Diamonds – highly desirable lumps of carbon. But while their use to jewellers is well known, their hidden secrets are being revealed by the DIADEMS project. By modifying the structure of a diamond crystal, the project creates a new material that could be used in applications, from the creation of smart medicines to the next generation computers. The EU project is helping Europe stay at the forefront of research into atomic scale sensors. 
The DIADEMS (DIAmond Devices Enabled Metrology and Sensing) project is replacing a single atom in a diamond crystal with one of nitrogen, known as ‘doping’. By trapping nitrogen in the crystal, researchers can produce an atom-like structure with intrinsic magnetic properties obeying quantum mechanics.
Life sciences, physics, chemistry – wherever magnetic fields play a role, DIADEMS’ work could make a difference. A world of applications opening up The innovative ability to see how molecules react by reading changes in the spin of their electrons means researchers will be able to analyse exactly what is happening in chemical reactions at molecular and atomic scale. ‘A wide range of applications start to appear because we are able to monitor so precisely,’ says Debuisschert. Computing could benefit too as the sensors can be used in the development of small, high density storage discs with far greater capacity and reliability. ‘The capacity of data storage discs is getting ever bigger, squeezing the size of the magnetic domains used to store the information. By working at the atomic and molecular level, we could be able to control those storage devices at the scale required for high density storage,’ he adds. Results for research Debuisschert is fascinated by the combination of atomic physics and quantum mechanics and how it can yield practical applications. ‘We are in an industrial context, so we have to show that there are real, marketable applications at the end of the research.’ The fact that DIADEMS is using lab grown diamonds working at room temperature means once ready, its technology will be easier to apply and market. ‘Even so,’ says Debuisschert, ‘since we are still at a research level, EU funding at this stage is indispensable.’ The benefits of working at EU level While the project would not exist without the EU funding, Debuisschert feels a particularly important aspect of an EU-wide project is the collaboration between the 15 partners with a mix of academic and industrial partners. ‘We can be directly informed of all recent results coming out of EU labs, which saves a lot time, and we can share ideas in a way that is specific to European projects,’ he explains. ‘This helps us stay competitive in comparison with the big competitors abroad.’ The project which runs for four years, kicked off in September 2013. It is backed by EU support, via the Future and Emerging Technologies scheme, to the tune of EUR 6 million.
The DIADEMS (DIAmond Devices Enabled Metrology and Sensing) project is replacing a single atom in a diamond crystal with one of nitrogen, known as ‘doping’. By trapping nitrogen in the crystal, researchers can produce an atom-like structure with intrinsic magnetic properties obeying quantum mechanics.
‘This means that we can ultimately create tiny sensors that detect small magnetic signals. For example, these magnetic signals would allow us to monitor the electrical activity of neurons on a diamond slide and see how they operate together,’ explains Dr Thierry Debuisschert, project coordinator of DIADEMS, based at Thales, France.
‘In the future, we may be able to see whether or not a neuron is responding to a chemical being used for treatment.’ This outcome would benefit research into neurodegenerative diseases such as Alzheimer’s.
Life sciences, physics, chemistry – wherever magnetic fields play a role, DIADEMS’ work could make a difference. A world of applications opening up The innovative ability to see how molecules react by reading changes in the spin of their electrons means researchers will be able to analyse exactly what is happening in chemical reactions at molecular and atomic scale. ‘A wide range of applications start to appear because we are able to monitor so precisely,’ says Debuisschert. Computing could benefit too as the sensors can be used in the development of small, high density storage discs with far greater capacity and reliability. ‘The capacity of data storage discs is getting ever bigger, squeezing the size of the magnetic domains used to store the information. By working at the atomic and molecular level, we could be able to control those storage devices at the scale required for high density storage,’ he adds. Results for research Debuisschert is fascinated by the combination of atomic physics and quantum mechanics and how it can yield practical applications. ‘We are in an industrial context, so we have to show that there are real, marketable applications at the end of the research.’ The fact that DIADEMS is using lab grown diamonds working at room temperature means once ready, its technology will be easier to apply and market. ‘Even so,’ says Debuisschert, ‘since we are still at a research level, EU funding at this stage is indispensable.’ The benefits of working at EU level While the project would not exist without the EU funding, Debuisschert feels a particularly important aspect of an EU-wide project is the collaboration between the 15 partners with a mix of academic and industrial partners. ‘We can be directly informed of all recent results coming out of EU labs, which saves a lot time, and we can share ideas in a way that is specific to European projects,’ he explains. ‘This helps us stay competitive in comparison with the big competitors abroad.’ The project which runs for four years, kicked off in September 2013. It is backed by EU support, via the Future and Emerging Technologies scheme, to the tune of EUR 6 million.
