.all.Millipore.Type.I.water.systems....Pyrogen-free.water.(< EU./.ml).production....RNase-free.water.(<.0.01.ng./.ml).and.DNase-free. water.(<.4.pg./.µl).production....safe.method.that.eliminates.the.need.to.treat.water. with.depc....bacteria-free.water.(<.1.cfu./.ml).production....warranty.of.results.within.specifications.for.a.minimum. of.90.days.usage....maintenance-free. EDS-Pak Polisher Endocrine disrupter-free water at the ultrapure water point of delivery The.EDS-Pak.polisher.is.a.disposable.point-of-use. ultrafiltration.cartridge.developed.by.millipore.to.meet. the.needs.of.researchers.who.require.ultrapure.water. free.of.endocrine.disrupters.(eds)..the.eds-pak.polisher. can.be.installed.on.all.millipore.type.i.water.purifi.cation. systems.that.deliver.ultrapure.water.with.toc.<.5.ppb,. including.the.milli-q.synergy,.simplicity.and.direct-q. systems..it.is.designed.to.provide.at.least.300.l.of. EDS-free.ultrapure.water.before.replacement.is. necessary.. Features...Point-of-use.polisher.for.use.with.Milli-Q.and.other. Millipore.Type.I.water.purification.systems....Final.purification.step.provides.endocrine. disrupter-free.ultrapure.water.at.high.flow.rate when. you.need.it....delivers.a.minimum.of.300.l.of.eds-free.ultrapure.water....validated.for.efficient.removal.of.bisphenol.a,.diethyl. phthalate.and.di-n-butyl.phthalate....each.eds-pak.cartridge.is.delivered.with.a.certificate. of.quality WATER PURIFICATION systems ADAPTED TO specific NEEDs 51

52 Service Solutions Providing Expert Support and Peace of Mind Millipore s Certified Field Service Support Engineers provide expert, professional support for the installation, validation and maintenance of both individual water systems and total water systems. We also offer design and engineering support for larger volume central systems requiring pretreatment, storage, and distribution to multiple points-of-use. visit for the most up-to-date product listing

53 Preventive Maintenance 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. 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 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. Service Solutions 53

54 Support and Expertise

55 Technical Support Millipore s In-house Support Team is available to answer any questions you may have on your water purification system. Our specialized team is always ready to help. Project Management From needs assessment, design and installation services, to system qualification and user training, Millipore provides comprehensive project management throughout to ensure that all bases are covered. This includes. hands-on assistance with the water purification system design and installation, selection of the necessary materials and components, as well as assistance with budget planning and providing a detailed quotation package. Design and Engineering Millipore designs the water purification installation to meet a customer s exact specifications. The design includes the water purification system as well as the storage, distribution and control systems. Millipore s engineering group has a broad selection of systems and accessories available (such as storage reservoirs, distribution pumps, UV lamps, warning systems, and control and measuring equipment) and the required expertise to design the system to meet your specific needs. Training Support Millipore regularly organizes seminars worldwide covering water purification techniques, removal of contaminants and how to optimize the installation of your water purification system. You can inquire about participating in a scheduled Millipore seminar on our web site. Our Application Specialists or Field Service Support teams can also provide on-site customized training. Give us a call, send an or visit our web site anytime.. ( Scientific Support Millipore brings you scientific support every step of the way. Our Lab Water Application Experts will guide you through the process of selecting the most suitable system for your requirements. Then throughout the lifetime of your Millipore equipment, you will benefit from our scientific support, technical assistance, R&D application support teams and range of technical and scientific literature technology briefs, detailed product specifications, technical posters and our R&D Notebook publications summarizing the research carried out by our scientists on new water purification developments. Support and Expertise 55