UNYVERO System Manual Rev 6 March 2017

No part of this manual may be reproduced in any form or translated into other languages without prior permission and written consent of Curetis GmbH.

Curetis GmbH Max-Eyth-Str. 42 71088 Holzgerlingen Germany phone +49 (0)7031 / 4919 5 10 Fax +49 (7031) 4919 5 19 (hereafter referred to as “Curetis”)

Last updated: 05 / 2017 Please contact Curetis (if assistance is provided directly by Curetis) or your local contact regarding the current print edition. Unyvero is a registered trademark of Curetis.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

Table of Contents UNYVERYO SYSTEM INSTALLATION AND SET-UP

INTRODUCTION 1.1 1.2 1.3 1.4 1.5

Patents Symbols Used Conventions Used Liability Service and Support

6 6 7 8 9

SAFETY 2.1 2.2 2.3 2.4 2.5

Responsibilities of the User Instrument Safety Electrical Safety Environmental Information Chemical and Biological Safety

11 12 13 14 14

UNYVERO SYSTEM 3.1 Overview 3.2 Unyvero L4 Lysator 3.3 Unyvero Cartridge 3.4 Unyvero A50 Analyzer 3.5 Unyvero C8 Cockpit 3.6 Symbols Used 3.7 Analysis Principle 3.8 Unyvero Operating Software (OS) 3.9 Unyvero Lysator Displays 3.10 Unyvero Analyzer Displays

© Curetis GmbH, 2017

16 18 19 20 21 22 22 23 27 27

4.1 Preparation 29 4.2 Installation 31 4.3 Device Registration and Deregistration 32 4.4 Setting Up the Unyvero System 34 4.5 Additional Functions of the Unyvero System 37 4.6 Test Preparation 40 4.7 Uninstallation 41 4.8 Decontamination 42

CLEANING AND MAINTENANCE 5.1 Cleaning and Disinfection 5.2 Maintenance

44 45

ERROR MESSAGES 6.1 Error Messages

49

TECHNICAL DATA 7.1 7.2 7.3 7.4

Electrical Specifications Environmental Conditions Transport and Storage Dimensions

Unyvero System Manual

Item No. 00117 Rev. 6.0

52 52 53 53

INTRODUCTION

6 This is an operating manual for the Unyvero System and should only be used by qualified personnel.

1.1 Patents The Unyvero System is protected by the following patents: Singapore Patent No. 185467; Aust. Patent No. 2011254936, Chinese Patent No. ZL201180024484.8

1.2 Symbols Used Safety Symbols WARNING A warning contains information relating to tasks that, if not performed correctly, could result in injury to the user or even death. Follow instructions that include a warning only once you have understood the risk and can therefore carry out the task without risk of injury. CAUTION A caution contains information relating to tasks that, if not performed correctly, could result in damage to the product or invalidate the results of the analysis. Please do not carry out any tasks until you have understood the potential risk involved and can therefore perform the task correctly. NOTE Notes are pieces of information that make it easier to work with the product more efficiently and effectively.

Interactive soft keys are shown in bold.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

7 1.3 Conventions Used Short Names Table 1 Unyvero Components

Full Names

Short Names

Unyvero A50 Analyzer

Unyvero Analyzer

Unyvero L4 Lysator

Unyvero Lysator

Unyvero C8 Cockpit

Unyvero Cockpit

Unyvero M1 Master Mix Tube

Unyvero Master Mix

Unyvero Operating Software

Unyvero OS

Unyvero Cartridge

Unyvero Cartridge

Unyvero Application Plug-In

Unyvero Plug-In

Unyvero Sample Tube Holder

Sample Tube Holder

Unyvero Sample Tube

Sample Tube

Unyvero Sample Tube Cap

Sample Tube Cap

Unyvero Transport Cap

Transport Cap

The Unyvero System consists of the Unyvero Analyzer (item no. 60001), the Unyvero Lysator (item no. 60002), the Unyvero Cockpit (item no. 60003), including the Unyvero OS Software, and the Unyvero Sample Tube Holder (item no. 60010). The Unyvero Application uses the following components: The Unyvero Cartridge, the Unyvero Sample Tube, the Unyvero Sample Tube Cap, the Unyvero Master Mix Tube, and applicationspecific Unyvero Plug-In software.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

