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BV200 Plasma Viscometer Mk2/3 Customer User Manual

BV200 Plasma Viscometer Mk2/3 Customer User Manual

BV200 Plasma Mk2/3 Customer User Manual

Overview

The Benson Ltd BV200 clinical viscometer is a capillary viscometer for in vitro use in the , designed and calibrated to measure the of human (or animal) blood plasma and other clinical . The BV200 is manually loaded and unloaded with blood samples and reagent tubes. The operation is automated so that it measures patient samples and carries out automated check quality controls every ten patient samples without manual intervention offering a walk away operation. It is intended for use in clinical by trained laboratory professionals testing potentially high- risk blood samples, so it is designed to handle bio-hazardous materials safely. All equipment is manufactured, produced and supplied by Benson Viscometers Ltd, in the UK. Only reagents and viscometer cleaning products that are produced and supplied by Benson Viscometers are to be used with the analyser. The key clinical applications are in the identification and monitoring of chronic inflammatory conditions, for example rheumatoid arthritis and in the monitoring of malignancies of the immune system, e.g. myeloma and to determining hyperviscosity.

Contents

1. Company Contact Information ...... 2 2. Viscometer Specification ...... 3 3. Health and Safety Warnings ...... 9 4. System Overview...... 18 5. Draft Standard Operating Procedure (SOP) ...... 20 6. User Maintenance ...... 23 7. Quick Start Guide ...... 47 8. Barcode Reader Programming ...... 49 9. Reagents and Samples ...... 50 10. Zero run time: High value viscosity determination on the BV200 ...... 51 11. Plasma Viscosity Clinical Interpretation ...... 52

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1. Company Contact Information

For all Enquiries please call us on 01646 650065 or e-mail: [email protected]

Benson Viscometers Ltd Benson Viscometers Ltd Unit H – North Estate 13 Greenwich Business Park Withybush Road Greenwich Close Haverfordwest Ipswich SA62 4BS Suffolk IP3 0DD

Registered Office Benson Viscometers Ltd. Croft Quarry West Williamston Pembrokeshire SA68 0TN

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2. Viscometer Specification 2.1. Operating Environment Conditions The BV200 viscometer is designed to be used in a clinical laboratory.

UK Configuration 230 - 240 volt 50Hz A/C single-phase mains electricity Voltage US Configuration 110 - 120 volt 50/60Hz A/C single-phase mains electricity

There are 3 electrical connection points on the BV200: Input/output  Main IEC input socket Electrical  RS232 (Male) connection for communication with the PC Connections  RS232 (Female) connection for communication with the pump assembly sensors.

There are 3 non-electrical connection points on the side of the Input/output BV200 Non-Electrical  4mm tube push fit connector for the wash Connections  5mm tube push fit connector for the vacuum regulator  6mm tube push fit connector for the waste bottle

Current 3 amps peak

Operational 10-27°C. temperature The system heats up the sample to 37°C during testing

Humidity 20-70%

Normal atmospheric pressure (1 atm).

Atmospheric The equipment is not affected by static atmospheric pressure, but pressure may be influenced by changing atmospheric pressure, which will require the system to be recalibrated – this can be done automatically or manually, depending on customer preferences.

Vibration Vibrating equipment such as centrifuges may significantly affect Viscometer the performance of the equipment. It is strongly recommended Specification that such equipment is not placed on the same bench as the BV200 viscometer.

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2.2. Supply Connection UK Configuration -The BV200 viscometer is connected to the 230 volt mains supply via a 5 Amp fused IEC cable (supplied). The UK plug is plugged in to any mains outlet with the ratings above and the IEC connector is then inserted into the power socket on the left side of the unit. US Configuration - The BV200 viscometer is connected to the 115 volt mains supply via an IEC cable (supplied), the plug is plugged to any mains outlet with the ratings above and the IEC connector is then inserted into the power socket on the left side of the unit. 2.3. Electrical Protection The „AT‟ power supply unit (PSU) BV200 240-volt mains input viscometer (UK) is fitted with and protected by a 5-amp fuse located in the 3 pin mains plug of the viscometer input cable. The 36-volt PSU, BV200 240-volt mains input viscometer (UK) is fitted with and protected by a 5-amp fuse located in the 3 pin mains plug of the viscometer input cable. The 36-volt PSU viscometer is protected by two 3.15-amp fuses located in the IEC inlet socket. The viscometer is also protected by an over voltage protection circuit located within the 36 volt PSU. The BV200 110 – 120 volt mains input viscometer (US) is fitted with a 36 volt PSU protected by two 3.15 amp fuses located in the IEC socket. The viscometer is also protected by an over voltage protection circuit located within the 36 volt PSU The BV200 240 volt viscometer (UK) vacuum pump bases are protected by a 1 amp fuse located in the plug of the pump base input cord. The pump base assembly mains plug is the disconnecting device and should be plugged into a socket such that it is identifiable and easily reached. For the BV200 pump bases using a “” type vacuum pump (silver) the BV200 also has a power on/off switch at the rear of the pump unit. 2.4. Protective Conductor Earthing Point The protective conductor earthing point is connected to the IEC socket which connects to the mains socket earth via the IEC cable (supplied). The earthing point is located on the inside of the case on the left side panel above the IEC socket. All side panels are connected to the protective conductor earthing point to ensure the equipment is fully grounded.

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2.5. Accessories

Pump assembly consists of: CA B85 Vacuum Pump or R 300 Vacuum pump Vacuum Regulator Pump Assembly Wash and Waste Bottle 4mm 5mm 6mm and 8mm connection hoses Grey PVC base plate with built in liquid level sensors

A computer (PC) that consists of: Monitor PC Computer Keyboard Mouse

2.6. Physical Data

Analyser 35 Kg Weight Base unit 9 Kg

Analyser 42cm high x 55cm wide x 57cm deep Size Base unit 40cm high x 35cm wide x 30cm deep

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2.7. Performance Characteristics

Linear Range The viscometer has a linear range from 0.89 – 9.99mPa.s

Imprecision / To minimise imprecision the viscometer is calibrated and Uncertainty / quality control checked with standards that are fully traceable Repeatability and to the British National Physical Laboratory (BNPL), Reproducibility Teddington, England. The BNPL uncertainty data is available on request. Instrument uncertainty is a measurement of its accuracy. When a patient sample is presented at the test point, the barcode of the sample will be read by the barcode reader and the sample will then progress to be tested. If the result of this sample is outside the preconfigured limits (default 1.4- 2.0 mPa.s) the sample will automatically be retested. If the result of the second test is within ± 5% of the first test carried out on the sample, the initial result will be accepted by the viscometer and is then transmitted (pending approval if set up for manual sign off). This also ensures viscometer result repeatability The second result is stored in the viscometer but marked as void for LIMs and it is not transmitted. The 1.6mPa.s check control (is measured every ten patient samples), the control 2.5, control 4.0 and the high and low calibrator reagents have their plasma viscosity (PV) value encoded within the barcode on their tubes. When these reagents are presented to the analyser, their barcode is read and the reagent is tested. In the case of the high and low calibrator reagents, this is an optional functionality and requires configuration. The result of the reagent test is compared to the value encoded for that reagent and if it is within ± 5% of that value, the analysis is accepted. An uncertainty report for the check and the control 2.5 is available within the results menu. In the UK, The National External Quality Assessment Service (NEQAS) confirms result reproducibility by a monthly analytical monitoring service producing an independent audit for all participating laboratories.

