Dr Steve Green Origin Fertility Belfast, Northern Ireland

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2 Using the Integra 3 system we have seen a huge 20% increase in positive pregnancy outcomes after ICSI and embryo quality is consistently good. The improved temperature control over the objective during the ICSI procedure, as a result of the Thermosafe system, is a significant factor. Dr Steve Green Origin Fertility Belfast, Northern Ireland 1

3 INTEGRA 3 The World s Most Advanced Micromanipulation System NO COLD SPOTS Thermosafe maintains sample temperature with a gentle stream of warm air under the Petri dish ACCURATE New extra-fine mechanisms for smooth and precise movement of the stage and micropipettes SUPER-FAST Improved rapid micropipette set-up with one-step angle adjustment 2

4 INTEGRA 3 FEATURING THERMOSAFE FEATURING THERMOSAFE The new Integra 3 features the revolutionary Thermosafe which, by passing a gentle stream of air under the Petri dish, maintains sample temperature across the dish. A 3.5 inch colour touch screen display allows you to check and control temperature and track procedure time. The thermal images below, taken with a 40x objective in place on an inverted microscope, display the cooling effect of the objective in the centre of the dish with and without Thermosafe. Dish surface when placed on heated metal plate without Thermosafe Dish surface when placed on market leading glass ITO without Thermosafe Dish surface when placed on heated metal plate with Thermosafe Put simply, Thermosafe is an integral heating system that helps to keep samples at the optimum temperature. The result is no more cold spots, no more hot spots or ambiguity. 3

5 PRACTICAL Every detail of the Integra 3 is geared towards one goal to ensure you create the best possible conditions for ICSI and sample manipulation TEMPERATURE CONTROL Advanced temperature control in comparison with a glass ITO and metal plate without Thermosafe EASY TO USE Simple touch screen controls for adjusting stage temperature Uniform dish temperature No hot spots, no cold spots. WITH THERMOSAFE RI heated metal insert with Thermosafe air heating system Thermosafe air heating system Thermosafe prevents the objective from cooling the dish Heated metal insert 4

6 INTEGRA 3 FEATURING THERMOSAFE We recognise that temperature and time are critical within an ART lab. Integra 3 is ultraresponsive and effortlessly smooth, so it s quick and easy to use, thanks to RI s advanced mechanical design. You can change micropipettes in seconds, which can transform the efficiency of your lab overnight. We have increased the size of the integrated heated stage by 40% but kept the footprint to a minimum to keep your work area uncluttered. We have added a whole spectrum of other functions and features that make the Integra 3 the most intuitive and ergonomic mechanical micromanipulation system on the market. PRECISE & INTUITIVE CONTROL When you perform ART micromanipulation procedures, accuracy is paramount. Integra 3 offers the finest possible movement of the XY stage and fine and coarse levers as well as a choice of oil or air syringes for the control of specimens. SYRINGES The Integra 3 includes two of our SAS air syringes as standard. These syringes offer superb control and eliminate the need for oil. Also available is the SAS-SE for superfine air control, or our SOS oil syringe with a quick fill feature for minimum setup time. RI VIEWER SOFTWARE You can use the Integra 3 without a computer or camera. However, if you connect it to a computer, we can supply RI Viewer software. With RI Viewer you can use the shortcut keys. Enjoy sharp full screen imaging from the microscope, with digital magnification and a modern, clean user interface. It also offers line measurement tools and a built-in simulator for training and demonstration purposes. RI Viewer also allows you to synchronise with Saturn Laser and IMSI systems. MOTION-TRIGGERED LIGHT SHORTCUTS SAFE 5 A motion triggered light illuminates under the stage as soon as it detects your hand, to help you see when changing objectives If you need to keep track of samples or procedures, just hit the shortcut buttons to film or photograph any stage of the process. There is a counter button and an on-screen stopwatch as well Stage temperature control status indicator light and alarm monitors every second of the process. A log is kept of every alarm triggered

