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I wanted to be an interdisciplinary scientist.
German version/Deutsche Version
Interdisciplinarity seems to have come naturally to her. Even during her Bachelor’s studies , one course of training alone did not cover her interests, so that in 2007, at the age of 21, she earned two bachelor’s degrees with honors, one in molecular biology and genetic engineering, the other in the biochemistry of cells and tissues. Even one university was not enough for her, so she included other institutions in her education. At Bogazici University, she was part of a research group working on neurodegeneration during her bachelor’s degree, and at Sabanci University and European Molecular Biology Laboratory, she entered the fields of microelectronics and bioinformatics during her doctoral thesis. Accordingly, Zeynep Altintas does not define her scientific aspirations by a specific field. She has a helicopter view. “I’m not a doctor, I’m not a nutritionist, I’m not an environmental engineer,” she says. “I’m a technologist. I develop biosensors.” These are measuring devices whose probes are inspired by biological structures, and which usually detect biological structures as well. To design them, Altintas combines an arsenal of methods ranging from biotechnology, bioinformatics and chemical analysis to polymer chemistry and electronics. The technologies she has developed help detect biomarkers in blood samples, bacteria in food and viruses in drinking water, for example.
The genius loci of Cranfield
“I was always curious about different fields of knowledge, beyond biology, chemistry and physics,” Altintas recalls. That’s why, she says, after she passed her two bachelor’s exams, she realized she didn’t want to be a molecular biologist. “I wanted to be an interdisciplinary scientist, although I did not yet know what interdisciplinarity means.” When she moved to Cranfield University in England, however, she soon found out. “That’s where my story with biosensors started.” That had to do with the genius loci in two ways. Cranfield was where Anthony Turner taught, a founding father of biosensing, developer of the best-selling blood glucose sensor and co-editor of the world’s first textbook on the fundamentals and applications of the discipline. Cranfield University also has one of its focal points in the applied sciences and offers only postgraduate programs – an excellent opportunity for Altintas to interact with other students at a high level. Focusing on lung cancer, she took up her PhD at Cranfield in 2009 on “Detection of biomarkers for cancer diagnosis using biosensor technologies,” which she completed in 2012. “Often young scientists focus on only one biosensor,” Altintas says, “I had the opportunity to do research with all types of biosensors at Cranfield from the beginning, and that has been a key factor in shaping my future career.”
A new type of receptor on the horizon
The biosensors Altintas learned to work with differed primarily in how they measure the interaction between a molecule to be detected and the biological receptor to which that analyte binds and translate it into an electrical signal proportional to the analyte’s concentration. Electrochemical, optical or piezoelectric methods are the tools of choice. Electrochemical methods respond to how the binding interaction changes currents or voltages that have been applied along the surface of the measurement system. Optical methods respond to how the intensity of the color signal changes when a fluorescently labeled analyte binds to its receptor. Piezoelectric methods, like a microbalance, use the property of quartz crystals to respond to mechanical pressure by generating an electrical voltage. The binding of analytes to receptors on or in a quartz layer is one such pressure. The biological receptors Altintas preferred to research with during her doctoral studies were antibodies and nucleic acids that specifically bound the biomarkers she was studying. But her tools also included aptamers, relatively short single-stranded DNA or RNA molecules. A completely different type of biorecognition receptor was just appearing on the horizon at the time – the MIPs, in the production and application of which Zeynep Altintas was soon to take a leading role.
On the way to becoming an expert for nanoMIP
MIP is the abbreviation for molecularly imprinted polymers. They bear imprinted cavities to act as binding pockets for certain analytes as tiny as antibodies or parts thereof. Although nanoMIPs had been developed for the detection of chemical pollutants as early as the mid-1990s, it was not until 2010 that the biocompatibility of these polymers in the form of soluble nanogels had matured enough to make them suitable for biomedical applications. In the production of such nanoMIPs, monomeric building blocks are linked together to form polymers in the presence of the analyte they are intended to detect. The analyte leaves complementary cavities in the resulting polymer and is then extracted. “For this manufacturing process, you need a good knowledge of polymer chemistry and surface chemistry,” Altintas says. “I had acquired those in my second bachelor’s degree.” Cranfield scientists had played an important role in the development of biologically usable nanoMIP. When she returned to Cranfield as a postdoctoral researcher after completing her doctorate, Zeynep Altintas immediately devoted all her energy to the burgeoning field of nanoMIP. Together with a colleague, she invented a patented method for their solid-state synthesis. Back in the fall of 2013, she was named a faculty member at the Cranfield School of Engineering. At the time, the nanoMIP folks were still working primarily with chromatographic detection methods, Altintas says; she was one of the first to look for ways to connect these artificial antibodies to sensors. And she did so with great success. When she took over as head of the biosensor and receptor development group at the Department of Chemical Engineering at Technische Universität Berlin in 2016, her reputation as an excellent expert on nanoMIP long preceded her. Whereby, as she points out, she also develops biosensors with other nanodetectors, such as tiny magnetic particles or graphene quantum dots.