8 The Unyvero Application is always indication-specific. Each application is described in the respective manual.

1.4 Liability The content of this manual is subject to change by Curetis at any time without prior notice. All data and information in this application manual has been compiled in accordance with current German law, European standards and directives. Curetis gives no guarantee or warranty, either with regard to this manual (in any form of presentation or distribution) or its products. This also applies to marketability, applicability to a particular purpose and the non-infringement of third-party intellectual property rights. Curetis will provide immediate notification if any conflicting rights come to light. Curetis accepts no liability for damage caused as a result of: » improper installation by a person other than Curetis itself » failure to comply with the operating manual supplied with the instruments and the cartridge » use of the devices or cartridges for applications other than the approved indication » untrained staff, or » modifications to the products Curetis » is liable for any negligence or willful misconduct in the event that key contractual obligations are breached. Depending on the amount, liability for negligence is limited to the amount of the order. Liability for consequential damage and financial losses (e.g. loss of profit) is excluded in the case of negligence. » is otherwise liable only for damage to materials or property caused by intent or gross negligence. Depending on the amount, liability for negligence is limited to the amount of the order. Liability for consequential and financial losses (e.g. loss of profit) is excluded in the case of negligence. The aforementioned liability limitations and exclusions do not apply to claims brought under the Product Liability Act, claims due to fraudulent behavior of a contractual partner, liability claims for guaranteed quality characteristics, or damages resulting from injury to life, body or health.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

9 1.5 Service and Support If your region is under Curetis customer care, please contact Curetis support by phone or email. Have the serial number of your devices at hand (located on the rear of the Unyvero Cockpit and the Unyvero Lysator, and under the front cover of the Unyvero Analyzer). Phone +49 (0)7031 / 4919 5 55 (Monday-Friday from 9 a.m. to 5 p.m. CET) or email: [email protected]. For all other regions, please contact your local contact person.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

11 This chapter provides information on how to use the Unyvero System safely and describes the safety precautions that need to be taken.

2.1 Responsibilities of the User The Unyvero System is approved for the detection of pathogens, antibiotic resistance genes, and toxin markers. Detailed information regarding the specific Unyvero Applications can be found in the application-specific manuals. CAUTION The Unyvero System may only be used for its intended purpose. Curetis assumes no responsibility for the use of the Unyvero System for any other purposes. Before using the Unyvero System, every user must be instructed on how to operate the instruments. This training is only to be conducted by Curetis personnel or by persons trained by Curetis. In addition, the user should have read the manuals for the respective Unyvero Application and all relevant material safety data sheets (Unyvero Cartridge, Unyvero Sample Tube, and Unyvero Sample Tube Cap).

Personal Protective Measures WARNING Biological samples can transmit infections. Treat all biological samples, including their sample containers, as potentially infectious. Adhere to your local guidelines regarding the handling of biological material. Wear disposable gloves, a lab coat and safety glasses when handling samples and consumables of the Unyvero Applications. Wash your hands thoroughly after handling patient samples and consumables of the Unyvero Applications. Discard used consumables according to local safety guidelines, or instructions of your local regulatory authority.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

12 2.2 Instrument Safety The products are shipped in a condition that guarantees technical safety and otherwise complies with safety regulations. This manual contains information and warnings that every user must follow to ensure safe use and maintenance of the product. WARNING If this product is not used as described, the intended safety measures may not be effective. This could result in a contamination with potentially hazardous substances. Use this product only as described in the Curetis manual. Read also the relevant safety information in the respective Unyvero Application manual. Damaged or faulty devices entail the risk of an electric shock. If a device appears to be damaged or defect, it must be decommissioned immediately and disconnected from the power supply until it is repaired by a qualified Curetis specialist, or a person trained by Curetis. Incorrect installation and initial operation may result in life-threatening situations or property damage. Installation and initial operation may only be conducted by Curetis personnel or authorized representative. Do not set-up the instruments yourself. Contact Curetis support, if you need assistance. Never remove instrument covers. Incorrect lifting may result in painful, lasting back injury. Depending on weight, moving or lifting of instruments may necessitate up to four persons. Do not attempt to move or lift the instruments without help or appropriate equipment. Movable instrument parts may cause bruising or cuts. Keep your hands away from movable Unyvero Lysator parts and opened Unyvero Analyzer slots. Place only sealed Unyvero Sample Tubes into the Unyvero Lysator, and only insert Unyvero Cartridges into Unyvero Analyzer slots. CAUTION Apart from air filters, Unyvero instruments and consumables do not have any parts that require maintenance by the user. If any servicing is necessary, it should only be conducted by Curetis or specialists authorized by Curetis.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

13 2.3 Electrical Safety WARNING Working with instruments without cover has the inherent risk of serious electrical shock. Therefore, never remove instrument covers. Contact Curetis support or your local contact person in case you need servicing. Unsuitable cleaning procedures increase the risk of electrical shock. Always disconnect instruments from their power supply before cleaning. Follow cleaning and decontamination instructions in section 5.1. Incorrect grounding holds the risk of electrical shock. Put the power plug only into a socket with protective earthing contact. Do not use extension cords without protective conductor. Operation of an electrical device in the presence of flammable gases or vapors poses a safety hazard. NOTE The Unyvero System corresponds to overvoltage category II and air pollution level 2. The Unyvero System can be operated using a single-phase AC power source between 110 V and 240 V (10% maximum voltage fluctuation) and in a frequency range of 50 to 60 Hz. Maximum power consumption is: » » »

Unyvero Analyzer 400 W Unyvero Cockpit 120 W Unyvero Lysator 240 W

In compliance with international safety standards, the system is classified as a class 1 safety product; thus the devices have a three wire power cable with protective conductor.