Interference There are no known interferences with the plasma viscosity result. * Please see Interpretation of Results for further information.

Carryover Under normal conditions the carryover between samples, calibrators and controls should be <0.01mPa.s.

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2.8. Uncertainties and Linearity

Viscosity Range Dynamic Viscosity mPa.s (cP)

0.3 to 7.4 ± 0.07 %

7.4 to 10 ± 0.09 %

10 to 30 ± 0.12 %

The chart above shows the BV200 viscometer test linearity from 0.89 to 9.99 mPa.s. The PV was measured at 37℃ but reported at 25°C

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The chart above shows the BV200 viscometer test linearity from 0.69 to 6.34 mPa.s. The PV was measured at 37℃ and reported at 37C.

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3. Health and Safety Warnings The following are recommendations for safe operating of the BV200 Viscometer. They should be used in conjunction with your local Health and Safety procedures. 3.1. Symbols used within this documentation

Symbol Meaning

Caution – consult the documentation for more information on the warning This symbol is essentially a safety symbol and should be used to highlight the fact that there are specific warnings or precautions associated with the device, which are not otherwise found on the label

Potentially deadly – treat with extreme caution

Toxic – treat with extreme caution

Biological Hazard – treat with extreme caution

Gloves must be worn

Harmful – treat with extreme caution

Laser Reader – treat with extreme caution

Biological Waste – treat with extreme caution

Electrical items – possibility of electrical shock

Anti-static electrical items which can be damaged by static electricity

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3.2. General Warnings

Type of Warning Precaution

Blood samples deteriorate with time Blood samples for plasma viscosity testing can and incorrect storage temperature be used for up to 7 days. It is recommended the plasma sample be separated from the whole

blood. Plasma samples should be stored at ambient room temperature and should never be stored in a fridge or freezer. If plasma is stored in a fridge, cryoproteins will precipitate out of the leading to incorrect results.

Blood products can carry blood borne All operators are required to be trained in infection. handling contaminated blood products. Always wear properly fastened protective laboratory clothing when operating the equipment - this is especially true of wearing protective gloves.

The Anti-Biological Growth Reagent The anti-biological growth reagent used is toxic if undiluted comprises 0.02% Sodium Azide in the LOW, HIGH, and CHECK reagents, so is not toxic at this level but users should be aware of the hazard.

All those who are likely to come into contact with this reagent should take the precautions listed in the MSDS supplied with the support documentation.

The cassette probe is sharp and Avoid all contact with the probe tip. should always be considered as a Wear surgical gloves whenever handling the Biohazard cassette and probe. Fit probe guards when removing the cassette and ensure probe guards are fitted at all times the probes are not installed in the viscometer, apart from when it is being cleaned.

The Viscometer contains moving Never operate with loose fitting clothing - always parts wear properly fastened protective laboratory clothing when operating the equipment Long hair should be restrained. During operation never have the plastic door to the cassette open. Never operate the viscometer with the main front hinged cover up.

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Type of Warning Precaution

The Viscometer contains a laser The laser reader beam used by viscometer reader barcode readers has a low power output. Do not look directly into the beam. The laser is a class 2 product with a maximum output radiation of 1 mW. The emitted wavelength is 630-680 nm to IEC 825-1 (1993)

Waste bottle for the Viscometer The Waste bottle and its contents should be contains Biohazard products treated as hazardous and handled according to your organisation's health and safety policy. When carrying out the scheduled sterilise maintenance process on the waste bottle, always wear suitable safety clothing as indicated in your organisation‟s health and safety policy. In the UK it is recommended to follow the Committee of Substances Hazardous to Health (COSHH) requirements for the chemicals used in your organisation.

General use of the Viscometer for Please follow the instructions provided in this measuring viscosity on Blood Plasma document when using the BV200, failure to follow these instructions could cause harm, injury or illness. The company cannot be held responsible for any unwanted effects that arise from misuse.

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3.3. Electrical Warnings

Type of Warning Precaution

Electrical supply Although fully tested before shipping it is advisable that you have your viscometer checked by a competent electrical contractor before use.

Electrical Power Supply Cord Do NOT replace the detachable MAINS supply cords with an inadequately RATED cord. An adequately rated cord should comply with the following:

UK - IEC (C13)/US-IEC (C13) HO5VV-F 3G 1.0mm² Cores Fitted with 5amp fuse (UK only) GTSA-3 N1458

The unit must not be operated with Never operate the equipment with any of the the hinged front cover up. cover(s) raised up or removed.

Cleaning the viscometer with water Only trained operators should clean the could increase the hazard of an viscometer. electric shock. Cleaning fluid should never be used near the electrical components of the system especially those behind the lift-up hinged front cover of the viscometer. It is perfectly safe to clean the stage and drive mechanism underneath – normally done as part of the monthly cleaning activities.

If incorrect actions are taken, there Only trained personnel are permitted to maintain or is a risk of electric shock during repair the viscometer. maintenance. Before opening any covers always disconnect from the power supply unless the power is required for diagnosis.

Circuit boards are used in the Touch an earth point immediately before viscometer. They can be damaged attempting to handle a circuit board. by static electricity. Keep any circuit board in an electrostatic bag when not in use/fitted.

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Type of Warning Precaution

Do not subject the PC or The PC is not rated to be used in wet/humid Viscometer to wet or humid conditions. As a guide please see lab conditions conditions. for use in this document.

Vacuum Pump will not start when Do not leave the vacuum pump powered on if it powered up. does not start. There may be residual vacuum retained in the waste bottle and the pump may fail to start. The vacuum pump may overheat causing a hot paint or electrical smell. If the vacuum pump does not start immediately, disconnect the power and release the residual pressure in the waste bottle. If the pump still fails to start, switch it off at the plug and contact the Benson Viscometers support desk.

