Key project: Immobilized enzyme microreactors

Microfluidic tools for understanding the impacts of human drug metabolism on the environmental health

The project aims at introducing new high-throughput and automated technology for drug  metabolism research. The high-throughput is achieved by implementing microfluidic immobilized enzyme microreactors (IMERs) in a parallel manner using modern microfabrication methods and advanced functional(ized) materials.

Another important aim of the project is to introduce new operational models to environmental research, particularly to screening of pharmaceutical residues in waste water and sludge by taking into account the role of the biological metabolites of drugs in the total environmental load posed by active pharmaceutical ingredients (APIs). The impact of the APIs’ biological metabolites on environmental health is presently almost entirely overlooked, when assessing the environmental risk quotient of an API, even if metabolites are in many cases the predominant form of the residual APIs excreted in urine and entering the municipal waste water treatment plants. This is mainly because of a major technical limitation: the metabolite standards required for analytical method develop and quantitative screening of the residue levels are either completely lacking or only available in limited cases at unreasonably high price.

The project addresses the above mentioned needs by utilising enzyme immobilization protocols and microfluidic technology to harness the IMERs for not only environmental monitoring, but also for the needs of drug discovery and waste water purification, by optimizing the throughput of the metabolite production to meet the sufficient yield, while
maintaining reasonable correlation in terms of affinity (Km) and isoenzyme specificity to the prevailing in vitro methodologies and in vivo data.

Three different microfluidic platforms are being developed in parallel, namely paper-based lateral flow assays, droplet-based digital microfluidic assays, and continuous flow microreactors. A pilot study on the existence and role of metabolites of selected APIs is also being carried out in order to assess the share of the metabolites in the total
environmental load posed by the API in question.

 

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This project has received funding from the Academy of Finland’s key project funding scheme “Forging ahead with Research” under grant agreement no. 304400.