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Projects / Programmes source: ARIS

Biopharmaceuticals: sensor for aggregation of protein particles based on liquid crystals

Research activity

Code Science Field Subfield
1.02.01  Natural sciences and mathematics  Physics  Physics of condesed matter 

Code Science Field
P002  Natural sciences and mathematics  Physics 

Code Science Field
1.03  Natural Sciences  Physical sciences 
Keywords
soft matter, sensor, liquid crystals, biopharmaceuticals, proteins
Evaluation (rules)
source: COBISS
Researchers (24)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  38008  PhD Jure Aplinc  Physics  Researcher  2017 - 2018  24 
2.  33694  PhD Dejan Arzenšek  Physics  Researcher  2017 
3.  33760  PhD Lamprini Athanasopoulou  Physics  Researcher  2019 - 2020 
4.  33197  PhD Simon Čopar  Physics  Researcher  2017 - 2020  160 
5.  29523  PhD Anton Gradišek  Physics  Researcher  2018  435 
6.  37473  PhD Uroš Jagodič  Physics  Researcher  2017 - 2020  26 
7.  34670  PhD Biljana Janković  Pharmacy  Researcher  2018 - 2020  137 
8.  12942  PhD Janez Kerč  Pharmacy  Researcher  2018 - 2020  240 
9.  16408  PhD Klemen Kočevar  Physics  Researcher  2018 - 2020  63 
10.  37526  PhD Žiga Kos  Physics  Researcher  2017 - 2019  75 
11.  18355  PhD Drago Kuzman  Physics  Researcher  2017 - 2020  64 
12.  03321  Ivan Kvasić  Physics  Technical associate  2017 - 2020  22 
13.  37364  PhD Jaka Marušič  Chemistry  Researcher  2017 
14.  36351  PhD Maruša Mur  Physics  Researcher  2017 - 2020  21 
15.  09089  PhD Igor Muševič  Physics  Researcher  2017 - 2020  750 
16.  35477  PhD Gregor Posnjak  Physics  Researcher  2017 - 2020  34 
17.  25670  PhD Miha Ravnik  Physics  Head  2017 - 2020  435 
18.  12338  PhD Miha Škarabot  Physics  Researcher  2017 - 2020  253 
19.  37811  Mitja Štimulak  Mechanics  Researcher  2019  28 
20.  38041  Ana Šušterič  Physics  Researcher  2017 
21.  26467  PhD Uroš Tkalec  Physics  Researcher  2018 - 2020  213 
22.  11035  PhD Aleksander Zidanšek  Physics  Researcher  2018  360 
23.  39544  Mitja Zidar  Physics  Researcher  2017 - 2018  12 
24.  07110  PhD Slobodan Žumer  Physics  Researcher  2017  1,026 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,624 
2.  0258  Lek Pharmaceutical Company d.d.  Ljubljana  1732811  8,424 
3.  1554  University of Ljubljana, Faculty of Mathematics and Physics  Ljubljana  1627007  34,059 
Abstract
Controlling and understanding protein aggregation is today an open fundamental and applied challenge in the development and production of proteins as biopharmaceuticals, affecting their functionality, safety, purification, stability of solutions, packaging, and transport methods. The aggregation of proteins typically depends not only on the exact molecular structure of the proteins but also on multiple (micro-) environmental parameters, including temperature, pH, buffers, surfactants, stabilisers and tonicifiers, which from biopharmaceutics perspective, requires multiple screenings of diverse protein systems before final solutions –the biological drugs- can be developed and sent to market. However, there exist very few robust and efficient methods for screening of aggregation over a broad range of proteins and over broad scale of aggregate sizes, where especially detection of subvisible protein aggregate particles is a major challenge. Therefore, developing such technology and boost fundamental knowledge in this direction would be of major advantage to the field of biopharmaceuticals. Here, the main goal of this soft matter applied physics proposal is to develop an entirely new line of sensors for protein aggregation based on liquid crystalline fluids and to explore the role of interfaces on protein aggregation, as of direct relevance to the biopharmaceutical industry. The core mechanism of this proposal will be the performance of liquid crystalline fluids as optical detector materials where the sensing will be based on the selective absorption of proteins and/or their aggregates at the protein solution-liquid crystal interface. The presence of the aggregates will result in the changes in the molecular order of the liquid crystalline fluids, which will then be detected with various non-contact optical methods. Such approach will create highly-sensitive and (~ms) fast-responsive optical sensors for aggregation with the sought-for window for detection ranging from visible to deeply sub-visible aggregate particles. Of particular scientific relevance and conceptual advance will be questions on: (i) the role of geometry and topology of the interfaces on the protein aggregation, (ii) the effect of interfaces on the size and characteristics of aggregates, as well as the surface aggregation dynamics, and (iii) the use of light and/or plasmonics as possible mechanism for the control and even reverse of the aggregation. Methodologically, the project will develop new approaches for the detection of protein aggregates at the interfaces, based on polarisation, fluorescence, and STED microscopy