3.4. Cleaning Warnings

Type of Warning Precaution

When removing and handling a Always switch the analyser off before cassette it must be considered to be removing/replacing the cassette. a Biohazard Always decontaminate a used cassette and probe after changing the cassette. Gloves, safety goggles and a lab coat should be worn as a minimum. Always fit the plastic sleeve to the probe as soon as possible after removing the cassette from the viscometer.

Waste from the Viscometer contains The waste bottle and its contents should be small amounts of blood products. treated as though it contains blood products and handled according to your organisation's health and safety policy. Gloves, safety goggles and a lab coat should be worn as a minimum. When adding sterilising agent(s) to the waste, always wear safety clothing as indicated in your organisations health and safety policy. In the UK it is recommended to follow Committee of Substances Hazardous to Health (COSHH) requirements of the chemicals used in your organisation.

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3.5. Maintenance Warnings

Type of Warning Precaution

There is a risk of electric shock Only trained personnel are permitted to maintain during maintenance. or repair the viscometer. These personnel must not access any parts with mains voltages. Before opening any covers always disconnect from the power supply unless the power is required for diagnosis. Only qualified electricians are permitted to work on parts which could have lethal voltages.

Blood Products are Biohazard liquids All those maintaining the viscometer are required to be instructed on the precautions to avoid becoming infected by blood products.

The Anti-Biological Growth Reagent The anti-biological growth reagent used is toxic if undiluted comprises 0.02% Sodium Azide in the LOW, HIGH, and CHECK reagents, so is not toxic at this level but users should be aware of the hazard.

All those who are likely to come into contact with this reagent should take the precautions listed in the MSDS supplied with the support documentation.

3.6. Moving/Positioning the Viscometer We do not recommend the viscometer is moved or relocated by anyone other than a trained Benson Viscometer engineer.

Type of Warning Precaution

The Viscometer main unit weighs 35kg The BV200 is too heavy for a single person.

Packaging There is no standard packaging provided with the viscometer. Care is needed when moving the viscometer to ensure no damage occurs to it.

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Type of Warning Precaution

Positioning the Viscometer The viscometer must be positioned so that it is possible to operate the disconnecting device (green switch on side of unit, or mains plug switch). The viscometer must not be located where vibration can affect its operation e.g. where a centrifuge is on the same bench or on a neighbouring connected bench. The viscometer should be located in an environment which has a constant temperature and as per the operating environment conditions earlier in this document. Do not locate the viscometer next to an opening window or in direct sunlight as temperature variations can affect result repeatability.

3.7. Transport considerations There is no standard packaging for the BV200. The unit is normally delivered by Benson Viscometers engineers. Be aware that the unit is heavy (35Kg) and should be regarded as a 2-person lift.

The analyser is heavy – 35Kg and should not be lifted by 1 person

It is recommended that you contact the Benson Viscometers Support Desk where we can offer a costed viscometer relocation service to decontaminate, decommission and relocate with minimal local assistance, then set-up and fully re-commission the viscometer including a fully documented and certificated acceptance procedure, leaving the viscometer in a ready to use condition.

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Benson Viscometers will move the unit safely using the following instructions: 1. Safely remove all connections to the BV200 consisting of: a. 2 x grey communications cables b. 3 x clear waste and vacuum tubes c. 1 x power cable 2. Ensure all standard and patient tubes are removed from the viscometer 3. Ensure all doors and panels are closed and secured with screws where appropriate 4. There are no feet/castors on the bottom of the instrument so care must be taken when lifting and placing so as to not trap fingers. 5. Two persons are required to move a BV200 viscometer – each should stand either side of the instrument with one hand under the sample rack and other under the main BV200 body, it is good practice to slide the instrument forward so the front 20-25cm over hangs the work surface, a hand can then be placed underneath and gently lift the front of the instrument up so that the hand to support the rear of the unit can then be placed under the instrument. 6. Benson Viscometers will then safely relocate the viscometer to the required location and connect and commission the analyser. 7. Once commissioned, Benson Viscometers will carry out an acceptance procedure and supply a documented acceptance report before testing patient samples can be commenced. 3.8. Cassette and probe warnings The cassette is delivered to sites using a hard case with foam cassette shaped cut-outs. This should have a caution and a biohazard sign on it. The case will arrive with a security tie and test security seal label. The security tie and label should not be broken until such time as the cassette is required for use. A test certificate is enclosed confirming calibration and performance.

Cassette probes are sharp The cassette should be regarded as a biohazard.

3.9. Circuit Boards Warnings

The circuit boards within the BV200 should be regarded as sensitive to static.

When printed circuit boards are being transported, it is recommended that they are wrapped in an antistatic bag with a static warning label on it. A suitable strong well-padded container or box should be used.

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3.10. Barcode Reader Warnings The barcode reader contains a laser reader. Do not look directly at the beam. It is a class 2 laser product with a maximum output radiation of 1 mW. The emitted wavelength is 630-680 nm to IEC 825-1 (1993)

The barcode reader contains a laser reader.

3.11. EMC Statement The BV200 complies with the emission and immunity requirements described in documents IEC61326-1 and 61326-2-6. The device is classified as Group 1 Class A, as specified in CISPR 11:2009, Clause 5. It does not emit any dangerous or significant RF energy. As a precaution however, the following phrase is brought to the users‟ attention: “This equipment has been manufactured and tested to CISPR 11 Class A. In a domestic environment it may cause radio interference, in which case, you may need to take measures to mitigate the interference.” As a general precaution, the electromagnetic environment should be evaluated prior to operation of the equipment. If in doubt, please consult the Benson Support Desk. Do not use this device in close proximity to sources of strong electromagnetic radiation (e.g. unshielded intentional RF sources), as these can interfere with the proper operation. 3.12. IVD Statement The BV200 is an IVD (In Vitro Diagnostic) device for use in a clinical laboratory environment. It is not a personal self-testing device. 3.13. Disposal or Decommissioning of the Viscometer

Type of Warning Precaution

The Viscometer and its A viscometer or any part or sub component must be component parts are to be decontaminated before transporting or disposal. considered a Biohazard Benson Viscometers is committed to the WEEE Directive and as such will decommission, decontaminate, collect and, when suitable will recycle viscometer components that are useful and serviceable.

Please contact the Benson Viscometers Support

Desk for more information.

The Anti-Biological Growth The anti-biological growth reagent used comprises Reagent is toxic if undiluted 0.02% Sodium Azide in the LOW, HIGH, and CHECK reagents, so is not toxic at this level but users should be aware of the hazard.

