Chip-based nanoscopes offer a stable and affordable peek into the atomic realm

Currently, in order to achieve high-resolution images, optical nanoscopy techniques use glass slides to contain samples along with an advanced microscope for imaging. However, these microscopes are limited, complex and expensive, with some costing as much as EUR 1 million.

The EU funded project NANOSCOPY (High-speed chip-based nanoscopy to discover real-time sub-cellular dynamics) recently announced success with an alternative solution, whereby samples are placed on top of a sophisticated photonic chip and images are then acquired from a standard optical microscope. Here, the chip both holds the sample, like a glass cover slide, and provides a waveguide delivering the required illumination pattern to achieve the super-resolution images.

A nanascope that is both smaller and cheaper

The NANOSCOPY team demonstrated the use of the complex optical chip through two different approaches. Waveguides composed of a material with high refractive-index contrast provided a strong evanescent field that is used for single-molecule switching and fluorescence excitation, thus enabling chip-based single-molecule localisation microscopy. Additionally, multimode interference patterns induced spatial fluorescence intensity variations that enabled fluctuation-based super-resolution imaging.

As chip-based nanoscopy separates the illumination and detection light paths, total-internal-reflection fluorescence excitation is possible over a large field of view, with up to 0.5 mm × 0.5 mm being demonstrated.

Mass producing these photonic chips in factories, in much the same manner as silicon chips, would keep costs down and so encourage widespread adoption. As project team member, Dr Balpreet Singh Ahluwalia, from the Arctic University of Norway has explained, ‘We hope that this advantage will increase the penetration of optical nanoscopy to the developing world. In research environments where resources are limited, most labs are equipped with low-quality optical microscopes because the upfront costs of nanoscopes are prohibitive.’

Looking to the future

Summarising the advantages of the new technology, Dr Ahluwalia added, ‘Besides being more compact, stable and affordable, our chip-based nanoscope also captures images over extremely large fields of view. It can acquire super-resolved images from a field of view 100 times larger than what can be presently achieved using commercial optical nanoscopy systems.’

These advantages have implications for a number of medical fields, notably pathology, where an optical microscope would typically scan an area of 50 microns at a time, taking days to scan an entire sample of tissue, blood or urine with surface areas of several square millimetres.

The team is currently working with liver cells to better understand how filtration works. This wasn’t possible previously as the specialised cells contain nanoholes, which being only around 50-200 nanometres wide, can’t be seen with a normal microscope.

In the quest to retrofit as many standard optical microscopes as possible with their photonic chip, the project is currently in contact with possible manufacturers. As Dr Ahluwalia summarised, ‘Our business case is strong. Imagine a coffee machine – the customer only needs to replace the coffee, which is much cheaper than buying a brand new machine every time you fancy an espresso.’

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