Browsing by Subject "microfabrication"

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  • Kiiski, Iiro; Ollikainen, Elisa; Artes, Sanna; Järvinen, Päivi; Jokinen, Ville; Sikanen, Tiina (2021)
    UDP-glucuronosyltransferases (UGTs), located in the endoplasmic reticulum of liver cells, are an important family of enzymes, responsible for the biotransformation of several endogenous and exogenous chemicals, including therapeutic drugs. However, the phenomenon of 'latency', i.e., full UGT activity revealed by disruption of the microsomal membrane, poses substantial challenges for predicting drug clearance based on in vitro glucuronidation assays. This work introduces a microfluidic reactor design comprising immobilized human liver microsomes to facilitate the study of UGT-mediated drug clearance under flow-through conditions. The performance of the microreactor is characterized using glucuronidation of 8-hydroxyquinoline (via multiple UGTs) and zidovudine (via UGT2B7) as the model reactions. With the help of alamethicin and albumin effects, we show that conducting UGT metabolism assays under flow conditions facilitates in-depth mechanistic studies, which may also shed light on UGT latency.
  • Sikanen, Tiina; Kiiski, Iiro; Ollikainen, Elisa (John Wiley & Sons Ltd., 2021)
    Advances in Pharmaceutical Technology
    This chapter reviews the evolution of microfabrication methods and materials, applicable to manufacturing of micro total analysis systems (or lab‐on‐a‐chip), from a general perspective. It discusses the possibilities and limitations associated with microfluidic cell culturing, or so called organ‐on‐a‐chip technology, together with selected examples of their exploitation to characterization of pharmaceutical nano‐ and microsystems. Materials selection plays a pivotal role in terms of ensuring the cell adhesion and viability as well as defining the prevailing culture conditions inside the microfluidic channels. The chapter focuses on the hepatic safety assessment of nanoparticles and gives an overview of the development of microfluidic immobilized enzyme reactors that could facilitate examination of the hepatic effects of nanomedicines under physiologically relevant conditions. It also provides an overview of the future prospects regarding system‐level integration possibilities facilitated by microfabrication of miniaturized separation and sample preparation systems as integral parts of microfluidic in vitro models.
  • Tatikonda, Anand; Jokinen, Ville P.; Evard, Hanno; Franssila, Sami (2018)
    The low fabrication cost of SU-8-based devices has opened the fields of point-of-care devices (POC), mu TAS and Lab-on-Chip technologies, which call for cheap and disposable devices. Often this translates to free-standing, suspended devices and a reusable carrier wafer. This necessitates a sacrificial layer to release the devices from the substrates. Both inorganic (metals and oxides) and organic materials (polymers) have been used as sacrificial materials, but they fall short for fabrication and releasing multilayer SU-8 devices. We propose photoresist AZ 15nXT (MicroChemicals GmbH, Ulm, Germany) to be used as a sacrificial layer. AZ 15nXT is stable during SU-8 processing, making it suitable for fabricating free-standing multilayer devices. We show two methods for cross-linking AZ 15nXT for stable sacrificial layers and three routes for sacrificial release of the multilayer SU-8 devices. We demonstrate the capability of our release processes by fabrication of a three-layer free-standing microfluidic electrospray ionization (ESI) chip and a free-standing multilayer device with electrodes in a microchannel.