Nowadays, everywhere we go in our daily lives we are surrounded by a slew of materials that affect our health in unknown ways, or in ways we know very little about. Working both in Finland and Sweden, FiDiPro Professor Anita Lloyd Spetz and her research team are studying the effects of particles on cells with novel test methods that utilise electrical measurements. The results of the research can provide new insights into health promotion.
“Nanomaterials, for instance, are equipped with features that can allow the materials to penetrate the skin and pass into the bloodstream when inhaled. It’s vital that we know more about the health effects of such materials. In our research, for example, we’re looking at how nanoscale titanium dioxide influences human cells. Nanoscale titanium dioxide is a common ingredient in products such as paint and sunscreen,” Lloyd Spetz says.
Pursuing improved test methods
Traditionally, the health effects of chemicals, pharmaceuticals, plastics and nanomaterials have been studied using animal testing. Today, however, there is increasing agreement among both researchers and regulators to reduce the use of animals in research, the argument being that animal testing is unethical and unnecessary. The European Union, for example, has banned cosmetics containing animal-tested ingredients.
“On the other hand, even animal testing doesn’t always produce reliable results. Different species can show a wide variety of responses to different substances, and the responses aren’t always comparable to human responses,” Lloyd Spetz explains. For example, the thalidomide (Neurosedyn) scandal in the late 1950s and early 1960s was partly caused by the use of animal experiments, since the drug was passed for use after being tested on rodents. Thalidomide, a drug that was used by pregnant women to combat morning sickness or as a harmless sleeping pill, caused thousands of babies worldwide to be born with malformed limbs. The drug had been tested only on rodents, and the tests had failed to demonstrate the dangerous side-effects.
Cell culture can yield good results, but not without posing certain challenges. While cell culture also requires a lot of work and includes many steps, the main problem is that measurement disturbs the culture to a degree where the process cannot be continued post-measurement.
Microchips to the rescue
Lloyd Spetz and her team are developing a next-generation cell culture technique that uses capacitance sensor microchips to evaluate cell culture viability.
“In the case of healthy cells, adherent cells normally attach to and spread out on surfaces,” Lloyd Spetz says. When a cell enters apoptosis and dies, it detaches from the surface. The microchip can act as a culture surface and researchers can monitor the cell attachment electrically.
The developed method holds many advantages over traditional forms of cell culture: it includes fewer stages, the cells can be computer-monitored in real-time, and the measurements will not interfere with the cell population. Because the microchip used in the measurements is exposed to physiological conditions, the next challenge is to find packaging materials and techniques that will not harm the cells but that can withstand the test conditions, such as temperatures and moisture.
“The most interesting question for us right now relates to packaging technology. How can we take a ceramic material and use it to manufacture water-resistant 3D modules? We develop tailor-made, three-dimensional packages for microchips.”
The team is now running its first tests to analyse whether the microchip can do what it is supposed to do. Another objective is to increase the degree of automation in the measurement system. The ultimate goal is to integrate several functions on a single chip so that the whole system can be used even outside the laboratory in real conditions.
Applications for better health
The applications based on the microchip face growing expectations to deliver on promises. Research into the health-related effects of nanomaterials is very important, because we still know very little about their biological effects. There are no long-term follow-up studies to go by, partly because nanomaterials have been in use for such a short while, starting in the early 2000s. Another key area of research is cancer research. In the future, the method being developed by Anita Lloyd Spetz and her team can be used to find the best medical cures for individual cancer patients.
The research project is a collaborative effort between the Microelectronics and Materials Physics laboratories of the University of Oulu, the University of Maryland and Linköping University. “Oulu packages the microchips and tests them during cell growth, Maryland supplies the chips, and Linköping takes care of the measurement software and additional sensors,” says Lloyd Spetz.
“One important thing about this project now is that the science will continue to be developed. Four years goes by so quickly when you’re working on something this big. I’m delighted that we have skilled researchers and students who will continue the research so that our work won’t go to waste when the project ends.”
About the research
FiDiPro Professor Anita Lloyd Spetz from the University of Oulu develops simple and inexpensive methods to detect potentially toxic effects of nanoparticles (NPs) on cells. The health status of cells during exposure to NPs is monitored in a CMOS-based cell clinic developed at the University of Maryland. The project is expected to create new knowledge, for example, related to the toxicity and synthesising of NPs, cell growth and sensor technology. Lloyd Spetz’s project is carried out in collaboration with the University of Maryland and Linköping University.
At Linköping University, Lloyd Spetz has a research group devoted to the development of chemical sensors for harsh environments.
Text: Marja Nousiainen