Before disposal, the viscometer must be cleaned and certified as free of toxic contamination. This also applies to any parts being disposed of.

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4. System Overview 4.1. Principle The Benson automated plasma viscometer uses a regulated vacuum to pull fluid samples through a calibrated capillary tube to determine a fluids viscosity. The precise time of the fluid passage between two predetermined positions and the capillary tube is measured and the fluid viscosity calculated. 4.2. Viscometer system overview

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4.3. Pump base

4.4. Viscometer

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5. Draft Standard Operating Procedure (SOP) 5.1. Before operating the viscometer 1. Empty and rinse the 4 litre waste bottle. 2. Empty and rinse the condensation bottle. 3. Ensure the wash container is emptied, rinsed and then refilled daily with fresh wash. Wash = 2 litre distilled or de-ionised water with 1 barcoded wash additive. 4. All viscometer covers and panels should be fitted and closed. 5. The control vac regulator (sample vacuum) should be between -0.4 and -0.45 bar. 6. Do not adjust the regulator unless followed by a full manual calibration 7. The vacuum on the waste bottle vac gauge should be a minimum of -0.7 bar. (70% vacuum). 8. Make sure the cap on the waste bottle is fully tightened and the air tubes are fully plugged in. 5.2. To test centrifuged EDTA plasma samples

- Ensure all samples to be tested are fully centrifuged (note – controls do not need to be centrifuged)

- Allow all samples and calibrators to stabilise their temperature to room temperature before testing. This will take longer if samples have arrived by post or from a courier.

- Do not store PV samples in a fridge. Plasma samples should be stored at room temperature and should never be stored in a fridge. If plasma is stored in a fridge, cryoproteins will precipitate out of the fluid, leading to incorrect results.

- All calibration and patient sample tubes should be inserted so that the bar code labels are aligned with the marker on the carriage tube holder.

- All tubes must be fully pressed down in the holder to avoid tube crashes in the test area.

1. Insert a charged CHECK tube with cap on in the first green holder 2. Place centrifuged sample tubes into the black holders, starting after the first CHECK tube. 3. Insert a charged CHECK tube in each green tube holder as the viscometer is filled. 4. Insert a charged CHECK tube in the green tube holder after the last patient sample. Note: If a known High-Risk sample/s are tested (run as a batch), follow it with a viscometer STERILISER tube placed before the stop flag. 5. Insert a „stop flag‟ behind the last CHECK tube. 6. To start sample analysis, left-click on the viscometer screen button marked „Start‟. Top left 7. Samples and CHECK calibrators may be added at any time. Move the stop flag to the end of the sample line. 8. The viscometer can be set to automatically retest a CHECK which has not been validated.

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9. If the second check is not validated the viscometer will either STOP or automatically RECALIBRATE, depending on the choice of configuration. The „STOP‟ (manual calibration) option is recommended, since it allows the operator to investigate and carry out possible local maintenance if required. To carry out a manual calibration insert the following charged calibration tubes in the next available carriages:- Red carriage for HIGH CALIBRATOR with cap OFF Blue carriage for LOW CALIBRATOR with cap OFF Green carriage for CHECK CALIBRATOR with cap OFF (Check cap off for calibration only). To initiate a manual calibration press „manual calibration‟ in the „maintenance menu‟ 10. After testing the liquid, sample tubes should be removed from the conveyor. 11. Remove any „empty‟ HIGH, LOW, and CHECK tubes. These can be identified by looking at the schematic display showing the distribution of all tubes that have been tested. Empty tubes will have their symbol (e.g. C) flashing. In the barcode column on the screen there is a number showing the number of dips taken from each calibration tube (12 dips per tube for CHECK and 6 dips per tube for HIGH and LOW). 12. Reposition the CHECK tubes (12 dips per tube) to green holders on the left of the tube conveyor as the viscometer is loaded with patient samples. 13. Insert an empty HIGH tube in the red holder. This will update the viscometer tube location software as to the position of the red holder no 199 in the stage. The viscometer can count and record the tube carrier numbers as the conveyor advances. 14. On completion of work select a „closedown clean‟ or insert a „stop flag‟. This will initiate a closedown clean which will drain the wash water from the valves and the fluid system. 5.3. To print a results report 1. There are a number of reports available within the software such as;  Results reports  Useage reports  Levey-Jennings analysis of CHECKS/CONTROLS  Uncertainty analysis of CHECKS/CONTROLS 2. These are found in the results menu of the software

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3. Specific records can be displayed and selected for printing.  If no specific record is chose, all records will be printed.  To select more than one consecutive record that you wish to print, hold the SHIFT key down, and select the start and end rows.  To select more than one non-consecutive record, hold the CTRL key down, and select the individual rows. 4. Once the required records have been selected, click the printer icon on the right hand side of the results headed line. 5.4. To stop the viscometer during operation In an emergency or if you need to stop the viscometer rapidly, turn off the green power switch on the left side of the viscometer. Before switching the viscometer back on, wait at least 10 seconds. This allows retained power within the viscometer power supply to dissipate. To stop the viscometer after samples have been processed, Benson Viscometers recommends a stop flag is inserted into the black carriage after the last sample in that batch to be tested. The system will perform a close down clean after it has read the stop flag barcode and will then stop. Alternatively, click on the button marked „Stop‟ on the control screen. The system will acknowledge the stop request and the instrument will stop only after the next operation has been completed 5.5. Powering off the equipment If the viscometer has been stopped using the "Stop" button, a closedown clean will need to be initiated by clicking the button on the main screen or within the maintenance menu. It is recommended that the viscometer and pump are left powered on to maintain the viscometer at a stable operating temperature, reducing the temperature fluctuations that arise as a result of the unit being powered off and on. The system will then remain ready for immediate use following the required maintenance.

All spare parts and consumables must be supplied directly from Benson Viscometers Ltd.

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6. User Maintenance

The waste container and contents should be considered a biohazard

Do not routinely use Sodium Hypochlorite or bleach products.

A trained user is required to perform the following daily, weekly and monthly maintenance. For all other maintenance issues please contact Benson Support.

6.1. Daily Maintenance

1. From the status menu located at the top centre of the screen, click in the box below the “Daily” cleaning (change 2 boxes to add menu)

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2. Follow the on-screen instructions to empty/refill the waste and wash

The waste container and contents should be considered a biohazard.

