Biosensor for monocyte activity testing

PhD project Matthias Irmscher

Master student: Karel van Laarhoven

Circulating monocytes have been identified as key components in the development of atherosclerotic lesions. At the onset of the disease, the cells of the endothelium are locally activated. This initial step can be triggered by a multitude of factors of which an elevated level of LDL (low-density lipoprotein, or colloquially known as “bad cholesterol”) is thought to be the preeminent one. Once activated, the affected endothelial cells begin to express increased levels of surface proteins like ICAM-1 (inter-cellular adhesion molecule 1) and MCP-1 (monocyte chemotactic protein 1). As a result, circulating monocytes are activated and begin to adhere to the endothelium to subsequently migrate into the underlying tissue where they ultimately differentiate into macrophages. Since the activation of monocytes takes place in circulation, an elevated proportion of activated monocytes in a blood sample is believed to be indicative of atherosclerosis.

One way to determine the activation of monocytes is by measuring the expression levels of specific membrane-bound proteins, e.g. integrin αMβ2 (CD11b). Such measurements are currently carried out with the help of flow cytometers whose availability is limited to research laboratories and which have to be operated by skilled personnel. We are investigating technologies for the future development of an integrated biosensor that is capable of rapid and accurate testing of small blood samples. Our studies focus on the use of functionalized superparamagnetic particles, because such particles can serve both as detection labels and as media for the manipulation and transport of cells in an integrated device.

This PhD project is a collaborative effort of the MBx group at Eindhoven University, the University Medical Center Utrecht, the Academic Hospital Maastricht, Future Diagnostics, and Philips Research. Funding is provided through the Circulating Cells project in the Center for Translational Molecular Medicine (CTMM, www.ctmm.nl).