Introduction to picoSpin for Service and Support Engineers

Outline Key learning Overview Product description Technology Marketing product brief Service support roles Technical Support Warranty Front panel Rear panel Specifications Inside the box Capillary cartridge Inside the cartridge Cartridge, magnet, preamplifier Software Website resources FAQ’s

Key Learning The primary goal in this presentation is to provide field service engineers an introduction to the picoSpin product, including: Product overview: what is a picoSpin? Field service support: is it serviceable in the field? who installs it? Repair: if it breaks who fixes it and where? Warranty: how long is the warranty period? Technical support contact: who do I contact if a customer has questions?

Overview The picoSpin is an NMR (Nuclear Magnetic Resonance) product that was acquired by Thermo Fisher Scientific in December of 2012. In 2010, picoSpin introduced the picoSpin 45, which offered the capabilities of larger spectrometers in a much more affordable, shoebox-sized unit. Headquartered in Boulder, Colorado, the picoSpin product line is part of the Molecular business unit within the Chemical Analysis Division (CAD). As of July 2013, the production of the picoSpin 45 system is being performed in Madison, WI. In August, 2013 the picoSpin 80 was introduced. The picoSpin 45 and 80 systems are simple enough to be installed by customers. Installation by field service engineers is not necessary please refer to slide 8 for additional information

Product Description picoSpin is the world first miniature NMR spectrometer. The picoSpin 45 NMR spectrometer is a complete 45 MHz pulsed Fourier-transform liquid-phase proton NMR spectrometer in a shoebox-sized package. To date, the picoSpin 80 has the highest magnetic field strength (2 Tesla) and highest resolution (20 ppb) of all known bench-top NMR spectrometers on the market. It provides an 82MHz resonance frequency for 1H detection and a capillary injection port, obviating the need for dedicated NMR tubes. Deuterated solvents are not required (although can be optionally used to avoid large protic solvent signals); field drift is compensated for automatically in software. Both the picoSpin 45 and 80 includes a capillary cartridge, a permanent magnet with temperature controller and shim system, radiofrequency transmitter and receiver, digital data acquisition and signal processing, a programmable pulse sequencer, and a web browser user interface. The picoSpin software system is hosted on the spectrometer and is ready to be used once the spectrometer is turned on and connected to any computer.

Technology Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei. It determines the physical and chemical properties of atoms or the molecules in which they are contained. It relies on the phenomenon of nuclear magnetic resonance and can provide detailed information about the structure, dynamics, reaction state, and chemical environment of molecules. Most frequently, NMR spectroscopy is used by chemists and biochemists to investigate the properties of organic molecules, although it is applicable to any kind of sample that contains nuclei possessing spin. Suitable samples range from small compounds analyzed with 1-dimensional proton or carbon-13 NMR spectroscopy to large proteins or nucleic acids using 3 or 4-dimensional techniques. The impact of NMR spectroscopy on the sciences has been substantial because of the range of information and the diversity of samples, including solutions and solids.

Copyright © 1997-2011 J.P. Hornak. All Rights Reserved. Technology The Basics of NMR, by Joseph P. Hornak, Ph.D. Almost every section of this excellent text will be helpful to users of the picoSpin 45. The only sections that are not directly relevant are these: carbon-13, superconducting magnets, solid state, microscopy, and field cycling. Joseph P. Hornak, Ph.D. Professor of Chemistry, Materials Science & Engineering, and Imaging Science Director, Magnetic Resonance Laboratory Rochester Institute of Technology, Rochester, NY Copyright © 1997-2011 J.P. Hornak. All Rights Reserved.

Marketing Product Brief Message The Thermo Scientific picoSpin™ Proton NMR Spectrometer is the first fully featured bench-top NMR spectrometer, offering smaller laboratories a solution to the limited accessibility and prohibitive cost of traditional NMR instruments. Priced affordably for educators yet robust enough to meet the standards of industrial quality control and organic chemistry laboratories, the picoSpin spectrometer brings NMR capabilities to more analysts, chemists and students alike. It processes liquid samples as small as 20 microliters, producing data in the industry standard JCAMP-DX format for easy analysis. Because the picoSpin spectrometer weighs less than 5 kilograms (picoSpin 45) and 20 kilograms (picoSpin 80) and is easy to install, multiple laboratories can share a single instrument. The spectrometer is easier to maintain - its fluid capillary is contained within a cartridge, so it is easily replaced by users if blocked or contaminated, and its temperature-controlled permanent magnet does not require liquid cryogens, reducing the need for consumables. The low cost, easy to operate picoSpin spectrometer is ideal for small- to mid-sized academic and industrial laboratories, especially those focused on polymers, chemicals and pharmaceuticals.

Service Support Roles – Field Service The picoSpin 45 and 80 is simple enough to be installed by customers and thus field service installation is not necessary. The only consumable part on the picoSpin is a capillary cartridge which can be replaced by the customer without the need of field service. The picoSpin instrument is not repairable in the field. If there are issues with a picoSpin in the field, it will need to be returned to the factory depot center (Madison, WI) to be repaired. Technical support needs to be contacted prior to returning a picoSpin 45 and 80 to the factory depot center. Please refer customers to technical support representatives (see next two slides) if they have technical questions on the picoSpin instruments.