It is recommended that Benson Viscometer cleaning agents are used.

a. When using Benson Viscometers cleaning agents i. Select “Single” or “Bulk” additive as appropriate

ii. Select “Scan Barcode”, Then scan the barcode on the single use tube or bulk additive, using the viscometer handheld barcode scanner

iii. Alternatively enter the barcode manually by selecting “Manual Entry” and use the keyboard to type the barcode from the single use tube or bulk additive

iv. When complete select “Click to Proceed”

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b. It is recommended that Benson Viscometer cleaning agents are used, however, when not using Benson Viscometers cleaning agents. i. Tick the box “Disable Wash Additive barcode check at this time”

ii. Enter initials

iii. When complete select “Click to Proceed”

3. Follow the on-screen instructions. . Using the provided tube labels, Insert 1 full (mixed) ENZYME tube (protein digestive cleaner) immediately followed by 1 STERILISER tube For instructions on making up the Enzyme and Steriliser Solutions please see section 6.5 and 6.6.

a. When using Benson Viscometers cleaning agents i. Select Enzyme tube “Scan Barcode”, Then scan the barcode on the bulk Enzyme bottle, using the barcode scanner

ii. Alternatively enter manually by selecting “Manual Entry” and use the keyboard to type the barcode from the bulk Enzyme bottle

iii. Select Steriliser tube(s) “Scan Barcode”, Then scan the barcode on the bulk Steriliser bottle, using the barcode scanner

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iv. Alternatively enter manually by selecting “Manual Entry” and use the keyboard to type the barcode from the bulk Steriliser bottle

v. When complete select “Click to Proceed”

b. It is recommended that Benson Viscometer cleaning agents are used. However, when not using Benson Viscometers barcoded cleaning agents you will need to seek approval to override this feature from a Senior within the laboratory. This can be completed as per the below instructions. i. Tick the box “Disable Enzyme Additive barcode check at this time”

ii. Enter initials

iii. Tick the box “Disable Steriliser Additive barcode check at this time”

iv. Enter initials

v. When complete select “Click to Proceed”

4. Follow the on-screen instructions and add any additional notes

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a. When complete select “Click to Finish”. The viscometer will then process the Enzyme and Steriliser tubes.

Note: This process takes approximately 25 minutes to complete

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6.2. Weekly maintenance 1. Click in the “Weekly” days or due area from the cleaning activities section in the top bar or from the maintenance manu.

2. Follow the on-screen instructions to remove and clean the washpot

a. When completed select “Click to Proceed”

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3. Follow the on-screen instructions to remove and clean the drain line filter

a. When complete select “Click to Proceed”

4. Follow the on-screen instructions to inspect and clean the probe Always remove the probe from the cassette before cleaning.

You will need a Benson probe cleaning rod, a cloth soaked in a sterilisation fluid and a plastic tube cover guard for the probe.

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a. Instructions: i. Starting position. Remove the probe from the cassette using the probe removal tool.

ii. Clean the capillary with the cloth soaked in sterilisation fluid. iii. Under running water take the probe, and gently insert the probe cleaning rod into the top. Move the rod up and down several times, or until any deposit stops being forced through the aspiration hole.

iv. Inspect the holes in the probe to ensure they are clear and clean if necessary, using a pin. Note: do not use a pin or other such device when the probe is connected to the cassette. There is a piece of plastic tubing going through it called the capillary - if you push a sharp item through the holes and through the capillary the system will not work correctly.

Take particular care to ensure the holes are clear at the small breather hole just up from the aspiration hole.

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b. When complete select “Click to Proceed”

5. Follow the on-screen instructions to check and adjust the capillary When looking at the aspiration hole, identify how much of the capillary is visible and is occupying the hole. Ideally, the capillary should only just be visible as in the top picture below. If you are unable to adjust the capillary, the system will continue to operate as long as the capillary does not occupy more than half of the aspiration hole.

a. When complete select “Click to Proceed”

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6. Follow the on-screen instructions to check and clean the waste bottle cap with a cloth soaked in laboratory sterilisation fluid. Some staining of the rubber seal is normal and acceptable.

a. When completed select “Click to Proceed”

7. Follow the on-screen instructions and add any additional notes

a. When complete select “Click to Finish”. The viscometer will then start the decontamination clean process

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8. Scan the decontamination additive used or enter the barcode manually

a. When using Benson Viscometers cleaning agents i. Select “Single” or “Bulk” additive as appropriate

ii. Select “Scan Barcode”, Then scan the barcode on each single use tube or the bulk additive, using the barcode scanner

iii. Alternatively enter manually by selecting “Manual Entry” and use the keyboard to type the barcode from the single use tube or bulk additive

iv. When complete select “Click to Finish”

a. It is recommended that Benson Viscometer cleaning agents are used. However, in the event Benson Viscometers cleaning agents are not used, you will need to seek approval to override this feature from a Senior within the laboratory. This can be completed as per the below instructions. i. Tick the box “Disable Decontamination Additive barcode check at this time”

ii. Enter initials

iii. When complete select “Click to Finish”

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9. Follow the on-screen instructions for Decontamination Clean Stage 1 once

a. When complete select “Press here to continue”

10. Follow the on-screen instructions for Stage 2

a. When complete select “Press here to continue”

Note: The system will automatically complete stages 3-6 of the decontamination clean process

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11. Follow the on-screen instructions for Stage 7

Note: You do not need to empty and refill the wash and waste bottle if already completed as part of the weekly maintenance above

a. When complete select “Press here to continue"

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6.3. Monthly maintenance 1. Click in the “Monthly” cleaning from the top bar

2. Follow the on-screen instructions to clean the carriages

a. When complete select “Click to Proceed”

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3. Please remove the three stage side panels using the black finger screws. Inspect the sump filter and clean as required. Follow the on-screen instructions to rinse the base

a. To drain the fluid from the base area, open the “Sump Drain” by clicking on the Sump Drain button. This process can be repeated if necessary, to fully drain all the fluid

b. When complete select “Click to Proceed”

4. Follow the on-screen instructions to empty/refill the waste and wash bottles

The waste container and contents should be considered a biohazard.

a. When complete select “Click to Proceed”

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5. Follow the on-screen instructions and add any additional notes

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6.4. Manual decontamination process The manual decontamination cleaning process comprises 7 stages.

Warning: Do not routinely use bleach products when cleaning/decontaminating the viscometer as this can impact the serviceability of the viscometer system components. We recommend using Benson Viscometers barcoded decontamination additive, shown below.

1. From the Maintenance Menu on the main screen select do Decontamination Clean

2. The following popup will be displayed, with the following text:- Add the barcoded decontamination additive to 118ml of demineralised.

Screw on the Decontamination bottle cap.

