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2-Photon Lithography for Nanofluidic Lab-on-Chip Devices

Vanderpoorten O, Challa PK, et al. "2-photon lithography for nanofluidic lab-on-chip devices." Biophysical Journal (2018), 144(3):1 689A


The misfolding of proteins inside neuronal cells is known to be linked to neurodegenerative diseases such as Alzheimer's and Parkinson disease. Two promising approaches used by researchers in this field are: The usage of lab-on-chip devices to characterize proteins “in vitro” from a biophysics point of view and fluorescence microscopy to study the protein aggregation in living cells in scaffolds “in vivo”. The length of Amyloid-β 42 (M1-42) aggregates is connected to their toxicity and integrated nanofiltration methods to separate proteins in a microfluidic process pipeline are not available in biological research laboratory without access to expensive electron beam lithography systems as in clean-room facilities. Therefore, we present a novel soft lithography method to produce nanometric structures with two-photon lithography (2PL) for nanofluidic chip fabrication. We demonstrate a system capable of producing master wafers for nanofluidic devices and use these to measure the diffusion of fluorescently labelled Amyloid-β 42 in nanochannels. [1] We also show the fabrication of 3D cell scaffolds for more realistic 3D cell cultures, to improve studies of e.g. the protein Tau in Alzheimer's and its interplay with Amyloid-β 42. [2][3] To accelerate lab-on-chip development we overcome the current microscale fabrication capabilities by combining mask whole-wafer UV-lithography with locally 2P-written nano-sized functional features and make rapid nanofluidic chip prototyping possible.