Til bevillingsoversigt

Novel microfluidic platform for investigation of virus-biofilm interactions

Carlsbergfondets internationaliseringsstipendier

What

This research project aims to establish a physiological in vitro cell model to study the interactions between human herpes viruses (HHVs) and pathogenic bacteria involved in the progression of periodontal disease (PD), and use it to propose new treatment strategies. As a major novelty, we will use a compact platform (tabletop, laptop-sized format), based on centrifugal microfluidics or Lab-on-a-Disc (LoD), for cell culturing in flow (perfusion). The microfluidic disc, where the cells are cultured, has the size and shape of a CD, is compatible with conventional microscopy techniques, and can be combined with a custom-designed, miniaturized microscope for real-time, online monitoring.

Why

PD is the most common chronic inflammatory disease in humans. In PD, bacterial inflammations in the structures supporting the teeth (gingiva, periodontal ligament and alveolar bone) can lead to tooth loss and contribute to systemic inflammation. The disease is difficult to treat with antibiotics, and often complex and expensive surgeries are needed. Traditionally, PD has been ascribed to the overgrowth of pathogenic bacteria, but the bacteria alone do not adequately explain the clinical characteristics of the disease. Recently, HHVs have been suggested as a possible trigger for oral dysbiosis resulting in progression of PD. However, there is an urgent need for in vitro platforms that can facilitate studies of the interactions between bacteria and viruses, to propose new treatments.

How

We will design, optimize and realize a user-friendly, pump- and tubing-free LoD platform to study the cross-talk between HHVs and periodontal bacteria (e.g. Enterococcus faecalis and Streptococcus salivarius). To do so, we will grow virus-infected oral cells under flow in the presence of bacteria, and observe the cellular response by PCR-based detection of viral markers, release of cytokines and oxidative stress. Additionally, we will use the LoD platform to screen the effect of antiviral drugs, with and without co-delivery of antibiotics, as a novel treatment strategy for PD.

SSR

This project will allow us to study viral infections in a physiologically relevant setup. The LoD will be used to study how HHVs interact with pathogenic bacteria, which can vastly improve our understanding of their involvement in oral diseases, and pave the way for future treatments. In a long-term perspective, the platform can be adapted to study any types of cells and viruses. Additionally, the developed LoD platform will provide a more straightforward and cost-effective co-culturing method than what the currently most advanced perfusion setups can offer. A tabletop and easy-to-operate system to study virus-infected cells can bridge the gap to the clinic, where microfluidic systems are still not in practical use despite many years of research in the topic. Controlled co-culturing of cells in perfusion and automated data analysis, combined with the possibility to study viral infections in vitro, will allow for e.g. faster identification of the best treatment strategy and faster diagnostics.