7 By far the best new feature is the warm air flow through the central plate which means your dish can maintain the correct temperature throughout the procedure. The egg counter feature has also been a blessing in large cases. Sophie Bird Guy s and St Thomas, UK 6

8 INTEGRA 3 FEATURING THERMOSAFE GREAT BRITISH QUALITY The Integra 3 is built at our high-tech factory in the South West of England. We have made thousands of micromanipulators since the early sixties, each one assembled under the diligent eyes of the designers who developed them. Our commitment to quality, durability and reliability has been there since day one. This is why our Integra has proven to be the micromanipulator of choice for ART clinics worldwide. 7

9 MICROSCOPE COMPATIBILITY TMD, An air warming system improves temperature stability during gamete and embryo micromanipulation procedures. 1 Nikon Diaphot 200/300, TE200/300, TE2000, Ti Stacy Wheat Cambridge IVF, UK Leica DMIRB, DMI3000B/4000B/6000B, DM IL, DMi8 1 Wheat, S Can temperature stability be improved during micromanipulation procedures by introducing a novel air warming system? Cambridge IVF, Cambridge - available on request COLOUR TOUCH SCREEN INTEGRATED Olympus IMT2, IX50/70, IX51/71/81, IX53/73/ inch touch screen display showing temperature, stopwatch and counter. The electronic height indicators track the vertical position of the toolholders Large built-in mechanical XY stage plus temperature controllers with easy access buttons and touch screen Zeiss Axiovert 40/100/200, Axio Observer, Axio Vert.A1 8

10 RI IMSI The RI IMSI system allows morphological screening of sperm cells at very high magnification and in real time. Studies suggest that this can lead to higher pregnancy rates 1,2,3 9

11 The RI IMSI system with the RI Viewer software allows us to visualise individual sperm in sufficient detail to assess their heads for the presence or absence of nuclear vacuolation. The system has allowed us to offer another effective treatment option to our patients and we are very happy with the treatment results we have achieved from our IMSI treatment cycles to date. Stephen Harbottle, Cambridge IVF CLINICAL IMSI Speed, affordability and compatibility are important to you. So with this in mind RI has developed a software and camera package for Intracytoplasmic Morphologically-selected Sperm Injection (IMSI), widening the scope of procedures you can perform on your micromanipulator. Marrying your microscope provider s recommended objective and condenser combination and RI s highsensitivity camera, medical grade monitor and versatile imaging software, you can now achieve outstanding image quality for the screening of sperm cells. Teamed with RI s Integra 3 micromanipulator you have the perfect tool to ensure the fast and efficient use of the technique. The camera s large sensor has high-sensitivity pixels for bright, high contrast images. The pixel count is a perfect match for the resolution of your optics, and allows smooth video at 15 frames per second. RI IMSI is supplied with the easy to use RI Viewer software the only application you need for ICSI and IMSI. Capture, record, annotate and measure, with intuitive zoom and pan on screen. MICROSCOPE COMPATIBILITY TMD, TI, Nikon Diaphot 200/300, TE200/300, TE2000, DMIRB, DM IL, Leica DMI3000B/4000B/6000B, DMi8 Olympus IMT2, IX50/70, IX51/71/81, IX53/73/83 1 Bartoov, B et al, Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome, Journal of Andrology, Vol. 23, No. 1, January/ February Cassuto, N et al, A new real-time morphology classification for human spermatozoa: a link for fertilization and improved embryo quality, Fertility and Sterility, Vol. 92, No. 5, November Kim, H.J. et al., Comparison between intracytoplasmic sperm injection and intracytoplasmic morphologically selected sperm injection in oligo-asthenoteratozoospermia patients. Clinical and experimental reproductive medicine, 41(1), pp Available at: pmc /?tool=pmcentrez Zeiss Axiovert 40/100/200, Axio Observer, AxioVert.A1 10

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13 SATURN 5 Fixed and Directional Laser System PRECISE Sub-micron accuracy and unique computer controlled laser with guaranteed laser alignment RAPID Faster than ever directional laser increases functionality and decreases procedure times CURVED BIOPSY MODE Biopsy Mode allows accurate laser drilling along a drawn straight or curved line 12

