Single-Molecule Sensing

In 2014, we built the world’s most sensitive optical device capable of detecting single-molecules without chemical alteration (1). The platform is based on optical microcavities, approximately 100 um diameter glass microspheres that are used as optical sensors. Optical resonances, so-called Whispering gallery modes (WGMs), were excited in the microspheres for the label-free detection of biomolecules (2, 3). These microsphere sensors were used to detect single DNA molecules and their interaction kinetics (1).

In 2015-2016, we further advanced these optical sensors, improved upon the detection limit and time resolution. Advanced experimental capabilities of these sensors led to the publication of seminal works, on the sensing of single atomic ions in solution (4), the detection of various single-molecule surface reactions from low to high affinity (5), and on unprecedented nanosecond time resolution for label-free single-molecule studies(6). These demonstrations consolidate our optical technique as one of the most sensitive tools for label-free single molecule studies. They establish a biosensor technology that can detect and analyse the intricate dynamics of single biomolecules. In most recent works we demonstrate such capability, with the first label-free optical technique capable of observing enzymatic interactions and associated conformational changes on the single molecule level (7).

The future of our micro-optical sensors is outlined in a recent roadmap (8). To summarize, our optical sensors can help us understand how our bodies work at the nanoscale, where individual biomolecules such as enzymes take on the role of nano-machines, and where parts of a protein move similar to the pistons of an engine. Without the need of a label, our sensors will provide a universal tool for the unabated exploration of structural dynamics and shape-changes in individual proteins. Our optical devices can furthermore harness the extreme speed, selectivity and specificity of the biological nanoworld. With further technological advances already in the pipeline, our sensors will benchmark nanoscale metrology. Those with ultimate sensitivity will provide a tool for uncovering novel physical phenoma at the nanoscale.

In a second line of experiments, we have established experiments with two-dimensional photonic crystal structures. These structures can provide optical sensing devices that are highly suitable for on-chip biosensing applications. In photonic crystals, light is confined in engineered defect cavities or by means of Anderson Localization - as we have uncovered in our previous research. Recently, we have focused on establishing a photonic crystal biosensing platform by leveraging Anderson Localization and free-space coupling with polarization-tailored beams. With such a platform, we realise various on-chip single-molecule biosensing applications.