This is a 3-D model of IBN's rapid test kit that detects dengue-specific antibodies. (Image: IBN, A*STAR) IBN Executive Director Professor Jackie Y. Ying shared, "Our rapid diagnostic kit can detect a key dengue antibody from saliva that is present in early-stage secondary infection. The ability to differentiate between primary and secondary dengue infections makes it a valuable early diagnosis tool that would help to ensure timely treatment and proper care of patients." Patients with secondary infection, who have previously been infected with other serotypes of dengue virus, stand a higher risk of developing dengue hemorrhagic fever or dengue shock syndrome. According to Singapore's National Environment Agency, dengue fever and its more severe form, dengue hemorrhagic fever, are the most common mosquito-borne viral diseases in the world. This disease poses a serious health threat, and is a leading cause of illness and death in tropical and subtropical climates. There are four known serotypes of the dengue virus but no vaccine or medicine has been developed to treat the illness. The incubation period before symptoms develop generally ranges from 4 to 10 days after infection. Therefore, early diagnosis would enable the patient to receive prompt medical attention and avoid further complications. Currently, dengue infection is diagnosed in the laboratory by testing the patient's blood sample for the presence of dengue antigens or antibodies. IBN's device, on the other hand, is capable of detecting IgG, a dengue-specific antibody found at the onset of secondary infections, directly from saliva in one step. Unlike blood samples, saliva can be collected easily and painlessly for rapid point-of-care diagnostics. However, unlike other body fluids, it cannot be applied directly to commercially available test kits as it would cause the sensor nanoparticles to stick haphazardly to the test strip. In addition, conventional paper-based tests are not designed to handle the larger sample volume of saliva required. As described in the journal ("A stacking flow immunoassay for the detection of dengue-specific immunoglobulins in salivary fluid"), the IBN researchers used an innovative stacking flow design to overcome key challenges faced by existing lateral flow designs, such as those used in pregnancy test kits. In IBN's device, different flow paths are created for samples and reagents through a multiple stacked system. This allows the saliva sample to flow separately through a fiber glass matrix, which removes the substances that would interfere with the nanoparticle-based sensing system before it mixes with the sensor nanoparticles. IBN's device configuration also helps to regulate the flow in the test strip, generating uniform test lines for more accurate results. IBN's diagnostic kit can also be adapted to detect other infectious diseases such as HIV and Syphilis. The IBN researchers are also investigating the use of other common fluid samples, such as blood, urine and serum for rapid, high-sensitivity test kits. The Institute is currently collaborating with ARKRAY Inc., a pioneer in the field of automated analysis systems, to commercialize its paper-based diagnostic technology. In 2013, ARKRAY opened its first Asian research center outside Japan in IBN with an investment of S$9.1 million over five years. The research center is focused on developing novel detection kits for infectious diseases based on IBN's innovative diagnostic platforms. Mr. Atsushi Murakami, General Manager of the R&D Division of ARKRAY Inc., said: "We have developed an excellent working relationship with IBN over the past two years, and our research activities have progressed rapidly. Together, we will continue to focus on the successful commercialization of new technologies for the diagnosis of tropical infectious diseases." IBN has been focused on research in medical technologies since 2003, and has created unique devices and assays for the rapid and accurate diagnosis of diseases. The institute has an active portfolio of 500 patents/patent applications, of which 86 have been licensed. It has spun off seven companies in the medical technology sector and its innovations have attracted major interest from the industry.
Quantum chemical models are used to form a picture of the forces and tensions at play between the atoms and electrons of a molecule,” says Simen Reine (left) and Trygve Helgaker, who for the last thirty years has taken the international lead on the design of a computer system for calculating quantum chemical reactions in molecules. Quantum chemical calculations are needed to explain what happens to the electrons’ trajectories within a molecule. Consider what happens when UV radiation sends energy-rich photons into your cells. This increases the energy level of the molecules. The outcome may well be that some of the molecules break up. This is exactly what happens when you sun-bathe. “The extra energy will affect the behaviour of electrons and can destroy the chemical bonding within the molecule. This can only be explained by quantum chemistry. The quantum chemical models are used to produce a picture of the forces and tensions at play between the atoms and the electrons of a molecule, and of what is required for a molecule to dissociate,” says Trygve Helgaker. The absurd world of the electrons The quantum chemical calculations solve the Schrödinger equation for molecules. This equation is fundamental to all chemistry and describes the whereabouts of all electrons within a molecule. But here we need to pay attention, for things are really rather more complicated than that. Your high school physics teacher will have told you that electrons circle the atom. Things are not that simple, though, in the world of quantum physics. Electrons are not only particles, but waves as well. The electrons can be in many places at the same time. It’s impossible to keep track of their position. However, there is hope. Quantum chemical models describe the electrons’ statistical positions. In other words, they can establish the probable location of each electron. The results of a quantum chemical calculation are often more accurate than what is achievable experimentally. Among other things, the quantum chemical calculations can be used to predict chemical reactions. This means that the chemists will no longer have to rely on guesstimates in the lab. It is also possible to use quantum chemical calculations in order to understand what happens in experiments. Enormous calculations The calculations are very demanding. “The Schrödinger equation is a highly complicated, partial differential equation, which cannot be accurately solved. Instead, we need to make do with heavy simulations”, says researcher Simen Kvaal. The computations are so demanding that the scientists use one of the University’s fastest supercomputers. “We are constantly stretching the boundaries of what is possible. We are restricted by the available machine capacity,” explains Helgaker. Ten years ago it took two weeks to carry out the calculations for a molecule with 140 atoms. Now it can be done in two minutes. “That’s 20,000 times faster than ten years ago. The computation process is now running 200 times faster because the computers have been doubling their speed every eighteen months. And the process is a further 100 times faster because the software has been undergoing constant improvement,” says senior engineer Simen Reine. This year the research group has used 40 million CPU hours, of which twelve million were on the University’s supercomputer, which is fitted with ten thousand parallel processors. This allows ten thousand CPU hours to be over and done with in 60 minutes. “We will always fill the computer’s free capacity. The higher the computational capacity, the bigger and more reliable the calculations.” Thanks to ever faster computers, the quantum chemists are able to study ever larger molecules. Today, it’s routine to carry out a quantum chemical calculation of what happens within a molecule of up to 400 atoms. By using simplified models it is possible to study molecules with several thousand atoms. This does, however, mean that some of the effects within the molecule are not being described in detail. The researchers are now getting close to a level which enables them to study the quantum mechanics of living cells. “This is exciting. The molecules of living cells may contain many hundred thousand atoms, but there is no need to describe the entire molecule using quantum mechanical principles. Consequently, we are already at a stage when we can help solve biological problems.” Hunting for the electrons of the insulin molecule The chemists are thus able to combine sophisticated models with simpler ones. “This will always be a matter of what level of precision and detail you require. The optimal approach would have been to use the Schrödinger equation for everything.” 
