The interaction of electromagnetic waves with matter can be controlled by structuring the matter on the scale of the wavelength of light, and various photonic components have been made by structuring materials using top-down or bottom-up approaches. Dip-pen nanolithography is a scanning-probe-based fabrication technique that can be used to deposit materials on surfaces with high resolution and, when carried out in parallel, with high throughput. Here, we show that lyotropic optical diffraction gratings--composed of biofunctional lipid multilayers with controllable heights between approximately 5 and 100 nm--can be fabricated by lipid dip-pen nanolithography. Multiple materials can be simultaneously written into arbitrary patterns on pre-structured surfaces to generate complex structures and devices, allowing nanostructures to be interfaced by combinations of top-down and bottom-up fabrication methods. We also show that fluid and biocompatible lipid multilayer gratings allow label-free and specific detection of lipid-protein interactions in solution. This biosensing capability takes advantage of the adhesion properties of the phospholipid superstructures and the changes in the size and shape of the grating elements that take place in response to analyte binding.
Molecular patterning processes taking place in biological systems are challenging to study in vivo because of their dynamic behavior, subcellular size, and high degree of complexity. In vitro patterning of biomolecules using nanolithography allows simplification of the processes and detailed study of the dynamic interactions. Parallel dip-pen nanolithography (DPN) is uniquely capable of integrating functional biomolecules on subcellular length scales due to its constructive nature, high resolution, and high throughput. Phospholipids are particularly well suited as inks for DPN since a variety of different functional lipids can be readily patterned in parallel. Here DPN is used to spatially pattern multicomponent micro- and nanostructured supported lipid membranes and multilayers that are fluid and contain various amounts of biotin and/or nitrilotriacetic acid functional groups. The patterns are characterized by fluorescence microscopy and photoemission electron microscopy. Selective adsorption of functionalized or recombinant proteins based on streptavidin or histidine-tag coupling enables the semisynthetic fabrication of model peripheral membrane bound proteins. The biomimetic membrane patterns formed in this way are then used as substrates for cell culture, as demonstrated by the selective adhesion and activation of T-cells.
There is a strong need for low-cost biosensors to enable rapid, on-site analysis of biological, biomedical, or chemical substances. We propose a platform for label-free optical biosensors based on applying the analyte onto a surface-functionalized photonic crystal slab and performing a transmission measurement with two crossed polarization filters. This dark-field approach allows for efficient background suppression as only the photonic crystal guided-mode resonances interacting with the functionalized surface experience significant polarization rotation. We present a compact biosensor demonstrator using a low-cost light emitting diode and a simple photodiode capable of detecting the binding kinetics of a 2.5 nM solution of the protein streptavidin on a biotin-functionalized photonic crystal surface.
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