Harvard University has launched a new start-up company, Ultivue, which aims to commercialise a group of imaging reagents that provide standard microscopes with super resolution capabilities. The technology will allow scientists to reach resolutions that could previously only be achieved using expensive specialised instruments.
Using standard fluorescent microscopes, molecular objects that are closer together than 200nm cannot be distinguished from each other and instead appear as single blurry spots. Super-resolution microscopes have been developed to overcome this optical barrier, but their high cost can be prohibitive, and they often rely on specialised conditions and fluorescent dyes that are turned on and off with the help of a laser.
However, the DNA-Paint and Exchange-Paint technologies developed by Harvard University’s Wyss Institute for Biologically Inspired Engineering can be used to surpass the resolving power of current super-resolution techniques but on standard fluorescent microscopes.
‘DNA-Paint and Exchange-Paint technology distinguishes molecules at super-high resolution and allows researchers to visualise a large number of species at the same time using low cost reagents, simultaneously overcoming two central limitations in conventional microscopic imaging today,’ said Peng Yin, a Core Faculty member at the Wyss Institute and an associate Professor of Systems Biology at Harvard Medical School.
‘We can now study many processes at a molecular level such as changes in chromosomes or minuscule neuronal structures. We also could determine molecular states of diseases in a more comprehensive fashion and with much greater detail, providing an enabling platform for digital pathology,' said Yin. Digital pathology is a growing computer-based trend in medicine aiming to achieve faster, cheaper and more accurate disease diagnostics.
To accomplish this, DNA-Paint leverages the physical properties of DNA. The key principle is based on the tunable association of two short complementary DNA strands – one is attached to the object to be visualised and the other to a fluorescent dye.
By carefully designing the nucleotide sequence of the complementary DNA strands, the time the two DNA strands remain bound before being separated again can be programmed precisely. This transient DNA interaction typically results in 'blinking' of the fluorescent dye with targets being localised by the dye with much higher precision than would be possible by other means. By using different DNA sequences to label distinct targets, and applying the imager strands one target at a time, many distinct targets can be imaged sequentially using only one dye and one laser source. This so-called Exchange-Paint variation lends itself to multiplexing that can visualise 10 and potentially up to 100 different molecular species.
Since its initial development, Yin and his co-workers have increased the resolution of the DNA-Paint technology and added key capabilities to their platform including multiplexing and compatibility with antibodies, which are broadly used target-specific reagents. The team also engaged with academic partners to test and de-risk a beta version of the future reagent kit on various biological samples.
Ultivue will use super-resolution DNA-Paint and Exchange-Paint as its defining technologies to develop and expand a portfolio of multiplexed super-resolution-enabling and enhancing products.
‘The launch of Ultivue is a testament to the Wyss Institute's ability to launch bio-inspired technologies out of the lab and into the commercial marketplace, in this instance by leveraging recent advances in DNA nanotechnology to create a low-cost alternative to super-resolution microscopy that could bring this invaluable new capability into virtually any research or clinical laboratory,’ said Wyss Institute founding director Dr Don Ingber.
Super-resolution microscopy with a lighter touch: Andy Extance discusses how scientific institutions and super-resolution companies are tackling the challenge photobleaching n super resolution microscopy