Label-free single molecule detection and mass spectrometry using an inverted optical microscope

Interferometric Scattering Microscopy (iSCAT) is by far the most sensitive label-free single molecule biosensing technique currently available to the research community. The technique offers single molecule sensitivity without the use of any labels or reporter molecules with increasing application of biomolecular interaction analysis in drug discovery. However, widespread adoption of this technique in the pharma/biotech industries and research facilities has been limited owing to the expensive and complex experimental setups involved.

Oxford researchers have developed a simple, inexpensive, and accessible implementation of iSCAT, which addresses the disadvantages restraining the fast growth of label-free single molecule detection and mass spectrometry. The miniaturisation of the microscope offers improved performance and opens up the use of iSCAT to a substantial global market and user-base.


Interferometric Scattering Microscopy (iSCAT) represents a powerful approach to both single-particle tracking with unique spatiotemporal resolution and label-free sensitivity at the single-molecule level. Such techniques are used to study a variety of important processes in the life sciences and condensed matter physics and are highly promising as drug discovery tools in the pharmaceutical & biotechnology industry. The application of iSCAT offers far greater sensitivity and time-resolution than other current techniques. iSCAT is the most sensitive label-free single molecule biosensor in the world.

However, the widespread adoption of iSCAT has been hindered by the associated experimental complexity requiring large optical tables, custom-built optical microscopes, unconventional cameras, and complex sample illumination. These costly requirements have placed the use of iSCAT beyond the means of the majority of research facilities.

A Simple, accessible implementation

Oxford researchers have developed a simple implementation that will enable widespread, low-cost adoption of iSCAT, opening up a substantial global market. A unique combination of concepts has enabled the design of iSCAT microscopes to be simplified dramatically, achieving identical sensitivity to the more complex and expensive state of the art.

Benefits of the Oxford design include:

  • No requirement for an optical table or complex optics/electronics
  • Simple operation
  • Use of low-cost imaging cameras
  • No loss of imaging performance or sensitivity
  • No requirement for complex scanning arrangements

This development has the potential to revolutionise label-free, single-molecule imaging, with widespread implications for the pharmaceutical & biotechnology industry and the associated global research community. Applications include use as a drug discovery tool for hit confirmation and lead generation, and for the study of biomolecular interactions such as protein aggregation. Our initial results demonstrate the observation of single proteins in solution without labels and determination of the molecular weight and thereby the status of protein aggregation.


This technology is the subject of a patent application. Substantial proof of concept experiments have been conducted and prototyping is in progress. Oxford University Innovation is seeking external partners to support the commercialisation of this emerging technology.

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