NMR Facility (Peter Schmieder, Hartmut Oschkinat)

The NMR-facility at the FMP in Berlin-Buch - a history

The NMR-facility at the FMP in Berlin-Friedrichsfelde was established in 1990 with the purchase of a 200 MHz Varian spectrometer. It was capable of running 1D and 2D measurements with protons and carbon-13 as a nucleus and was used for routine measurements. More sophisticated spectra, especially of the peptide chemistry department, were run externally, e.g. in Frankfurt (Prof. Rüterjans) or Munich (Prof. Kessler).

To establish NMR spectroscopy at the FMP as a method for structure determination of biopolymers, the department of NMR-supported structural biology was created in 1995, with Hartmut Oschkinat as the head of the department. At the end of that year, a 600 MHz Bruker spectrometer was installed at the FMP on the campus in Friedrichsfelde.

In the next year (1996) the purchase of a 750 MHz-spectrometer was possible. There was, however, no suitable place for the installation of such a spectrometer in Friedrichsfelde and a temporary housing on the research campus in Berlin-Buch - close to the site where the new FMP building was to be erected - was choosen.

After the preparation of the temporary housing the DMX 750 was installed at the end of 1996 - with some minor problems.....

In subsequent years two major developments lead to an extension of the facility. The department was planning to establish solid state NMR as a method to determine structures of membrane proteins. This made the acquisition of a dedicated solid state machine (400 MHz WB) necessary, in addition the 750 was equipped with the possibility to run solid state spectra. The FMP also took part in the BMBF-project leading to the Berlin protein structure factory (PSF). The BMBF-grant enabled the department to buy two 600 MHz spectrometers for high throughput structure determination in 1999 and 2001. The increased number of spectrometers made a separate NMR building close to the new institute mandatory.

The construction of NMR-I started in 1998 and the building was designed to hold 5 spectrometers. It was opened in 1999 and the 600 MHz spectrometer of the PSF as well as the 400 MHz solid state spectrometer were installed that year.

When the temporary building of the 750 had to be removed during the construction of the new FMP main building, the 750 moved into the facility in summer 2000, the old 600 MHz spectrometer was moved from Friedrichsfelde to Buch shortly before the move of the FMP in the fall of 2000.

Meanwhile the 600 MHz spectrometer of the PSF had been equipped with a sample preparation robot to enable library screens using NMR spectroscopy. In addition, a cryogenic probe of the TXI type was added to the spectrometer to enable screens with a minimum amount of protein material and boost the structure determination projects.

In 2001 the order of a 900 MHz spectrometer was made possible by funds from the BMBF and the city of Berlin. A new NMR building was therefore necessary, it was planned together with the Max-Delbrück-Center, that was intending to establish a tomography group. The new building was designed to not only hold the 900 MHz spectrometer but to hold two more NMR spectrometers that were to be acquired with the extension of the NMR facility to an international NMR competence center.

In 2002 the successful work on solid state NMR created an increased need for measuring time on a dedicated solid state machine. The order of the second spectrometer of the PSF was therefore converted into a 600WB spectrometer in April. This type of spectrometer was clearly to big for the room in NMR-I and it was decided that it should be installed in NMR-II right away. The foundation of Combinature Biopharm AG, a small biotech company using NMR spectroscopy for the analysis of natural compounds and protein structure determination and screening, created the need for a properly equipped room to house another 600 MHz spectrometer for solution NMR. It was installed in NMR-I in Mai 2002 and subsequently equipped with a cryogenic probe of the TXI type in the summer of 2003.
Constructions of NMR-II were begun in the summer of 2002. The construction was completed in December 2002 and the 600WB magnet was brought into the building in January 2003 and installed until February 2003.

After several month of delay and waiting, the 900 MHz spectrometer was finally delivered in April 2004 and installed during the subsequent month until september including several quenches. Meanwhile the demand for highest sensitivity made the purchase of a cryogenic probe for the 750 MHz spectrometer necessary that was installed in October 2004. The probe was already of the new TCI type to enable the use of new carbon-detecting techniques.

After preliminary test at the 900 problems occurred cumulating in a quench in November 2004. It was decided that the magnet would need repair work that could not be performed on site and the magnet was retransferred to Karlsruhe. It returned already in December 2004 and was reinstalled over christmas. It was brought to field in February 2005 without problems and passed all tests for solution state and solid state NMR until march 2005.

In 2004, the chemistry department at the FMP was extended, which raised the demand for a dedicated NMR spectrometer to solely perform routine measurements. Since the original 200 MHz spectrometer had been retired with the move to Buch, a 300 MHz spectrometer was ordered together with a 700 MHz wide bore spectrometer. The latter was supposed to aleviated the pressure on solid state measurement time. While there was space for the 700 MHz spectrometer in NMR-II, the NMR facility had filled up with 8 spectrometers. The 300 MHz spectrometer was therefore installed in the basement of the main building in march 2005.

In the summer of 2005, the 700 MHz spectrometer finally arrived and was installed in NMR-II until the mid of September, lifting problems with the solid state measurment time. The two NMR buildings had thus filled up with 8 spectrometers, including the 300 MHz spectrometer the whole NMR facility contained 9 spectrometers availible to researches and also companies in the Berlin area and beyond.

In 2006, the new building for medical genomics was finished and the 300 MHz spectrometer moved from its preliminary site in the basement of the FMP to its new home in that building. To speed up things the magnet was left on field and moved on a special wagon all the way from the basement of the FMP to the fourth floor in the new building via two elevators. Measurements had thus only to be interupted for only 4 days.