Service Support Roles – Technical Support International Technical Support The Product Support Engineering (PSE) group provides front-line email and telephone support for Field Service Engineers and Channel partners outside of US and Canada. International customers, channel distributors and direct Thermo Fisher Field Service Engineers will be supported through Advocate, the PSE email customer support system. Emails sent to International support inbox will be responded to by PSE’s monitoring the Advocate email handling system. The PSE goal is to respond within 24 hours with a complete and accurate response. Email: support.madison@thermofisher.com Phone: 1-608-273-5017

Service Support Roles – Technical Support Domestic Technical Support Technical support for domestic U.S. and Canadian customers is provided by the ULS Technical Services Group. Technical services will give priority support to domestic warranty and service contract customers. Demand billable calls will be routed to the end of the call-waiting cue. The target is to respond to all warranty and service contract customer calls within two hours. Email: us.customer-support.analyze@thermofisher.com Phone: 1-800-532-4752

Warranty Thermo Scientific warrants that each product we sell is free from defects in labor and materials and shall conform to its product specifications as defined in the product user documentation. The standard warranty period is 12 months from the date that the installation was accepted and signed off by the customer or 14 months from the date of shipment after the system ships from the factory or whichever comes first. There are no parts in the picoSpin 45 or 80 that have an extended warranty past the original 12-14 month main system warranty.

picoSpin 45 and 80 Spectrometer Front Panel LCD Display Sample inlet port Replaceable Cartridge Note: picoSpin 80 front panel is similar (see slide 15) 13

picoSpin 45 and 80 Spectrometer Back Panel Cooling Fan ON/OFF Switch Power Connection +12 V: 110-240 VAC Cat-5 Ethernet Connection RS-232 Accessory Port 14

picoSpin 45 Product Features and Specs 45 MHz Pulsed FT NMR spectrometer Proton NMR of liquids; 19F version Better than 40 ppb typical resolution Single-shot SNR for water > 1000 10.5 lbs total weight; 5” x 8” x 10” Replaceable 400 µm ID capillary cartridge 30 µL sample volume Controlled by any web browser No cryogens, no compressed gas, etc. No special environment All solid-state, no moving parts Optional 12 month license to Mnova

picoSpin 80 Product Features and Specs 82 MHz Pulsed FT NMR spectrometer 1H instrument 20 ppb resolution 43 lbs total weight 17” x 14” x 10” Replaceable 400 µm ID capillary cartridge 40 µL sample volume No cryogens, no compressed gases needed No special environment Solid-state technology, no moving parts Ethernet interface; controlled by web browser Optional 12 month license to Mnova

Inside the Box picoSpin 45 and 80 Embedded web server **No field replaceable parts **Depot repair ONLY! Data converters, DSP Pulse sequencer Rx and Tx amplifiers Shim coil controller RF preamplifiers Permanent magnet Magnet temperature controller Fluid cartridge and sub-panel

Capillary Cartridge picoSpin 45 Flange Sub-panel 30 µL sample volume Replaceable 400 µm ID capillary cartridge Flange Sub-panel

Inside the Cartridge Tx/Rx Microcoil 0.3 mm ID quartz capillary PTFE transition Cartridge is customer replaceable

Capillary Cartridge, Magnet, Pre-amplifier

Software picoSpin software is controlled by any web browser. Firefox browser is recommended.

Website Resources www.picospin.com www.thermoscientific.com PRODUCT SUPPORT WEBSITE (24/7) http://pghcr-pse-01/ (Thermo Scientific Employees) http://madisonsupport.thermofisher.com  (Approved Distributors)

FAQ’s General Questions Is the Thermo Scientific™ picoSpin™ 45 NMR spectrometer really the world’s first miniature NMR spectrometer? Haven’t desktop NMR machines been around for years? In a proton NMR spectrum, lines are typically separated by a few parts per million (ppm). To qualify as a true spectrometer, an NMR system must have resolution well below 1 ppm. The picoSpin 45’spicoSpin 45’s resolution is better than 0.04 ppm, or 40 ppb (parts per billion). Before the picoSpin 45, all commercial miniature NMR machines had resolution that was too poor for them to qualify as spectrometers. They could be used to analyze NMR relaxation times, but they were not spectrometers in the sense usually meant in NMR. So yes, the picoSpin 45 really is the world’s first miniature NMR spectrometer.

FAQ’s General Questions How does it work? The picoSpin 45 is, in most respects, a conventional Fourier-transform proton NMR spectrometer. It has all of the usual NMR spectrometer components including a magnet, shim coils, programmable pulse sequencer, RF transmitter, solenoid RF coil, low-noise receiver and digital data acquisition system. What is different is just that everything is so small. Instead of a large and expensive superconducting magnet, we use a fist-sized room-temperature permanent magnet. The electronic circuits are all miniaturized using techniques similar to those used in cell phones. The sample fluid is confined to a small capillary with an inside diameter of about 0.4 mm.

