Special Bioengineering Seminar

I will discuss my research on engineering DNA probes for super-resolution bioimaging using tools and concepts from DNA nanotechnology.  We have recently developed DNA-PAINT, an imaging method that can be used for super-resolution fluorescence imaging with a resolution of currently up to 10 nm. DNA-PAINT exploits transient binding of fluorescently labeled oligonucleotides to their targets to obtain stochastic switching between fluorescence ON- and OFF-states, thus enabling specific, programmable and modular super-resolution imaging which is easy to implement and use. Unlike existing techniques that rely on the externally controlled blinking of special fluorophores, our technique utilizes programmable autonomous blinking of a nucleic acid probe.  DNA is also widely used for programmable construction of two- and three-dimensional nanostructures such as in DNA origami. By combining the power of DNA nanostructures for arranging molecules on the nanoscale with the sub-diffraction imaging capabilities of DNA-PAINT, we have demonstrated geometrically encoded super-resolution fluorescent barcodes for multiplexed single-molecule imaging. We have also recently extended DNA-PAINT for highly multiplexed 3D imaging in a cellular environment. DNA-PAINT's unprecedented molecular control on the blinking behavior of the imaging probe promises high multiplexing power and ultra-resolution. Unlike current super-resolution methods, our programmable blinking technique only requires standard instrumentation and is widely applicable. This will bring the performance, usability, and applicability of super-resolution imaging to a new level, and help transform research practice in diverse biomedical fie