Projects / Programmes source: ARIS

Development of advanced electrochemical sensors for in vitro and in vivo studies of brain development and function

Research activity

Code Science Field Subfield
4.04.01  Biotechnical sciences  Veterinarian medicine  Morphology, physiology and animal reproduction 

Code Science Field
B000  Biomedical sciences   

Code Science Field
4.03  Agricultural and Veterinary Sciences  Veterinary science 
Brain, development, neurotransmitters, G protein coupled receptors, electrochemistry, biological sensors, CMOS transistors
Evaluation (rules)
source: COBISS
Researchers (14)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  29835  PhD Tomaž Budefeld  Microbiology and immunology  Researcher  2012 - 2014  92 
2.  25530  PhD Petra Draškovič  Biochemistry and molecular biology  Researcher  2011 - 2014  59 
3.  07850  PhD Marinka Drobnič-Košorok  Veterinarian medicine  Researcher  2011 - 2012  185 
4.  24348  PhD Neža Grgurevič  Veterinarian medicine  Researcher  2011 - 2013  57 
5.  18555  PhD Samo Hočevar  Chemistry  Researcher  2011 - 2014  242 
6.  32334  PhD Jasmina Kerčmar  Metabolic and hormonal disorders  Junior researcher  2011 - 2014  42 
7.  03494  PhD Marijan Maček  Electronic components and technologies  Researcher  2011 - 2014  178 
8.  13330  PhD Gregor Majdič  Veterinarian medicine  Head  2011 - 2014  575 
9.  32971  Uroš Nahtigal  Electronic components and technologies  Researcher  2011 - 2014  17 
10.  00130  PhD Anton Pleteršek  Electronic components and technologies  Researcher  2011 - 2012  207 
11.  00166  PhD Drago Strle  Electronic components and technologies  Researcher  2011 - 2014  244 
12.  01717  Rozana Škrbec    Technical associate  2011 - 2014 
13.  34286  Nina Šterman    Technical associate  2012 - 2014 
14.  13334  PhD Milka Vrecl Fazarinc  Veterinarian medicine  Researcher  2011 - 2014  263 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,277 
2.  0158  BIA, Laboratory and process equipment company, Ltd.  Ljubljana  5327601  18 
3.  0406  University of Ljubljana, Veterinary Faculty  Ljubljana  1627139  10,132 
4.  1538  University of Ljubljana, Faculty of Electrical Engineering  Ljubljana  1626965  27,564 
Studies of brain development and function are one of the main challenges in biomedical research today. Understanding how brain develops and function is a formidable task due to the complexity of the central nervous system and, to some extent due to lack of specific tools to examine brain development and function. Neural cells communicate between themselves through the synapses. At the synapse, neurotransmitters are released from the presynaptic cells and trigger specific response at the postsynaptic cells, thus propagating signals from one nerve cell to another. Therefore, neurotransmitters represent a way of communication between brain cells. Neurotransmitters are different molecules like peptides, monoamines, aminoacids, gases and others. Neurotransmitters could be measured in body fluids by classical methods such as RIA and ELISA or visualized in isolated brain tissues with methods like in situ hybridization and immunocytochemistry, but none of these methods could provide information about the release of neurotransmitters in live brain tissue in real time. In recent years, electrochemical methods were developed for measuring some neurotransmitters in living brain tissue, but these methods have limitations such as poor sensitivity, limited spatial resolution, limited number of neurotransmitters that could be measured, and there is a question whether electrochemical potential applied on such electrodes and corresponding electrical current could excite nerve cells. In the proposed studies, we will therefore develop a novel sensor, based on microarray technology that will be able to detect several different neurotransmitters in live brain tissue simultaneously, with precise spatial and temporal resolution, which will be used for in vitro studies with organotypic brain slices. In the initial phase of the project, we will construct a micro-sensor for simultaneous detection of serotonin and dopamine based on electrochemical impedance measurements with electrodes, already developed by a partner on the project. In the second phase of the project, we will develop completely novel microsensor array utilizing modified MEMS technology, with G protein coupled hormone receptors attached to the corresponding micro surfaces acting as detector molecules. Receptors for neurotransmitters will be selectively mobilized to the specific surface of the sensors in the array architecture using amphipols or liposomes as carrier molecules. Binding of the ligand to the specific receptor will be detected as a space and time dependent function using  array of differently modified sensors, whose change of impedance due to binding of the ligand will be measured with extreme sensitivity using low noise analog and digital signal processing that will be implemented in short channel CMOS technology. Therefore, in this project, a completely novel, very important tool for brain studies will be developed. This tool will be initially used in in vitro experiments studying brain development and function, but in further development (that is beyond the scope of this three years long project) we envision also a microsensor that could be used in vivo in both animals and humans. Development of such sensors will represent an important breakthrough that will enable completely new ways to study brain development and function and will be therefore important for wide field of neuroscience research in both veterinary and human medicine. Furthermore, development of such sensor will present an important technological achievement and such platform will be easily transferred into industrial production. In addition, the new sensor array could be used for other biotechnological and medical applications in veterinary and human medicine (such as novel diagnostic tools) as well as in food production industry.
Significance for science
We have developed a novel biosensor based on CMOS technology for detection of biological molecules, primarily neurotransmitters, although same technology could be used for other biological molecules. We have worked on functionalization of sensor surface with different methods. The project was technologically very demanding, but despite limited results due to low budget and short duration of the project, we have made some important contributions in the field of biosensors. The final results (which will be published soon) was functionalization of senior surface with appetisers, bound the the surface with nation membrane. To the best of our knowledge this is the first such successful development and will be as such useful in further development of similar sensors. Very important are also all negative results/problems we had with other methods such as originally proposed method of using g protein coupled receptors and functionalization with modified aptamers, which have shown that these methods in the current state of technology are not optimal for functionalization of the surface of CMOS based sensors.
Significance for the country
Further development of such sensors could have important contribution to technological developments of Slovenia. The original aim of the project was detection of neurotransmitters in the brain. However, similar technology could be used for detection of variety of biological molecules and as such, a similar sensors could have potential wide use in medicine, food industry and similar. Optimisation of such sensors would need further development and financing, which are at the moment lacking. Nevertheless, with additional funds we would be able to bring such sensor to the market in few years and we will therefore seeking additional funds to continue with this programme, especially based on very good results in the last year of the project.
Most important scientific results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
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