Editorial Article: Intricate Nanofabrication Aids Optical Mapping of DNA

Find out how Professor Robert Blick, University of Hamburg, fabricates nanochannels to optically map DNA

24 Oct 2017

Image © 123rf.com
Dr. Robert Blick, Director of the Center for Hybrid Nanostructures at the University of Hamburg, Germany

Optical mapping of DNA, utilized in the end stages of genome sequencing projects, involves a single molecule of DNA being drawn through a nanochannel and elongating to monitor the dynamic processes along the strand of DNA. In the past, optical mapping has been limited to use on genomic sub-fragments rather than on full lengths of DNA from whole chromosomes. 

In order to utilize optical mapping for sequencing DNA, it’s imperative to have the appropriate nanofluidic devices, i.e. nanochannels to elongate the desired sample. In this SelectScience® article, we look at the work of Dr. Robert Blick, Director of the Center for Hybrid Nanostructures at the University of Hamburg, whose team, Dr. Irene Fernandez-Cuesta (postdoc) and graduate student Ms Parisa Bayat, works at the junction of nanoscience and nanostructure physics.


Optical mapping of DNA

A nanofluidic channel master stamp developed by Dr. Blick’s group and imaged using ZEISS Crossbeam 550 focused ion beam scanning electron microscope.

Blick’s focus has been to fabricate multi-level nanodevices to facilitate an ultra-high throughput DNA optical mapping. His team recently published a paper proposing a rapid prototyping method to construct nanofluidic devices specifically for DNA optical mapping. The authors made a hard silicon stamp using a focused ion beam (FIB), and then used this stamp for molding a polymer by UV-nanoimprint lithography. Direct milling by FIB allowed the definition of 3D structures with multiple lateral sizes and depths in a single step. It was possible to easily characterize the imprinted devices in the scanning electron microscope (SEM), even without coating them using charge neutralization techniques.

To design robust nanochannels for DNA mapping, Blick’s team uses ZEISS Crossbeam 550, an integrated focussed ion beam scanning electron microscope (FIB-SEM), enabling the investigation of nanostructures, and coupling it with analytical and imaging methods. “ZEISS Crossbeam 550 is fundamentally important, since we are using it for nanofabrication as well as structural analysis,” comments Blick.

 As Blick’s team configured a fast and flexible prototype, they were able to fabricate and test different channel sizes and configurations. For example, they were able to characterize meander-shaped nanochannels which helped visualize long molecules in a single microscopy frame. 

Meander-shaped nanochannels fabricated and characterized by Dr.  Blick’s team using using ZEISS Crossbeam 550

The future of nanotechnology

The future of Blick’s research will involve delving into nano-bio-electronics, a rapidly expanding field that offers to bridge the gap between nanofabrication and living cells. Nanotechnology provides the tools to observe biological structures and phenomena at their natural ‘nano’ scale, potentially leading to drastic increases in sensitivity and biocompatibility. This field has great potential to answer questions in fundamental biology and, when translated, in healthcare as well.

Learn more about ZEISS Crossbeam 550

Download application note: ZEISS Crossbeam - Enabling Smart FIB Work with SmartSEM

Download application note: ZEISS Focused Ion Beam Column - Enabling Precision and Long-term Stability for Cutting Edge Crossbeam Applications

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