Ophelia: the fabulous story of the machine that changed mass spectrometry in Portugal

Like boats that cross rivers and oceans, mass spectrometers that carry human knowledge to the most elementary particles are also often named by those who use them. Ophelia brings a touch of Shakespearean inspiration and does not detract from the tradition. Judging by the records of the British manufacturer AEI, it is a worthy representative of the MS902 models, which guaranteed unprecedented measurement accuracy in the 1970s, but for different generations of researchers at the Faculty of Sciences of the University of Lisbon (Ciências ULisboa), it is much more than just four tons of metal. And that is why today it is part of the permanent exhibition at the National Museum of Natural History and Science (MUHNAC), as an example of a machine that made it possible to know what things are made of.

“It was for many years a great pedagogical and research tool. It has enormous historical value, because it completely changed the study of mass spectrometry that was done in Portugal. Moreover, it served as a research tool in many areas such as chemistry, biology, or the environment, and also participated in providing services to companies. It helped train several generations of students and was a work companion for many researchers at Ciências ULisboa,” says Carlos Cordeiro, professor at the Department of Chemistry and Biochemistry at Ciências ULisboa and coordinator of the Portuguese Mass Spectrometry Network.

Once Ophelia, Ophelia for life – but before being the Ophelia that made the eyes of those who wanted to discover the composition of the most varied molecules in the laboratories of Ciências ULisboa shine, the historic mass spectrometer began by treading its first chapter in the service of science at Utrecht University, in the Netherlands. Little is known about that period – and there is also no evidence or indication that the name was not transferred with the machine when it left for Lisbon. But there is a record of two women who are said to have played a providential role. And both made history in education at Ciências ULisboa.

“At the end of the 1970s, Tereza Robert Lopes, a professor at what was then the Department of Chemistry, sent her student Helena Florêncio to pursue a doctorate at Utrecht University. Helena Florêncio completed her doctorate under the supervision of Tereza Robert Lopes and Geo Dijkstra, who was a professor at Utrecht University. The doctorate was completed in 1979,” says Carlos Cordeiro.

Documentary evidence is scarce—and finding witnesses among research teams whose careers peaked in the 1970s and 1980s is also no easy task. But it would not be particularly unusual to deduce that both Tereza Robert Lopes and Helena Florêncio contributed to Utrecht University’s decision to donate the equipment to the University of Lisbon.

“Helena Florêncio played a decisive role in bringing these machines that changed the science done in the country,” emphasizes Carlos Cordeiro. “Possibly, it is not the first mass spectrometry equipment to operate in Portugal, but Ophelia, being an MS-902, can today be seen as the first modern equipment of its kind to arrive in the country. Simply put, we can see it as the first complete mass spectrometer to operate in Portugal,” adds the professor from Ciências ULisboa.

After being installed in the basement of building C1 still during the 1980s, Ophelia would later be transferred to one of the laboratories properly equipped to support such weight inside building C8. In a space of about 100 square meters, Ophelia left little room for much else—and that factor also contributed to its move to the museum, already in 2020. Carlos Cordeiro recalls that the equipment currently on display at MUHNAC, in reality, corresponds only to part of the paraphernalia necessary for a scientist to work on discovering, through electric charge and magnetic forces, which atoms make up any given molecule.

In addition to the equipment that housed the experiments and which is now at MUHNAC, Ophelia's day-to-day operations involved a console for controlling operations and collecting data, vacuum pumps, and many other devices that supported different functions. “At the time, the mass spectra (obtained with Ophelia) were reproduced on paper by thermal printers and required researchers to take measurements with rulers,” describes Carlos Cordeiro.

For several years, Carlos Cordeiro saw Ophelia operating without making much use of it himself. On the other hand, he clearly remembers the frequent incursions led by Helena Florêncio with groups of students and researchers around the machine. In 2005, the Portuguese Mass Spectrometry Network was created at the initiative of the Foundation for Science and Technology (FCT) and in response to numerous requests from academic entities. Unsurprisingly, Helena Florêncio was chosen as coordinator of this National Network. In turn, Carlos Cordeiro initially joined the network as coordinator of the Ciências ULisboa branch, becoming the national coordinator of the Network in 2017.

Having technology from the 70s, Ophelia was already showing “some signs of obsolescence” at the beginning of the 21st century, but it continued to operate as one of the main reference instruments in Ciências ULisboa. “It wasn’t suitable for experiments with biological molecules and that could be somewhat limiting, but it was very useful for other types of chemical reactions and that’s why it was used for many years,” says Carlos Cordeiro.

Mass spectrometry originated as a concept through the work of J.J. Thomson in the 19th century. The British researcher was the first to envision a way to estimate the mass of a molecule based on the electric charge it carries. The concept assumes that the electric charge of the particles that make up a molecule can be sufficient for it to follow a specific trajectory under a given magnetic force. This means that, indirectly, the trajectory taken by each molecule under the magnetic force can reflect its mass or the elements that compose it.

The concept paved the way for different types of mass spectrometry equipment in the following decades. Some of these technologies provide higher resolution depending on the observation time of the experiment, while others already operate with “delicate and vulnerable” molecules of biological origin. On the other hand, right after World War II, the equipment used in the study of radioactivity predominated. With technological evolution, models emerged that use rare gases which hardly bond with other chemical elements and therefore prove especially useful when it comes to breaking molecules apart and revealing their respective components.

“At the end of the 1960s, models began to appear that allow us to know the structures of molecules after collisions with particles of gases such as argon, helium, or xenon. In this way, the molecules to be studied are shattered… and become like a disassembled puzzle that allows us to know the various pieces that constitute it,” describes Carlos Cordeiro. “If a machine can determine the mass with a sufficient margin of approximation, we are able to know how many atoms or what types of atoms exist in a molecule. Basically, it gives us the information that corresponds to a chemical formula,” he adds.

As with all technologies and machines, Ophelia could not avoid the end: the last experiments must have taken place on a date yet to be determined between 2010 and 2012. By that time, Ciências ULisboa was already hosting the ZAB mass spectrometer, manufactured by VG, which was also donated by Utrecht University, and was already dealing with more complex mixtures than those analysed with Ophelia. Already in the 21st century, the National Mass Spectrometry Network benefits from a remarkable increase—and once again has Ciências ULisboa as its epicenter. This time, it was the arrival of a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR, in the English acronym).

“FT-ICR is today the top technology and it doesn’t seem like it will be surpassed anytime soon. In this type of equipment, the resolution (of measurements) can vary depending on the duration of the assay. Thus, time is also a variable that can be used. It was somewhat controversial due to its cost, but the FT-ICR machine we have running here has already been used to analyse samples from meteorites, insects, samples from the bottom of the Atlantic, tumours, gin, grapevines, saliva, fingerprints, and many others. All this was only possible due to the universality of mass spectrometry. It can’t be said that it replaced Ophelia’s technology, but it was a paradigm shift,” explains Carlos Cordeiro.

Considering that there will be only "20 to 30 pieces of equipment with the same technology in Europe," the FT-ICR is unlikely to stop operating any time soon. On the other hand, the ZAB is "on the way to being musealized" to ensure greater effectiveness in scientific outreach carried out near the C8 Library. Decidedly, Ophelia left a legacy.