Remove the wash tube from the top of the and connect it into the tube adaptor on the Decontamination bottle cap.

a. Replace and screw on the decontamination bottle cap. b. Remove the wash tube from the top of the wash bottle and connect it into the tube adaptor on the decontamination bottle cap.

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c. Once complete click the Press here to continue button

3. After the first stage, the next popup will be displayed, with the following text:- Empty the decontamination liquids from the waste and condensation bottles then rinse each with fresh (tap) water very well. Remove the wash tube from the Decontamination bottle cap tube adaptor and re-connect to the Wash Bottle.

Pour approx. 100ml of tap water into the carriage area near the front of the BV200 unit, so it drips down into the drainage channels below the carriages to flush the sump valve.

4. At the last stage, the final popup will be displayed, with the following text:- Empty the liquids from the Wash, Waste, Decontamination, and Condensation bottles. Rinse all four bottles very well with fresh (tap) water. If required for testing, refill the 2 litre Wash Bottle with the normal amount of wash fluid (2 litres of demineralised water and 1 tube of wash additive or bulk additive as directed)

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5. Once complete click the Press here to continue button

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6.5. Enzyme Cleaning

1. How to Prepare Enzyme Cleaning Fluid

Mix 3 drops of the enzyme cleaner concentrate with 4 ml of de-ionised water (1:50 ratio) in a sample tube with an enzyme label. Replace the cap and mix well. Remove the cap and introduce the tube to the viscometer along with the steriliser tube (see below) to complete the daily maintenance. Discard any enzyme not used. The concentrate is supplied in a 30 ml dropper container. We estimate this dropper will last up to 10 months. The concentrate remains stable until it is mixed with water when it then has a 14 day use by date. As the enzyme is only mixed when it is needed this should not be an issue.

2. To Commence Enzyme Cleaning

An enzyme clean will commence when a tube displaying an „ENZYME‟ label is read by the barcode reader on the viscometer. The probe will go into the Enzyme tube and then extract all of the Enzyme cleaning fluid. The fluid is retained in the Cassette, Upper Manifold, and Upper Valves for approximately 4 minutes (during this time the Enzyme digests the blood product proteins). The conveyor is then moved and the washpot comes forward and the probe lowered. Enzyme fluid from the upper manifold is transferred to the washpot, drain line and valve, and lower manifold, and held for 18 minutes to work on the washpot. This waiting period can be stopped at any time if necessary. However, this is not recommended. If it is stopped the whole process should be repeated as soon as is practicable.

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6.6. Steriliser Cleaning

1. How to Prepare Steriliser Cleaning Fluid

Mix 4 drops of the Steriliser Additive concentrate with 4 ml of de-ionised water (1:20 ratio) in a sample tube with a Steriliser label. Replace the cap and mix well. Remove the cap and introduce the tube to the viscometer along with the enzyme to complete the daily maintenance. Discard any steriliser not used. For each Steriliser cleansing process, the viscometer will take all of the mixed cleaner from the „Steriliser‟ bar coded laboratory tube. The concentrate is supplied in a 30 ml dropper container. We estimate this dropper will last up to 6 months. The concentrate remains stable until it is mixed with water when it then has a 14-day use by date. As the steriliser is only mixed when it is needed this should not be an issue.

2. To Commence a Steriliser Clean

A steriliser clean will be carried out when a tube displaying a „Steriliser‟ label is read by the barcode reader on the viscometer. The probe will go into the steriliser tube and extract all of Steriliser cleaning fluid. The fluid is retained in the Cassette, Upper Manifold, and Upper Valves for approximately 1 minute (during this time the Steriliser helps to minimise the risk of any harmful pathogen build-up). The conveyor is then moved and the washpot comes forward and the probe lowered. Steriliser fluid from the upper manifold is transferred to the washpot, drain line and valve, and lower manifold, and held for 40 seconds (in 2 steps each of 20 seconds) to work on the washpot. This waiting period can be stopped at any time if necessary. However, this is not recommended. If it is stopped the process should be repeated as soon as is practicable.

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6.7. Probe to Washpot Seal Test To ensure optimal washpot seal performance following the weekly maintenance, please follow the instructions below: 1. Ensure the viscometer is switched on and in a ready for operation state 2. Go to the Maintenance menu on the main screen and open the Service Menu 3. Open the Individual steps tab 4. Bring the Washpot Out by clicking the washpot forward button, then click the move Probe down to Seal Washpot button 5. Open the Valves tab 6. Observe the waste vaccum gauge and make a note of the waste vacuum level. 7. Click on the Drain Valve button whilst observing the waste vacuum gauge 8. The vacuum pressure should only drop by about 0.05 bar and then hold steady. 9. If the vacuum level drops greater than 0.05 bar please Investigate the following: a. The green and black tube connections at the back of the washpot are secure b. The probe is tight on the cassette using the red probe nut spanner c. The capillary tube at the back of the cassette is pushed fully in and secure d. The O-ring seal at the top of the probe is shiny and round and not worn e. The washpot restrictor is in good condition (not cracked) and screwed into the washpot 10. To finish Click on the Return Probe to Top button, then click the Washpot Back button and finally, click the All valves Off Button 11. If any of the points „a‟ to „e‟ have been changed then repeat the full Washpot Seal test.

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6.8. Drain Line Filter Cleaning 1. Remove the inline filter from the drain line between the washpot and the drain valve. 2. Remove the 3mm (black tail) tubing and connector from the cassette cleaning syringe. 3. Fill the syringe with 20ml of de-ionised water. 4. Push the 4mm (green tail) tubing into the top green coloured part of the filter. 5. Flush the entire contents of the syringe through the filter ensuring that the waste is going in to a dirty sink. 6. If debris remains in the filter repeat steps 3 – 5. 7. Fluid can pushed and sucked through the blue connection on the filter, using the syringe, to remove any stubborn particles. 8. IMPORTANT – Flush the cassette syringe after use to remove any contamination and debris to prevent this being injected into the cassette during cleaning.

Syringe

Fill the syringe with de-ionised water. Flush the entire contents of the syringe via the green connector through the filter.

Luer adaptor

Green coded 4 mm ø tube

Flow

Drain Filter

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6.9. Short volume samples Low volume, „short samples‟ can be tested on the BV200 Viscometer. Here are some solutions used by different laboratories depending on the tube type and consumables available. For 75 x 13 ml tubes transfer only a small amount of plasma 0.4 to 0.5 ml (maximum) to a 1.5 ml hanging cup or 1.5 ml mini tube using a Pasteur. Place the hanging cup or mini tube in an empty primary tube. Apply a barcode to the big tube for identification if possible. It is very important that the plasma sample level is not higher than the primary tube label. A pointed bottom mini tube is preferred as it will accommodate the pointed tip of the cap piercing probe better.