Working with Aarhus University, Simen Reine has calculated the tensions between the electrons and atoms of an insulin molecule. An insulin molecule consists of 782 atoms and 3,500 electrons. (Illustration: Simen Reine-UiO) By way of compromise they can give a detailed description of every electron in some parts of the model, while in other parts they are only looking at average numbers. “We are always having to find a good balance between the details we need and those we don’t need.” Simen Reine has been using the team’s computer program, while working with Aarhus University, on a study of the insulin molecule. An insulin molecule consists of 782 atoms and 3,500 electrons. “All electrons repel each other, while at the same time being pulled towards the atom nuclei. The atom nuclei also repel each other. Nevertheless, the molecule remains stable. In order to study a molecule to a high level of precision, we therefore need to consider how all of the electrons move relative to one another. Such calculations are referred to as correlated equations and are very reliable.” A complete correlated equation of the insulin molecule takes nearly half a million CPU hours. If they were given the opportunity to run the program on the University’s supercomputer, the calculations would theoretically take two days. “In ten years, we’ll be able to make these calculations in two minutes.” Medically important Vice Rector Knut Fægri at the University of Oslo points out that quantum chemical calculations may become important to life sciences. “Quantum chemical calculations can help describe phenomena at a level that may be difficult to access experimentally, but may also provide support for interpreting and planning experiments. Today, the calculations will be put to best use within the fields of molecular biology and biochemistry,” says Knut Fægri. Associate Professor Michele Cascella at the Centre for Theoretical and Computational Chemistry has recently been recruited from Italy to introduce quantum chemistry into life sciences. “Quantum chemistry is a fundamental theory which is important for explaining molecular events, which is why it is essential to our understanding of biological systems,” says Michele Cascella. By way of an example, he refers to the analysis of enzymes. Enzymes are molecular catalysts that boost the chemical reactions within our cells. Cascella also points to nanomedicines, which are drugs tasked with distributing medicine round our bodies in a much more accurate fashion. “In nanomedicine we need to understand physical phenomena on a nano scale, forming as correct a picture as possible of molecular phenomena. In this context, quantum chemical calculations are important,” explains Michele Cascella. Proteins and enzymes Professor K. Kristoffer Andersson at the Department of Biosciences uses the simpler form of quantum chemical calculations to study the details of protein structures and the chemical atomic and electronic functions of enzymes. “It is important to understand the chemical reaction mechanism, and how enzymes and proteins work. Quantum chemical calculations will teach us more about how proteins go about their tasks, step by step. We can also use the calculations to look at activation energy, i.e. how much energy is required to reach a certain state. It is therefore important to understand the chemical reaction patterns in biological molecules in order to develop new drugs,” says Andersson. His research will also be useful in the search for cancer drugs. He studies radicals, which may be important to cancer. Among other things, he is looking at the metal ions function in proteins. These are ions with a large number of protons, neutrons and electrons. Photosynthesis Professor Einar Uggerud at the Department of Chemistry has uncovered an entirely new form of chemical bonding through sophisticated experiments and quantum chemical calculations. Working with research fellow Glenn Miller, Professor Uggerud has found an unusually fragile key molecule, in a kite-shaped structure, consisting of magnesium, carbon and oxygen. The molecule may provide a new understanding of photosynthesis. Photosynthesis, which forms the basis for all life, converts CO2 into sugar molecules. The molecule reacts so fast with water and other molecules that it has only been possible to study in isolation from other molecules, in a vacuum chamber. “Time will tell whether the molecule really has an important connection with photosynthesis,” says Einar Uggerud.