Arago Biosciences is the latest spinout company to be created from research produced by the Department of Chemistry. Based on the work from the Kukura and Benesch groups, the novel technique that Arago utilises allows the detection, imaging and accurate mass determination of single biomolecules in solution. The company’s innovative technology can perform analysis on molecules without using any labels or matrices, through the use of small instruments that are close to a shoebox in size.
Essentially all optical single molecule techniques rely on fluorescence, which involves the emission of light from a molecule after being excited by electromagnetic radiation. Not all molecules are fluorescent, however, so recent efforts have concentrated on the development of more universally applicable methods.
The newly developed technique, interferometric scattering mass spectrometry (iSCAMS), is an optimised form of light microscopy whereby the light scattered by a single protein can be measured. It works on the basis that proteins are all made up of the same subunits (amino acids), which are all roughly of the density, have similar masses and scatter light by a similar amount. A protein with twice as many amino acids will therefore scatter roughly twice as much light; through this technique it is possible to measure the mass of single protein molecules to within 2% of their true masses.
“The scattering signal observed is proportional to the polarisability of the molecule and therefore the number of amino acids present,” Professor Kukura explains. “The greater the number of amino acids present in the protein, the greater the scattering of light observed.”
This technique has thus far been used to image and determine the mass of a range of biomolecules weighing between 50 and 800 kDa, including polypeptides, glycosylated proteins and lipoproteins. iSCAMS also allows molecular dynamics to be observed, such as how two protein units join together.
The approach has the potential to revolutionise the characterisation of molecular interactions, making it of particular interest to the pharmaceutical, biomedical and research sectors. For example, iSCAMS has been used to detect the aggregation of alpha-synuclein, which is associated with Parkinson’s disease. The mass of the protein is 14 kDa, which increases to hundreds of kDa as aggregated structures form.
Another application of the technology is in drug screening, which could be used to deduce how many drug molecules bind to a particular target. The creation of the new spinout company will enable this imaging technology to be made available to a wide range of businesses and researchers.