Safety and Electromagnetic Compatibility The instruments were tested and comply with the following norms: IEC EN 61010-1:2001, IEC 61010-2-101:2002, IEC 61326-1:2005, and IEC 61326-2-6, Ed. 1:2005, IEC 61010-2-081:2001 + A1: 2003, EN 61326-1:2005. Also, Unyvero Lysator and Unyvero Analyzer comply with IEC 610102-010:2003, and Unyvero Lysator also with IEC 61010-2-020:2006.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

14 2.4 Environmental Information This product is only intended for indoor use and should only be operated under the environmental conditions detailed in section 7.2.

2.5 Chemical and Biological Safety WARNING Biological samples can transmit infections. Treat all biological samples, including their sample containers, as potentially infectious. Adhere to your local guidelines regarding the handling of biological material. Discard used consumables according to the safety guidelines of your institution or Iocal regulatory authority. CAUTION To minimize the danger when working with hazardous materials: » » »

avoid direct contact with chemicals and biological samples. always wear protective gear (safety glasses, gloves, protective clothing) when handling chemicals and/or biological samples. check regularly for possible chemical leaks.

In case of any liquid discharge, follow the cleaning instructions recommended in the material safety data sheets. Adhere to local or national guidelines when handling, storing, or disposing of chemicals and biological samples. Discard used consumables according to local safety guidelines or instructions of your local regulatory authority. NOTE the safety data sheets (MSDS) for the Unyvero Cartridges, Unyvero Sample Tubes and Unyvero Sample Tube Caps, Unyvero Sample Pre-Treatment Tool are available upon request from Curetis or your local contact.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

16 3.1 Overview The Unyvero System includes the following components: » » » » »

Unyvero Lysator Unyvero Cockpit Unyvero Analyzer Unyvero OS Software and Unyvero Plug-In Unyvero Sample Tube Holder

Instruments and Software

3

1

Fig. 1 Unyvero System

2

The Unyvero Lysator (1) lyses the samples. Based on newly developed technologies, the lysator is able to process a wide range of clinical sample types using a standardized protocol. The Unyvero A50 Analyzer (2) processes up to two Unyvero Cartridges in random access mode, and automatically performs DNA purification, specific amplification and detection. The Unyvero Cockpit (3) is equipped with a touchscreen and barcode reader, and connects the Unyvero Analyzer to the Unyvero Lysator. The Unyvero OS (software) and application-specific Unyvero Plug-Ins are part of the user interface that guides the user step by step through the process, and automatically generates and displays test results.

The consumables listed below are necessary to use the Unyvero System. They are available separately:

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

17 Consumables and Accessories The respective Unyvero Cartridge contains reagents for DNA isolation and purification, primers, hybridization buffers, wash buffers, and oligonucleotides for detection.

The Unyvero T1 Sample Tube contains glass beads and buffers to lyse bacteria and liquefy the sample in the Unyvero Lysator. The Unyvero T1 Sample Tube Cap seals the Unyvero Sample Tube. It contains proteinase K and a synthetic control gene for an integrated process monitoring. The Unyvero B1 Sample Tube contains glass beads and buffers to lyse bacteria and liquefy the sample in the Unyvero Lysator. The Unyvero B1 Sample Tube Cap seals the Unyvero B1 Sample Tube; and it contains proteinase K as well as a synthetic control gene for process monitoring. The Unyvero M1 Master Mix Tube is filled with reagents for DNA amplification. The Unyvero Sample Tube Holder holds the Unyvero Sample Tube securely while the patient material is transferred into the Unyvero Sample Tube (accessory supplied with the Unyvero System). NOTE The application-specific Unyvero Cartridges need specific Unyvero Sample Tubes and Caps, sample transfer, or pre-treatment tools, respectively. NOTE The indication-specific applications of the Unyvero System are described in the respective Unyvero Application manuals.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

18 3.2 Unyvero L4 Lysator The Unyvero Lysator can process all patient sample types approved for the respective application.

2

2 33

The user transfers the patient sample into the Unyvero Sample Tube that is already filled with the reagents necessary for sample lysis. The Unyvero Sample Tube is then closed with the Unyvero Sample Tube Cap and placed in the sample opening of the Unyvero Lysator.

