Label-free experimental platforms in pharmaceutical research

One of our main research aims is to develop novel complementary real-time label-free in vitro tools for existing static biological assays and animal tests in the field of preclinical drug research and drug discovery. Current functional in vitro biochemical and cell culture assays used in pharmaceutical and life science research are static and only shed light on the endpoint equilibrium. They also require secondary detection techniques, such as UV-VIS spectrometry, UPLC, HPLC and fluorescence microscopy. On the contrary, drug delivery, in vivo, depends on dynamic processes. The use of labels is common in traditional biochemical and cell culture assays as well as in fluorescence microscopy, however the main drawback of this approach is that derivatization with fluorescent probes can change the behavior and properties of drug molecules or drug delivery systems, or even cell behavior. Therefore, promising in vitro results are often not followed by respective success in vivo. In addition, animal tests have been criticized for ethical and economic reasons. Thus, there is a clear need for real-time label-free biomimetic in vitro assays that allows one to monitor, detect and distinguish between drug and nanoparticle induced cellular processes, such as target specific drug induced cell signaling pathways and cell uptake mechanisms. We have, for several years, been developing real-time label-free platforms based on surface plasmon resonance in combination with living cell sensing and quartz crystal microbalance in combination with lipid bilayers as cell model layers for assessing drug and nanoparticle targeting and delivery efficacy. Recently, we have also introduced a novel time-gated Raman spectroscopy and surface-enhanced Raman scattering as label-free techniques for characterizing and detecting drugs, nanoparticles, extracellular vesicles, bacteria and biofilms. Our publications in this area of research are linked below.

 

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Publications in this area:

 

Marco G. Casteleijn, Dominique Richardson, Petteri Parkkila, Niko Granqvist, Arto Urtti and Tapani Viitala: Spin coated chitin films for biosensors and its analysis are depended on chitin-surface interactions. Coll. Surf. A 539, pp. 261–272 (2018).

Sanna Uusitalo, Martin Kögler, Anna-Liisa Välimaa, Jarno Petäjä, Ville Kontturi, Samuli Siitonen, Riitta Laitinen, Matti Tapani Kinnunen, Tapani Viitala and Jussi A. Hiltunen: Stability optimization of microbial surface-enhanced Raman spectroscopy detection with immunomagnetic separation beads. Opt. Eng. 56(3), pp. 037102 (2017).

Tiina Virtanen, Satu-Pia Reinikainen, Martin Kögler, Mika Mänttäri, Tapani Viitala and Mari Kallioinen: Real-time fouling monitoring with Raman spectroscopy. J. Membr. Sci. 525, pp. 312–319 (2017).

Teemu Suutari, Tiina Silen, Heikki Saari, Didem Sen Karaman, Diti Desai, Jessica Rosenholm, Martina Hanzlikova, Marjo Yliperttula and Tapani Viitala: Real-time label-free monitoring of cell interactions of various nanoparticles. Small 12(45), pp. 6289–6300 (2016).

Habib Baghirov, Didem Şen Karaman, Tapani Viitala, Alain Duchanoy, Yan-Ru Lou, Veronika Mamaeva, Evgeny Pryazhnikov, Marjo Yliperttula, Leonard Khiroug, Cecilia Sahlgren and Jessica M. Rosenholm: Feasibility study of the permeability and uptake of mesoporous silica nanoparticles across the blood-brain barrier. PLoS One 11, e0160705 (2016).

S. Uusitalo, M. Kögler, A.-L. Välima, A. Popov, Y. Ryabchikov, V. Kontturi, S. Siitonen, J. Petäjä, R. Laitinen, M. Kinnunen, A. E. Bunker, T. Viitala,  J. Hiltunen: Development of listeria detection on disposable SERS substrates with gold nanoparticles. RSC Adv. 6, pp. 62981-62989 (2016).

Martin Kögler, Bifeng Zhang, Yunjie  Shi, Marjo  Yliperttula, Timo  Laaksonen, Tapani Viitala, Kaisong Zhang: Real-time Raman based approach for identification of biofouling. Sens. Actuator B-Chem. 230, pp. 411–421(2016).

Tatu Rojalin, Lauri Kurki, Timo Laaksonen, Tapani Viitala, Juha Kostamovaara, Keith C. Gordon, Sebastian Wachsmann-Hogiu, Clare J. Strachan and Marjo Yliperttula: Fluorescence-Suppressed Time-Resolved Raman Spectroscopy of Pharmaceuticals. Anal. Bioanal. Chem. 408, pp. 761-774 (2016).

S. Uusitalo, M. Kögler, A.-L. Välimaa, A. Popov, Yu. Ryabchikov, V. Kontturi, S. Siitonen, J. Petäjä, T. Virtanen, R. Laitinen, M. Kinnunen, I. Meglinski, A. Kabashin, A. Bunker, T. Viitala and J. Hiltunen: Detection of Listeria innocua on roll-to-roll produced SERS substrates with gold nanoparticles. RSC Adv. 6, pp. 62981 – 62989 (2016).

Peng Liu, Tapani Viitala, Alma Kartal, Huamin Liang, Timo Laaksonen, Jouni Hirvonen and Leena Peltonen: Interaction Studies Between Indomethacin Nanocrystals and PEO/PPO Copolymer Stabilizers. Pharm. Res. 32, pp. 628-639 (2015).

Niko Granqvist, Huamin Liang, Terhi Laurila, Janusz Sadowski, Marjo Yliperttula and Tapani Viitala: Characterizing ultrathin and thick organic layers by surface plasmon resonance multi-wavelength and waveguide mode analysis. Langmuir 29, pp. 8561-8571 (2013).

Tapani Viitala, Niko Granqvist, Susanna Hallila, Manuela Raviña and Marjo Yliperttula: Elucidating the signal responses of multi-parametric surface plasmon resonance living cell sensing: A comparison between optical modeling and drug-MDCKII cell interaction measurements. PlosOne 8. e72192 (2013).

Niko Granqvist, Anders Hanning, Lars Eng, Jussi Tuppurainen and Tapani Viitala: Label-enhanced surface plasmon resonance: a new concept for improved performance in optical biosensor analysis. Sensors 13, pp. 15348-15363 (2013).

Tapani Viitala, Huamin Liang, Mayur Gupta, Thomas Zwinger, Marjo Yliperttula, and Alex Bunker: Fluid dynamics modeling for synchronizing surface plasmon resonance and quartz crystal microbalance as tools for biomolecular studies. J. Colloid Interface Sci. 378, pp. 251−259 (2012).

Klaara Kannisto, Lasse Murtomäki, Tapani Viitala: An impedance QCM study on the partitioning of bioactive compounds in supported phospholipid bilayers. Colloids Surf. B 86, pp. 298-304 (2011).

H. Liang, H. Miranto, N. Granqvist, J.W. Sadowski, T. Viitala, B. Wang*, M. Yliperttula*, Surface Plasmon Resonance Instrument as a Refractometer for Liquids and Ultrathin Films. Sens. Actuator B - Chem. 149, pp. 212-220 (2010).