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7. Quick Start Guide  Empty Waste, Fill Wash (2 litre distilled water and 1 barcoded Wash Additve) empty and rinse Condensation bottle  Check Regulator is set between -0.40 and -0.45 and Waste Guage at -0.70 minimum  Run Daily, Weekly or Monthly Maintenance as required

 Place a CHECK in the first green holder followed by 10 samples and another CHECK

 Click START, more samples and CHECK calibrators may be added at any time  Place a STOP FLAG at the end of the sample line 7.1. Samples  Allow all samples to stabilise at room temperature before testing. Remember this will take longer if samples have arrived by post or from a courier  Ensure all samples to be tested are fully centrifuged (note – controls do not need to be centirfuged) Do not store PV samples in a fridge. When samples cool some cryoproteins can precipitate out, Centrifugation may then remove this protein content from the sample - leading to an erroneous clinical plasma viscosity result.  If a known High Risk sample is tested, follow laboratory procedure for working with high risk samples and decontaminate the analyser using a STERILISER tube 7.2. Vacuum  When Calibrating use the HIGH and run blind (turn the barcode away so it cannot be read by the barcode reader), adjust the regulator so the runtime is 2.00 ± 0.05  Vacuum on waste bottle vac gauge should be a minimum of; -0.70  Make sure the cap on the waste bottle is fully tightened and the cap tubes are fully inserted 7.3. Probe  The probe air breather holes must be clear (10mm from the aspiration hole at the tip)  Light should be seen directly through the breather holes  Ensure the probe nut fitted to the cassette is as tight as possible using the red probe nut spanner  Ensure the probe tip is centred on the probe target  Probes can be aligned in the viscometer and do not need to be returned. – see Help, section 5.2.3. All broken probes parts should be returned without the cassette, for repair or replacement 7.4. Cassette  The capillary tube connector in the back of the cassette should be secure. It should not be able to be unscrewed easily. If you have a red coloured tube connector, this is permanently fitted so do not try to remove it  The thin plastic tube at the back of the cassette should be pushed fully into the tube connector, through the inner rubber seal until it cannot be pushed any further  Check the penetration of the capillary at the probe aspiration hole. Ensure the capillary end can still be seen but is not out over halfway. A „short‟ capillary end is considered best

7.5. Calibration  Become familiar with calibration High (2.00), Low (1.32), and Check (1.67) run times  Calibrate with the calibrator caps OFF, note any large variations or swings in gradient and offset  BV200 gradient will normally be between 6.0 and 8.0

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7.6. Decontamination  Add the 7ml barcoded decontamination additive to 118ml of demineralised water.  Mix the 125 ml of „decontamination fluid‟ in the Decontamination bottle  Attach to the wash bottle tubing and follow the on screen instructions  Laboratory bleach should not routinely be used on the viscometer or in the system 7.7. Enzyme  Put 4ml of deminerlaised water into an enzyme labelled empty collection tube  Add 3 drops of the concentrated enzyme from the 30ml dropper to the tube  Replace the cap of the tube and mix well  Remove the cap and present the tube to the viscometer barcode reader  The Viscometer will use most of the mixed cleaner. Discard any cleaner left in the tube 7.8. Steriliser  Put 4ml of demineralised water into an Steriliser labelled empty collection tube  Add 4 drops of the Steriliser Additive from the 30ml dropper to the tube  Replace the cap of the tube and mix well  Remove the cap and present the tube to the viscometer barcode reader  The Viscometer will use most of the mixed cleaner. Discard any cleaner left in the tube 7.9. Analysing NEQAS or External QC samples  Centrifuge the samples and treat the same as a patient sample  Apply NEQAS/External QC 01 and 02 barcodes to samples for identification and the verification of records stored in the viscometer PC. This will also help to stop the reporting of „crossed over‟ results to NEQAS/External QC 7.10. Cassette Cleaning  Only use the syringe with the BV Lure adaptor and tube to push wash through the cassette capillary (See section 4.2 in the help files) Never use a Pasteur or syringe nozzle to attempt to squirt liquid directly into the cassette tube connector. Water will inevitably leak and enter into the cassette inner body to destroy the sensitive electronics inside.

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8. Barcode Reader Programming

The Viscometer contains a laser – it is only low level, used to read barcodes. Do not stare into the beam. It is a class 2 laser product with a maximum output radiation of 1 mW. The emitted wavelength is 630-680 nm to IEC 825-1 (1993)

8.1. Procedure

1. Switch on power to the Viscometer 2. Open the front cover of the Viscometer 3. Sweep the barcode strips through the red barcode beam from, „set‟ to „end‟. 4. As the barcode reader scans the „set‟ barcode, the sounder should give 3 audible bleeps.” 5. When reading a code input the sound will change to a continuous 2 syllabul tone (beep-bop). 6. As the barcode reader scans the „end‟ barcode, the sounder should give an additional 3 audible bleeps.” 7. If the sounder gives more than 3 bleeps, or continues to bleep, represent the end of the strip to the reader until 3 audible bleeps are heard.

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9. Reagents and Samples All calibration fluids are supplied by Benson Viscometers Ltd. and should be stored out of direct sunlight in the laboratory at ambient room temperature. 9.1. Check Control 12 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. 9.2. Check Calibrator 12 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. 9.3. Low Calibration 6 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. 9.4. High Calibration 6 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. 9.5. Control 2.5 6 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. 9.6. Control 4.0 6 dip units per Sarstedt 2.7 tube (contains glycerine and Sodium Azide -Toxic) Shelf life: 1 year from fill date - the expiry date is shown on the box and on the tube. Caution: Sodium Azide is toxic, however the percentage contained within the above reagents is small (0.02%). On disposal of any excess calibration and control fluids, flush down your allocated disposal area with water. 9.7. Sample storage. It is recommended to store samples intended for clinical viscosity analysis at ambient room temperature (15-20°C) and do not to refrigerate them. The reason for this is due to the potential for cryoproteins and or cryofibrinogen to precipitate out when the sample becomes cold. Once precipitated cryoproteins frequently do not resuspend and are consequently not sampled by the viscometer leading to an incorrect low result being reported.