14 SATURN 5 FASTER BIOPSIES The Saturn 5 Biopsy Mode helps you to significantly improve biopsy methods, potentially reducing procedure time, lowering the incidence of blastocyst collapse and eliminating the need to mechanically tear off cells 1. Using Biopsy Mode, you can draw a straight or curved line along the sample, select the number and size of holes, then simply fire. The laser will ablate exactly along the chosen path, meaning you no longer need to move the holding pipette at all. It is that easy. ALWAYS SPOT-ON As the Saturn 5 pilot laser travels down the same fibre optic path as the ablation laser, it guarantees consistent positioning. You can calibrate and verify hole size and firing position with sub-micron accuracy simply and quickly, leaving more time for your procedures. COMMITMENT TO EMBRYO SAFETY Multiple safety features ensure the Saturn laser is the safest laser on the market. To keep your embryos safe, features include the Exclusion Zone 2 which can be set according to distance. By employing a higher laser power, the Saturn Laser applies less total energy to make a specified hole size, in comparison to lower power laser systems 3. IMAGE GALLERY RI Viewer Image Gallery provides centralised access to all images and videos taken of your samples. Files can be assigned to patient folders with ease, notes added or images printed. It simplifies your workflow and keeps you organised. INTUITIVE SOFTWARE AS STANDARD In addition to its intuitive use and safety assurances, the new Saturn 5 features RI Viewer software. The software offers uncluttered full screen imaging from the microscope, digital magnification and a modern, clean user interface. RI Viewer also offers a recording function, line measurement tools which are visible on-screen and are printable, plus a built-in laser simulator for training and demonstration purposes. RI Viewer supports a range of languages. 1,2,3 Please see page 15 for references. EASY TO USE SAFEST POWER VERSATILE 13 Intuitive RI Viewer software with streamlined user interface. An optional programmable foot pedal controls software and laser functions Lowest laser pulse times for minimal energy near critical cells. Exclusion Zone feature ensures cell safety Compatible with all popular brands of micromanipulators and inverted microscopes, available with a choice of 20x and 40x objectives

15 The moveable Saturn Laser means I can ablate the zona exactly where I want to, without having to move the embryo. Samantha Knight SPIRE London Fertility Clinic, UK ENERGY DELIVERED VS HOLE DIAMETER 3 USING SATURN LASER (400mW) 175mW 300mW Energy Delivered (µj) 400mW Diameter of Hole Produced (µm) 14

16 SATURN 5 APPLICATIONS 4,5 For blastocyst/trophectoderm biopsy, the Saturn 5 Active is unparalleled in its ease of use. The directional laser allows you to make multiple ablations across the trophectoderm cells without needing to move the blastocyst. This offers superb accuracy, safety and incredible speed. For blastomere biopsy, polar body biopsy and blastocyst collapsing (for vitrification), the Saturn 5 Active Directional Laser allows the embryo to stay in the desired position and focus, so that ablations can be made wherever required without additional manipulation. Our Biopsy Mode also allows safe drilling along a predetermined line. The Saturn 5 Laser has really improved and sped up my procedures. The Saturn 5 Active Laser is very impressive as it gives you a lot of freedom in how you do the procedures, the software is very easy to use, very comprehensive and the biopsy mode helps me process the cells for PGD. Dr Melihan Bechir Fertilia MedLife, Romania For assisted hatching, the moveable laser means accurate ablations can be made without the need to hold the embryo, avoiding additional consumable costs. 15 You will find these procedures can be performed quickly and accurately using the Saturn 5 Active, unlike fixed lasers. 1 Lloyd S, Doshi A, Harper J, Application note. A new method of biopsying TE cells using the latest Saturn 5 Active Laser System offers several potential ways to improve your procedures - Available on request. 2 Chatzimeletiou, K., Picton, H.M & Handyside, A.H., Use of non-contact, infrared laser for zona drilling of mouse embryos: assessment of immediate effects on blastomere viability. Reproductive Biomedicine Online, 2(3), p.178. Available at: 3 RI White Paper. A comparison of different power levels used by laser systems in the IVF laboratory Available upon request. 4 The applicability of procedures is dependent on the regulations of the country into which the device is sold. 5 In the USA, FDA cleared for clinical use for embryo biopsy, trophectoderm biopsy, blastocyst collapsing and Laser Assisted Hatching (LAH).