11 Fig. 2 Opened Unyvero Lysator L4 1 Display 2 Cover 3 Sample opening

3

2

1

Fig. 3 Rear view of the Unyvero Lysator L4 1 LAN connection 2 On/off switch 3 Power chord connection

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

19 3.3 Unyvero Cartridge The Unyvero Cartridge (Fig. 4) integrates all relevant analysis steps:

1

2

Fig. 4 Unyvero Cartridge

1 Unyvero Sample Tube slot 2 Unyvero Master Mix Tube slot

DNA isolation

Multiplex endpoint PCR

DNA detection by hybridization on membrane arrays The Unyvero Cartridge is equipped with integrated reagent containers, a DNA purification column, eight separate PCR chambers, and a corresponding number of arrays. The cartridge contains buffers for DNA purification, reagents, and fluorescence-labeled primers for PCR amplification, and probes for array hybridization.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

20 The Unyvero Cartridge is assembled by inserting the Unyvero Sample Tube containing the lysed sample, and by inserting the Unyvero Master Mix Tube. Once assembled, the cartridge is physically closed, minimizing the risk of contamination. An internal control (a synthetic gene without any significant similarity to known sequences) is included in the cartridge to verify DNA purification, PCR and array hybridization for each measurement. This gene is amplified in each of the eight PCR chambers and hybridized on each array. Descriptions of the Unyvero Cartridges with their specific applications can be found in the respective application manuals.

3.4 Unyvero A50 Analyzer The Unyvero Analyzer consists of mechanical, electronic, and optical elements to perform all sample preparation and analysis steps of the cartridge. 1

2

Every Unyvero Analyzer has two cartridge slots that allow processing of Unyvero Cartridges completely independent of each other. Up to eight Unyvero Analyzers can be connected to a Unyvero Cockpit to increase output.

3

4 Fig. 5 Unyvero front view of the Unyvero A50 Analyzer

The Unyvero Analyzer does neither contain reagents nor waste, nor is there any exchange of chemicals between analyzer and cartridge. All necessary reagents are contained in the single-use cartridge. They are removed and discarded with the cartridge after completion of the measurement.

1 Left-hand slot 2 Display 3 Right-hand slot 4 On/off switch

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

21

1

2

1 Power cord connection 2 LAN cord connection

Fig. 6 Rear view of the Unyvero Analyzer

3.5 Unyvero C8 Cockpit The Unyvero Cockpit, together with the Unyvero Operating Software, features a touchscreen monitor with a user interface that guides the user through the work flow step by step. The Unyvero Cockpit has an integrated barcode reader that allows fast, automated import of sample ID barcode information. Expiration dates and lot numbers are recorded in the same way. The software allows results to be automatically generated, stored, and displayed.

1 2

Fig. 7

Unyvero C8 Cockpit

1

3

2

1 Touchscreen monitor 2 Barcode reader

4 Fig. 8 Rear view of the Unyvero Cockpit 1 Power switch 2 LAN cable connections for analyzers and lysators 3 USB ports 4 LAN connection for optimal network connection

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

22 3.6 Symbols Used Product number

Manufacturer

In-vitro diagnostic product

Dangerous electrical voltage warning

CE marking

Device complies with UL and CSA certified safety standards

Serial number

Do not dispose of in household waste

3.7 Analysis Principle The Unyvero Application automates and integrates DNA extraction and purification, eight parallel multiplex endpoint PCR reactions, and the qualitative detection of amplicons using hybridization on arrays in a single-use cartridge. » The sample is transferred to the Unyvero Sample Tube, sealed with the Unyvero Sample Tube Cap, and lysed in the Unyvero Lysator. » The Unyvero Sample Tube and the Unyvero Master Mix Tube are then inserted into the cartridge. » The Unyvero Cartridge is inserted into the Unyvero Analyzer, which processes the cartridge fully automated. The software guides the user through the entire process. A barcode reader allows the input of sample data and consumables. The software checks the expiration dates of the consumables and records them together with the lot number.

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

23 3.8 Unyvero Operating Software (OS) The Unyvero software installed in the Unyvero Cockpit generates the user interface that guides the user through the process step by step, and displays the test results.

1 2

Fig. 9 shows the Active Tests overview screen of the Unyvero Operating Software. Each bar symbolizes one active measurement. The color indicates the measurement status. 3

Bars are opened by tapping on them to display additional test information. The type of displayed information depends on the current status of the selected test. Gray bars indicate lyses in progress, or those that were completed. Purple bars represent analyses in progress. Completed tests are shown in blue. Test results are displayed when tapping on a blue bar. Unfinished tests that were either terminated by the user, or not completed due to a technical problem, are shown in orange. Fig. 9 The Unyvero OS Software Active Tests overview screen

Installation and set-up of the Unyvero System are 1 System status lights described in section 4. 2 Headline bar 3 Test bars 4 Function keys

© Curetis GmbH, 2017

Unyvero System Manual

Item No. 00117 Rev. 6.0

4