as well as optical spectroscopy, which are all state-of-the-art approaches in fundamental and applied challenges of modern biotechnology and sciences in general. The project will be realised by the soft matter group in Ljubljana and the biopharmaceuticals group at company Lek d.d., part or Novartis, the industrial partner of this proposal, which are both world strong groups in their fields distinguished by their joint theoretical and experimental work and high scientific standards; e.g. proposal-related publications include PNAS 2016, Nature Comm. 2016, Sci. Rep. 2016, and Nature Phys. 2015. The socio-economic deliverables of the project are designed to yield distinct outreach, contribute to the excellence of Slovenia and abroad, and contribute new fundamental and applied knowledge to Slovenian (bio)pharmaceutical industry. Finally, this proposal is aiming at the fundamental and applied cutting edge of the state-of-the-art of biopharmaceutics, to create novel scientific and technological pathways for controlling the organisation of bio-relevant macromolecules at the microscopic and macroscopic level.
Significance for science
The 21st century is often termed as the BioTech century, with the ultimate challenge and goal to establish control over life and life mechanisms by using science and technology, where even small successes can not only move science into novel heights, but more importantly serve to the benefit of humankind in general. We are proposing an ambitious applied research project which is at the top-edge of the modern soft matter science and biopharmaceutics, actually establishing a pathway for direct transfer of knowledge and technology between the two fields at fundamental and applied level. The main scientific impact of this proposal will be to explore the protein aggregation phenomena as affected by the interfaces, which is a result that can affect both fundamental and applied concepts in bio-technology, pharmacy, medicine, and condensed matter science. Of particular scientific relevance and conceptual advance will be questions on: (i) the role of geometry and topology of the interfaces on the protein aggregation, (ii) the effect of interfaces on the size and characteristics of aggregates, as well as the aggregation dynamics, and (iii) use of light and/or plasmonics as possible mechanism for the control of the aggregation. As the major methodological impact, the project will develop new approaches for the detection of aggregation of proteins at the interfaces, based on polarisation, fluorescence, and STED microscopy as well as optical spectroscopy. The project group of this proposal has the unique needed joint knowledge – both experimental and theoretical – on the state-of-the-art use of soft matter complex fluids and applied use of proteins as biopharmaceuticals to approach such fundamental and applied challenge. To generalize, this proposal is aiming at the cutting edge of the state-of-the-art and future biotechnology, to create novel scientific and technological pathways for controlling the organisation of bio-relevant macromolecules at the microscopic and macroscopic level.
Significance for the country
Slovenia identified Biopharmaceuticals, the topic of the current proposal, as one of the focus of its Smart specialisation in S4 priority area Health-Medicine. Slovenian alignment with this strategy to support biopharmaceuticals was recently confirmed by the decision to co-finance 4 years program “New generation of biological drugs – Biopharm.Si” with up to 6.0 million euros, which is an action which will involve SMEs, large biopharma company Lek and newly established enterprises that will in combination with research organization create a critical mass of excellent players and position Slovenia as one of the global pillars in the field of biologics development. The proposed project is in contrast to Biopharm.Si focused on the development of innovative sensor/method to control the stability of biological drug which is especially essential in the phases that follow bioprocess – i.e. drug purification, storage and final dosage formulation – all essential process in the deliverance of biological drugs on the market. Slovenia has exceptional and world class capacities (please see the references of the partners) in – on the first glance – non related areas of biopharmaceuticals, liquid crystals physics and soft matter science. We strongly believe, that we can be – as far as we know – the first in the world to integrate those areas and offer to Slovenia and biopharma industry a niche high-technology product enabling faster development of stable biological drugs. Taking into account that the cost of biological drug exceeds hundreds of millions euros, the proposed innovative sensors have great potential for costs savings in biopharma and consequently a clear business case for a start-up company dealing with sensors to monitor aggregation of biological drugs.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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