Methods and apparatus for monitoring interactions between particles and molecules using nanophotonic trapping

A label-free method for characterizing an interaction between a first unlabeled biomolecular particle and a second unlabeled biomolecular particle, the method comprising the steps of:

• providing an optical trap system, the optical trap system comprising a photonic crystal resonator having a light source directed thereto for exciting the photonic crystal resonator and a camera positioned above a trapping site in the photonic crystal resonator;
• radiating light from the light source in proximity of the trapping site in the photonic crystal resonator;
• optically trapping the first unlabeled biomolecular particle with a first known refractive index in the photonic crystal resonator using light with a specific minimum power from the light source to induce trapping;
• wherein the first unlabeled biomolecular particle has a known radius, R0;
• obtaining a first measurement of Brownian motion while the first unlabeled biomolecular particle is in the photonic crystal resonator based on light scattering captured by the camera from the first unlabeled biomolecular particle;
• introducing the second unlabeled biomolecular particle with a second known refractive index into the photonic crystal resonator;
• incubating the first and second unlabeled biomolecular particle under conditions suitable for binding said first and second unlabeled biomolecular particle to form a complex, wherein the second unlabeled biomolecular particle has a potential affinity for the first unlabeled biomolecular particle;
• wherein the the first unlabeled particle has a second radius, R′ and R′−R0=ΔR;
• optically trapping the first unlabeled biomolecular particle in the photonic crystal resonator using light with the specific minimum power from the light source to induce trapping after incubation;
• wherein the first unlabeled biomolecular particle is a virus and the second unlabeled biomolecular particle is an antibody;
• obtaining a second measurement of Brownian motion of the first unlabeled particle in the photonic crystal resonator after incubation based on light scattering captured by the camera from the first unlabeled biomolecular particle;
• obtaining a relative Brownian motion measurement, defined as a comparison of the first and second measurements of Brownian motion, of the first unlabeled particle after incubation and based on light scattered by the first unlabeled particle captured by the camera;
• analyzing a relationship between the relative Brownian motion measurement of the first unlabeled particle after incubation and ΔR;
• and
• determining, using the relationship of the relative Brownian motion measurement of the first unlabeled particle with respect to ΔR, a Brownian motion measurement of the photonic crystal resonator;
• wherein said relationship provides indication whether a complex is formed.