17 MICROSCOPE COMPATIBILITY TMD, Ti, Nikon Diaphot 200/300, TE200/300, TE2000, DMIRB, DM IL, Leica DMI3000B/4000B/6000B, DMi8 Olympus Zeiss IMT2, IX50/70, IX51/71/81, IX53/73/83 Axiovert 40/100/200, Axio Observer CLASS I LASER ESSENTIAL BIOPSY TOOL TOTAL CONTROL Saturn 5 Laser Systems are Class I laser products as defined by international laser safety standards. They are CE marked and FDA cleared 5 The Saturn 5 Biopsy Mode is quickly proving to be an essential tool in the practise of biopsying across the world Preset options allow Lab Managers to predefine their preferred laser setting for each procedure helping to speed up and standardise processes 16

18 SYRINGES SAS - SCREW-ACTUATED AIR SYRINGE be positioned next to the control lever of a micromanipulator, allowing single-handed operation of both instruments. SOS - SCREW-ACTUATED OIL SYRINGE For air-assisted micro-injection and microaspiration, the SAS syringe applies suction or pressure to a micropipette. It can generate high pressure when required, yet is sensitive enough to balance the capillary action of media in a micropipette and to precisely position a sample. The SAS is typically connected by polythene tubing to a micropipette holder mounted on a micromanipulator. Pressure or suction is applied by turning the top part of the SAS. A heavy circular base gives great stability. Its compact dimensions enable the SAS to A convenient button on the top of the syringe releases the pressure quickly in the event that the sample is moving too fast or too much positive pressure has been applied. SAS-SE - SCREW-ACTUATED AIR SYRINGE SPECIAL EDITION The SAS-SE offers a more refined, super-smooth control that responds precisely to the slightest movement. It has superb pressure control and is ideal for manual microinjection. The SOS oil syringe provides outstanding control and precision through a tightly sealed oil system. It is specially designed for micro-injection of spermatozoa and the holding, extraction and transfer of cells. A small, complete unit, the SOS incorporates a sturdy non-slip base. Its ergonomic design enables it to be easily operated and positioned next to the control lever of a micromanipulator to facilitate single-handed operation of both instruments. An easy filling system enables an ultra quick and airfree refill or top up of the syringe. SAS SOS SAS-SE 17 High pressure when required, yet is sensitive enough to balance the capillary action of media in a micropipette and to precisely position a sample Outstanding control and precision through a tightly sealed oil system Refined, super-smooth control that responds precisely to the slightest movement.

19 The Integra 3 includes two of our SAS air syringes as standard. Also compatible is the SAS-SE for superfine air control or our SOS oil syringe. All three syringes are compatible with other micromanipulation systems. Adaptors can be supplied where necessary. DESCRIPTION SAS SAS-SE SOS Piston Stroke 23mm 30mm 50mm Max Displaced Volume Volume Displaced Per Turn 18.5ml* 24ml* 830µl 1.6ml* 1.6ml* 8.3µl Weight 1.4kg 1.7kg 1.5kg Overall Dimensions 125mm diameter x 95mm high 125mm diameter x 120mm high 260 x 135 x 80mm *At atmospheric pressure only. Due to pressure differences, the actual volume displaced in the pipette is considerably smaller, and will vary according to the geometry of the micropipette and the viscosity of the media used. 18

20 MKTG-BR /06/2016. All information correct at the time of print. Specifications are subject to change without notice or obligation on the part of the manufacturer.