The reliable characterization of heterogeneous cell populations is a central prerequisite in many areas of medicine, biology, and biotechnology. Conventional techniques used for this purpose are either high-throughput, such as fluorescence-activated cell sorting (FACS), but limited to a small number of parameters or high-content, such as slide-based imaging approaches, which require surface attachment and preclude cell sorting. It is the overall objective of this proposal to develop a multimodal, microfluidic, laser trap-assisted cell screening platform technology – µFLAX – for the contact-free manipulation and high-content screening of suspended cells with high-throughput. Our approach is especially designed for blood cells, which will be serially trapped from microfluidic flow with a dual-beam trap. In addition to the extraction of molecular information (similar to FACS), we also incorporate mechanical phenotyping as a powerful new functional cell marker. In addition to looking, we can feel for functional changes using optically induced forces. This will be further augmented by structural analysis using digital holographic microscopy, cell size analysis using an optical cell rotator, and biological stimulation by microfluidic delivery of biochemical agents. This combination will offer much higher sensitivity and specificity in determining functional states compared to currently available techniques. And since the cells are suspended they can be sorted and analyzed further, which will aid potential molecular target identification. Once developed, we will demonstrate the applicability of µFLAX for the investigation and diagnosis of inflammation and infection. Based on our track record in pioneering innovative physical solutions to biomedical problems we anticipate that through this project we will provide novel insight into system biological aspects of these disorders on the single-cell level, as well as novel diagnostic and therapeutic options.
Call for proposal
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