In 2007, the hardware cabinet of the 750 MHz spectrometer was ten years old and outdated in several respects. A new hardware cabinet of AV-III type was therefore installed in Mai 2007, making the machine an up-to-date and, because of the TCI cryoprobe, extremely sensitive machine.
In addition, another solid state spectrometer was purchased, that was also intended to be the spectrometer where the DNP-technology was to be implemented. It was a 400 MHz wide bore spectrometer. Since the room situation had not changed in the two NMR buildings and since it was an ultrashield plus magnet, it could be installed in the basement of the main building close to the site were the 300 MHz machine had been. Installation took place in Mai 2007 and the machine was ready to go in June 2007.

In the fall of 2007 it became clear that two developments would make a further extension of the facility necessary. A group using in-cell-NMR spectroscopy was to be established, headed by Philip Selenko. It was clear that an additional spectrometer would be required to satisfy the need for solution-state measurement time. With respect to solid state NMR Bruker announced that a DNP gyrotron would be commercially availible in 2008 and the after the BMBF had agreed to provide funds for this additional piece of equipment the FMP decided to realise the addition as planned already when the second 400 WB was purchased. Earlier that year the Experimental and Clinical Research Center (ECRC) had been founded by the MDC and the Charitee. It would include a high-field MRI department and obtain a dedicated building for MRI. That made the part of NMR-II originally designed for a small MRI machine availible and the room was remodelled in 2008 to host the new 600 MHz spectrometer and one of 400 MHz spectrometer together with the gyrotron to do DNP experiments.

While waiting for the new 600 MHz spectrometer and the move of the 400 MHz spectrometer a rather unfortunate event took place in the facility. During the replacement of an UPS the old UPS got out of control and ended up at the magnet of the 750 MHz spectrometer, which had to be taken off field to remove the UPS and to check for damage. After a lengthy recharging process which was hindered by several adminstrative problems the spectrometer was operational after almost a year and is working reliably since then.

Once the remodelling of NMR-II was completed, it was time to fill the new rooms with NMR spectrometers. In October 2008 the new 600 arrived and was installed in one of the new rooms in NMR-II. The installation went smoothly and the machine was operational in November.

Immediately afterwards the move of 400 MHz machine took place. To set up an optimal environment for the DNP technique, the modern console that had arrived with the second 400 MHz spectrometer and had been installed in the basement of the main building was transfered to NMR-II. The magnet of the older 400 moved there as well while the old cabinet went to the basement resulting in the end in a swap of the magnet. Both 400 MHz spectrometers were quickly operational again and NMR-II waited for the arrival of the gyrotron.

The gyrotron arrived in January 2009 and was subsequently installed in NMR-II. The spectrometer was now operating with two magnets - connected by a microwave transmission line - and a solid state low-temparature probe allowing for experiments at nitrogen temperature.

NMR-II had originally been designed to be supplied with nitrogen from the tanks at NMR-I. With the extension of the building and the amount of nitrogen neccessary for the DNP technology that was not longer possible. The supply of nitrogen for NMR-II was reorganized by adding a larger tank to provide nitrogen gas and move an exisiting tank that had provided nitrogen for the building for medical genomics (TRH) in the vicinity of NMR-II. Both tanks were now providing liquid and gaseous nitrogen to NMR-II and the TRH.

In 2009 another magnetic resonance group also found a research environment at the FMP. Leif Schröder was planning to establish an imaging group at the FMP and consequently the 400 MHz spectrometer in the basement of the main building was equipped with the appropriate devices to perform those experiments. The installation took place at the end of 2009 and early in 2010. In the same year the DRX-cabinet of the second 600 MHz-spectrometer became increasingly unreliable and was replaced with a new AV-III cabinet. In addition, the cryoplattform of the same machine had to be replaced by a new device, which was done early in 2011. In parallel the magnet of the first 600 MHz spectrometer had reached the age of 15 years and was beginning to consume excessive amounts of liquid helium. Since this problem was not resolved by improving the vacuum of the magnet, it was taken off field, renovated and recharged in January, which was unfortunately not possible without a quench.

More changes in the facility were planned in that year: Since the DNP work showed that this technology was indeed very promising it seemed attractive to transfer it to higher field. The hope to use the same gyrotron and just doubeling the frequency therefore initiated plans for a wide-bore 800. To place the new magnet close to the gyrotron the room now occupied by the solution state 600 MHz spectrometer seemed the best choice. One of the 600 MHz spectrometers in NMR-I belonged to the company Evotec, which had taken it over from Combinature Biopharm after the purchase of that company by Merlion. Evotec was planning to concentrate its german business in Hamburg as much as possible and the spectrometer was therefore to move to a freshly prepared site, Evotecs Manfred Eigen Campus in Hamburg in the spring of 2012. This made the room availible for the 600 MHz spectrometer from NMR-II, bringing all dedicated solution state spectrometers together in one building. In addition, the hardware cabinet of the "old" 600 MHz spectrometer in NMR-I had now reached an age of 16 years. Even though it was still ticking like a swiss clock it was not capapble of running the newest software versions. It was therefore to be retired and replaced by a new Avance-III cabinet, together with a new broadband probe that would prepare the spectrometer for an anticipated increasing demand for routine spectroscopy after an expansion of the chemistry department of the FMP.

After repeated delays for the move of Evotecs spectrometer because of problems with the site in Hamburg, the move finally took place in march of 2012. The room was slightly modified and brushed up before the 600 MHz spectrometer moved from NMR-II to NMR-I. Given that the magnet was an "ultrashield plus" Bruker decided to do the move without uncharging the magnet. This secured some nerve-racking moments but in the end everything went well, sparing the facility the time consuming uncharging and charging. Simultaneously the new hardware cabinet arrived and so the June was filled with a double installation that was finished by the end of June.

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)

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