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10. Zero run time: High value viscosity determination on the BV200 One reason that a zero-value viscosity is recorded on an individual sample of adequate volume is when the sample has a very high viscosity (e.g. over 10 mPa.s) for the recommended vacuum setting on the viscometer. The BV200 viscometer uses a set vacuum in the determination of a plasma viscosity. This vacuum is adjusted and maintained by the vacuum regulator attached to the vacuum pump on the viscometer pump base. The vacuum should be adjusted to give a test runtime result in the range of 1.90 and 2.10. for the high (2.0mPa.s) calibrant. With the vacuum set as above the detectable viscosity range of the BV200 can be between 0.6 mPa.s and 10 mPa.s. reported at 25°C. To test higher , it is necessary to increase the vacuum that is used to draw the thicker sample through the capillary in the cassette. This procedure instructs an operator how to increase the vacuum and recalibrate the analyser to allow the analysis of samples suspected of having extremely high plasma viscosities. Warning: Do not operate the viscometer during the regulator adjustment process. It is not necessary to disconnect the viscometer or PC from the power supply during the regulator adjustment process. 10.1. Procedure for adjusting the regulator to determine extremely high clinical viscosities 1. Record the reading shown on the vacuum regulator gauge. If possible, mark the position of the needle on the gauge, and the adjustment knob. 2. For regulators with a light grey regulator knob, release the lock on the vacuum regulator valve by gently lifting the knob approximately 3mm out of the regulator body. Regulators with a black regulator knob should adjust freely. For Benson regulators the stem should adjust freely, you may require a 3mm Tommy bar or use an Allen key as a Tommy bar to aid the adjustment. 3. Turn the vacuum regulator adjustment knobs clockwise (viewed from the front or above) while watching the increase in vacuum reading on the vacuum gauge. When the regulator vacuum gauge stops moving up, slowly adjust the regulator valve anti clockwise until the gauge indicates a drop in vacuum from its maximum to approximately -0.1 PSI or -10% vacuum Note: the regulated vacuum needs to be lower than the maximum pump vacuum reservoir in the waste bottle. 4. Lock the light grey regulator knob vacuum regulator valve by pushing it down, no further action needs to be taken with the other knobs. 5. Perform a manual recalibration cycle. 6. When recalibration is complete, place the sample(s) suspected of having a high viscosity on the BV200 and run in the normal manner with a Check calibration before and after the test. 7. After completion of the high clinical viscosity determination, reset the vacuum regulator to its original settings The vacuum should be adjusted to give a test runtime result in the range of 1.90 and 2.10. for the high (2.0mPa.s) calibrant. 8. Perform a manual recalibration to reset the Viscometer to give your normal run times for routine samples. 9. When calibration is complete the BV200 is ready to run routine samples.

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11. Plasma Viscosity Clinical Interpretation Plasma viscosity changes when plasma protein concentrations are altered. The major influences on plasma viscosity are exerted by fibrinogen and immunoglobulins. Fibrinogen responds as an acute phase reactant and is raised in the initial stages of any inflammatory response. In infection, the initial response is followed by an increase in immunoglobulin which will maintain a high plasma viscosity. In some autoimmune conditions e.g. rheumatoid disease, the increased immunoglobulins, along with the raised fibrinogen due to the inflammatory response, can produce a raised plasma viscosity. In early tumour growth, normal plasma proteins and plasma viscosity are seen. When the tumour becomes invasive or disseminated, a rise in plasma viscosity is frequently seen. Conditions that secrete paraproteins e.g. myeloma or macroglobulinaemia are associated with very high plasma viscosity. Untreated myeloma plasma frequently has viscosity values of >3 mPa.s while plasma containing macroglobulins can have values >10 mPa.s. 11.1. Samples Required Plasma from EDTA anticoagulated peripheralvenous blood. 11.2. Sample Storage and Preparation Centrifuge sample at 3500 rpm for 10 minutes, 2000g for 10 minutes, 3000g for 5 minutes or equivalent. Samples can be stored at ambient room temperature (15°C-20°C) for up to 7 days. It is recommended that the plasma is taken off the red cell fraction if practical. 11.3. Interpretation of Results

Normal Range 1.50 – 1.72 mPa.s

Low results <1.50 Found in infants under 3 years old and patients with low immunoglobulin or fibrinogen levels.

Equivocal 1.72-1.75 Frequently found not to be of clinical significance. Results If investigating a clinical condition suggest discussing with clinician and repeat after appropriate time. If found by chance discuss with clinician and suggest monitor patient

High results 1.75 – 2.00 Found in many chronic disorders e.g. Autoimmune diseases infection, malignancy, vascular disease and other causes of inflammation.

Very high results 2.01 – 3.00 Suggestive of myeloma.

Extremely high >3.00 Suggestive of Waldenstrom‟s results macroglobulinaemia.

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* If a patient has recently had a high volume of intravenous fluid administered this may alter the patients viscosity result. For example, some plasma expanders may give erroneous low values, whilst some parenteral fluids may give erroneous high values. 11.4. Physiological Factors Influencing Plasma Viscosity Age (after 3 years), gender, and diurnal rhythms have no effect on PV. Throughout life serial PV measurements in a healthy individual vary as little as 0.05 mPa.s. The only physiological factor that has a significant and consistent effect on PV is pregnancy. PV remains normal in the first two trimesters and gradually rises to around 1.80 mPa.s in the final trimester. Therefore, small variations in an individual‟s PV may be clinically significant. 11.5. Plasma Viscosity in Disease 1. Acute phase response As a result of the acute phase response many plasma proteins including fibrinogen and immunoglobulins are increased and this is reflected as a rise in PV. This response occurs within 24 hours. 2. Chronic inflammatory diseases PV cannot diagnose any condition; however, when taken in conjunction with a clinical assessment a result in the range of 1.75 – 2.00 mPa.s can give an indication of an underlying problem. 3. Malignant disease Early stage malignancy may be associated with a normal PV. With more advanced disease there is often a moderate rise in PV. 4. Paraproteinaemias This group of disorders can be associated with markedly raised PVs and such patients may display symptoms of hyperviscosity syndrome (confusion, visual disturbance, epistaxis, difficulty breathing, renal impairment). In general, IgM paraproteins are associated with much higher PVs than IgG and IgA paraproteins, but this is not absolute because IgG and IgA molecules may polymerize and lead to very high PVs. NB: a normal PV does not exclude a diagnosis of a paraproteinaemia because of instances of light chain only or non-secretory myeloma. 5. Severely ill patients In severely ill patients (e.g. in intensive care) impaired synthesis and/or increased degradation of plasma proteins may lead to a fall in PV. This should not be taken as an indication of an improvement in the patient‟s underlying condition in this situation. 6. Covid-19 It has been established that Covid 19 patients who develop severe symptoms have a marked rise in plasma viscosity. Unconfirmed social media items suggest some patients may develop a raised serum viscosity.

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