Imec Demonstrates Direct Optical Reading of Single-Molecule DNA Bases in Modified Nanopores

Results on unique combination of surface enhanced Raman spectroscopy and nanopore fluidics published in Nature Communications

DNA strands in nanopores
Sub-10nm Nanoslit

In a Nature Communications paper published this week (https://rdcu.be/MYO6), imec, the world-leading research and innovation hub in nano-electronics and digital technology, describes a new concept for direct identification of single DNA bases. The technique has the potential to detect, with an unprecedented spatial resolution and without any labeling, the genetic code, as well as epigenetic variations in DNA. The combination of nanopore fluidics and surface enhanced Raman spectroscopy makes it a unique concept and a very promising tool for evolutionary biologists and for research on disease development.

Today, direct, real-time identification of nucleobases in DNA strands in nanopores is limited by the sensitivity and the spatial resolution of established ionic sensing strategies. In addition, established DNA sequencing techniques often use fluorescent labeling which is costly and time-consuming. In its Nature Communications paper, imec demonstrated a promising alternative based on optical spectroscopy, with no need for labeling and with the unique ability to identify nucleobases, individually, and incorporated in a DNA strand. The technique is based on nanofluidics to drive the DNA strand through an engineered plasmonic nanoslit, and surface enhanced Raman spectroscopy to make a ‘fingerprint’ of the adsorbed nucleobases up to the level of molecular bonds. The spectroscopic signal is enhanced both by a gold coating on top of the nanoslit, and the engineered shape of the nanoslit.

“The result reported here is an important step towards a solution for fast and direct sequencing up to the epigenetic level,” stated and Chang Chen, senior researcher at imec.

The signal generated by Raman spectroscopy holds a lot of information about the molecules and the molecular bonds. Not only can the DNA code be ‘read’, but also base modifications such as methylation, histone acetylation, and microRNA modification, which carry more detailed information about epigenetic variations. Such variations are important for evolutionary studies as they influence gene expression in cells. Moreover, they have been shown to impact the origin and development of diseases such as cancer.

“We leverage our world-class expertise in chip design and 300 mm Si wafer manufacturing technology and bio-lab facilities to develop tailored solutions for the life sciences industry,” stated Pol Van Dorpe, principal member of technical staff. “The solution we describe here is only one example of the technologies we are working on. Our toolbox includes knowledge on nanopores, spectroscopy, photonics, single-molecule detection and nanofluidics which we use in developing next-generation solutions for our industry partners in genomics and diagnostics.”

About imec

Imec is the world-leading research and innovation hub in nano-electronics, energy and digital technologies. The combination of our widely acclaimed leadership in microchip technology and profound software and ICT expertise is what makes us unique. By leveraging our world-class infrastructure and local and global ecosystem of partners across a multitude of industries, we create groundbreaking innovation in application domains such as healthcare, smart cities and mobility, logistics and manufacturing, and energy.

As a trusted partner for companies, start-ups and universities we bring together close to 4,000 brilliant minds from over 85 nationalities. Imec is headquartered in Leuven, Belgium and also has distributed R&D groups at a number of Flemish universities, in the Netherlands, Taiwan, USA, China, and offices in India and Japan. In 2017, imec’s revenue (P&L) totaled 546 million euro. Further information on imec can be found at www.imec-int.com.

Imec is a registered trademark for the activities of IMEC International (a legal entity set up under Belgian law as a “stichting van openbaar nut”), imec Belgium (IMEC vzw supported by the Flemish Government), imec the Netherlands (Stichting IMEC Nederland, part of Holst Centre which is supported by the Dutch Government), imec Taiwan (IMEC Taiwan Co.) and imec China (IMEC Microelectronics (Shanghai) Co. Ltd.) and imec India (Imec India Private Limited), imec Florida (IMEC USA nanoelectronics design center).

Source : Imec