FAQ’s General Questions How stable is the picoSpin 45? Can I use averaging to improve the signal-to-noise ratio? The system is stabilized by a magnet temperature controller and by software techniques. If the sample itself behaves in a time-independent way, any number of single scans can be averaged together to improve SNR. Can I look at flowing samples? Yes, but spectroscopic resolution will suffer unless the sample is stationary during the NMR data acquisition. For most applications, either the inlet port or the outlet port should be closed during data acquisition, and there should be a small fluid volume between the closed valve or plug and the port. Otherwise, thermal expansion of the fluid can cause flow.

FAQ’s General Questions Why does the picoSpin 45 have a capillary cartridge? For convenient replacement. When reasonable precautions are observed, problems with clogging and contamination of the capillary can be avoided. However, accidents do occur, and when they do, it is a great advantage to be able to replace the capillary in the field. Cartridge changes only take a few minutes. The unit should be reshimmed whenever the cartridge is changed.

FAQ’s Sample Handling for the 1/32-inch Fittings How do I inject a sample? The spectrometer has an inlet connector and an outlet connector on the front panel. The fluid path between them is a capillary with an ID of about 0.4 mm and a total volume of about 30 microliters. Samples are most often injected into the capillary using a syringe. Kits of parts and accessories for sample handling are available. What materials are in contact with the sample fluid? Our standard cartridges use microbore PTFE capillary and a short section of quartz glass capillary at the location of the RF coil. The inlet and outlet front panel fittings are stainless steel. The optional inlet filter has a PEEK body and stainless steel frit filter. PEEK ferrules are used to connect the microbore PTFE capillary to the front panel fittings. Contact us to discuss other materials for special applications. How do I remove a sample? Just flush the capillary with either a clean solvent or your next sample.

FAQ’s Chemical Applications What kind of samples can I measure? Any proton-containing liquid, not too viscous for injection into a 0.3 mm ID capillary, can be used. How long does it take to get a spectrum? This can vary widely. For a high-concentration sample of a simple molecule, you can get very useful information from a single scan acquired in less than a second. One the other hand, if you are looking for a low SNR line, and your sample has a long T1 relaxation time, you may want to collect data for many minutes or even several hours. See previous question to learn how to estimate the SNR. Do I need to use deuterated solvents? Not in most cases. Deuterium is not used by the picoSpin 45 to provide a lock signal, and receiver saturation is also not a problem, even with a pure water sample. You might want to use a deuterated solvent if you find that a solvent proton signal overlaps strongly with an important solute signal.

FAQ’s Chemical Applications Will the signal I am looking for be strong enough to see? Good question! It is always a good idea to estimate the signal-to-noise ratio (SNR) before you get started with unfamiliar samples. The exact SNR depends on many things, including the magnet shim and the way data is recorded and analyzed. However, you can usually make an adequate estimate like this: The picoSpin 45 single-scan SNR for pure water is about 500, and the concentration of water molecules in pure water is 55 moles/liter. Since the SNR is directly proportional to concentration, you can scale from this case to estimate your SNR. You should also include a factor for the “weight” of the line relative to the weight of the water line. The weight is the number of protons per molecule contributing to the line times the line’s normalized intensity within a multiplet if it is not a singlet. (For example, a water singlet has a weight of 2, a CH3 singlet has a weight of 3 and one line in a CH3 doublet has a weight of 1.5.)

FAQ’s Chemical Applications Let’s say your molecule has a concentration of 0.55 moles/liter, and you want to estimate the SNR of one line in a CH3 doublet. That will be 500*(0.55/55)*(1.5/2) = 3.75. You can increase the single-scan SNR by averaging many scans. The SNR increases as the square root of the number of scans – so if you average 100 scans, you can enhance the SNR by a factor of 10. (We use the spectroscopist’s definition of SNR, which is the peak height of the line divided by the RMS of the baseline.) Can I detect other nuclei besides hydrogen? A special version of the picoSpin 45 is available for fluorine. The electronics can be adapted for any frequency, but the SNR will not be adequate for most applications with nuclei other than hydrogen and fluorine. Carbon-13 satellites can be seen on proton spectra in favorable cases.

FAQ’s Installation Where can I install a picoSpin spectrometer? There are no special facilities or environmental requirements. You can place a picoSpin spectrometer in any indoor location where a person would be comfortable. AC magnetic fields generated by nearby utility power that are stronger than 1 mgauss amplitude will cause small side-bands to appear on spectra. In unusual cases where this is a problem, the unit can be oriented so that the AC field vector is perpendicular to the magnet’s field. Will a picoSpin technician install the unit in my lab? Set up and operation of the picoSpin 45 is far simpler than for conventional NMR spectrometers. In most cases, customers with only a little or no knowledge of NMR have no problem installing the picoSpin 45 system.

FAQ’s Data Analysis How do I analyze my data? The picoSpin 45 generates data in the industry-standard JCAMP-DX format. Any NMR data analysis package that can read this format may be used to analyze your data. A one-year license to M nova™ NMR software from Mestrelab Research is included with each picoSpin spectrometer. Trademark Information Mnova is a trademark of Mestrelab Research S.L. All other trademarks are the property of Thermo Fisher Scientific Inc. and its subsidiaries.