Suitable for any application
She still works with antibodies, says Altintas, to which she has no scientific objections. In practice, however, there are a number of arguments against them. For the production of antibodies, animals are needed, and she doesn’t like that because she loves animals. In addition, the production of antibodies takes up to six months and is very expensive. The MIP receptors, on the other hand, she says, can be produced in five days or less, sometimes in as little as five minutes, at no great cost. They can be easily stored with a shelf life of more than a year, while antibodies can be stored for six months at most, even under special storage conditions. “Sometimes we need to do our measurements at extreme pH or temperatures, and antibodies as biological molecules are not suitable for that.” In contrast, MIPs are suitable for every conceivable application, she says.
Epitopes for tumor diagnostics
Conventional MIPs, however, have a disadvantage: they do not bind the analytes they are supposed to detect as well as antibodies. To change that, Altintas uses computer-aided design. She calculates binding affinities and plays with structures in virtual space to determine the best manufacturing recipes for molecularly imprinted polymers. She designs digital models of MIP that show particularly strong interactions with their target molecules. However, this interaction does not involve the entire large target molecule, but only a small part of its surface, an epitope. “We find out which epitope offers the best way for a usually huge protein to be recognized. Then we identify the functional monomers best suited for being imprinted with that epitope.” In this way, Altintas and a group at TU Berlin succeeded in isolating particularly stable epitopes of the lung cancer marker NSE and using them as “imprinting stamps” for tumor diagnostics, which can be produced relatively quickly and cheaply.[1]
At the service of global health
Zeynep Altintas is involved in an impressive variety of projects. For example, she has developed the prototype of a particularly sensitive biosensor for heart attack diagnostics. It measures the binding of the marker troponin I to epitope-imprinted nano-MIP by surface plasmon resonance. Another challenge is viruses in drinking water. She started working on this right after her doctorate as part of an EU funding program. Such viruses are contagious even in low concentrations and endanger the health of nearly one billion people, especially in the global South. Their detection has so far been very complex, and their complete removal is usually impossible. Nano-MIP-based biosensors are set to change that. They are fitted with chips that recognize each virus by its specific epitopes.[2] Embedded in membrane filters, such bioselective nanoMIP-incorporated systems can reliably purify contaminated water. Zeynep Altintas’ work in this field is well advanced and has been funded by the German Research Foundation since 2019. Assessing the quality and compatibility of food more accurately and efficiently is another task Altintas has dedicated herself to. Using automated biosensor platforms, she is involved in determining their natural and artificial additives, assessing their freshness and shelf life, detecting bacterial contamination, allergens or traces of heavy metals. At Kiel University, where she was appointed to a permanent professorship in December 2021 a few months after receiving the Life Sciences Bridge Award from the Aventis Foundation, she is part of an EU-funded team developing mini-sensors that measure the concentrations of nitrate, ammonium and phosphate in the soil around the clock to counteract the overfertilization of agricultural soils.
The cooperative climate of Kiel
“I’m still working with colleagues in Berlin,” says Zeynep Altintas, “but I’m focusing more and more on my tasks in Kiel.” There, she conducts research in close proximity to the medical faculty, which does not exist at the TU Berlin and is interested in her technologies. There, for example, she is pushing ahead with the project of a biosensor integrated into a wristwatch that derives parameters via the skin that provide information about the circadian rhythm of its wearer. She maintains a close exchange with colleagues from electrical engineering to realize her bio-inspired ideas in “lab-on-a-chip” concepts. Altintas says she believes it won’t be long before some of her research results are ready for the market. But her capacity to take care of their translation herself is limited, she says. “My time is taken up with acquiring funding, hiring and training staff, teaching, writing textbooks and doing research.” With the support of the relevant offices at Kiel University, however, she has recently been focusing more on the possibilities of technology transfer.
Author: Joachim Pietzsch, Wissenswort
Photos: © Uwe Dettmar
[1] Z. Altintas*, A. Takiden, T. Utesch, M.A. Mroginski, B. Schmid, F.W. Scheller, R.D. Sussmuth. Integrated approaches toward high-affinity artificial protein binders obtained via computationally simulated epitopes for protein recognition. Advanced Functional Materials, 29 (15): 1807332, 2019.
[2] Z. Altintas*, M. Gittens, A. Guerreiro, K.A. Thompson, J. Walker, S. Piletsky, I.E. Tothill. Detection of waterborne viruses using high affinity molecularly imprinting polymers. Analytical Chemistry, 87: p. 6801-6807, 2015.