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.
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).
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).