Method and apparatus for detecting particles, like biological macromolecules or nanoparticles
Inventors
Sandoghdar, Vahid • Piliarik, Marek • KOENIG, Katharina
Assignees
Max Planck Gesellschaft Zuf Foerderung Der Wissenschaften E V • Max-Planck-Gesellschaft zur Förderung der Wissenschaften eV
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Publication Number
US-12607599-B2
Publication Date
2026-04-21
Expiration Date
Abstract
A method of detecting particles, e. g. proteins, after separation of particles based on their specific features, e.g. charge, size, shape, density, as series of single light scattering events created by the individual particles is described. The particles are separated from each other along the separation path and particles have specific arrival times at the target side depending on the particle features. The detecting step comprises an interferometric sensing of the light scattered at individual particles bound or transient in the detection volume. Parameters of the scattering light signals e.g. the interferometric contrast are analyzed for obtaining specific particle features, e.g. size, mass, shape, charge, or affinity of the particles. Furthermore, a detection apparatus being configured for detecting particles is described.
Core Innovation
The invention relates to a detection apparatus for detecting particles by combining a separation device with interferometric scattering detection (iSCAT). Particles are moved along a separation path from a source side in a sample container toward a target side in a target container using a separation force generator, and the target container includes a detection volume with an opening end of the separation path located in the target container for optical interrogation.
The detection device uses an illumination light source and an optical system configured as a common-path interferometer. A reflecting detection surface is arranged at a fixed distance from the opening end and restricts the detection volume, and the imaging optics direct illumination light to the detection volume and output light collected from the reflecting detection surface in reflection to a sensor camera. The output light comprises light scattered from particles in the detection volume and illuminating light reflected from the reflecting detection surface, enabling interferometric signals derived from their superposition.
An analyzing unit coupled to the detection device analyzes the detected output light to obtain specific particle features. The apparatus is configured to extract particle size, mass, shape, charge, and affinity, with the separation delivering time-resolved information through arrival times from different particles along the separation path. Two operational regimes are described: particles bound or transiently bound on the reflecting surface producing time-resolved series of single scattering events, and inline detection where transient particles traverse a restricted detection volume in a nanofluidic or nanocapillary detection volume with interferometric tracking and correlation or lock-in processing.
Claims Coverage
Independent claim clm-00001 defines a detection apparatus with three inventive features: a separation device that moves particles into a restricted detection volume, a common-path interferometer with a fixed reflecting detection surface, and analysis of interferometric output light to obtain specific particle features. Dependent claims further refine separation-force generation, optical focal operation, and time-resolved, type-selective separation with detection of single light scattering events.
Separation path with separation force generator into restricted detection volume
A separation device having a separation path and a separation force generator arranged to create a separation force along the separation path for moving particles toward a target side, wherein the target container includes a detection volume and the separation path has an opening end located in the target container.
Common-path interferometer using reflecting detection surface and sensor camera
A detection device configured for detecting the particles in the detection volume, including an illumination light source for providing illumination light; a reflecting detection surface arranged with a fixed distance from the opening end and restricting the detection volume; a sensor camera; and an optical system with imaging optics arranged as a common-path interferometer for directing illuminating light to the detection volume and the reflecting detection surface and collecting output light from the reflecting detection surface in reflection, wherein the output light comprises both light scattered from the particles and illuminating light reflected from the reflecting detection surface and the optical system directs the output light to the sensor camera.
Analyzing output light to obtain specific particle features
An analyzing unit coupled with the detection device and including a computer configured for analyzing the output light detected by the detection device and obtaining specific particle features of the particles based on analyzing the output light.
Reflecting detection surface arranged for binding particles
A detection apparatus wherein the reflecting detection surface is arranged to bind the particles to be detected.
Tapered opening end positioned out of illumination focus to control diffusion versus separation force
A detection apparatus configured such that the separation path has a tapered opening end located in the target container facing a reflecting detection surface, with positioning such that the opening end is located out of a focus of the illumination light source, and with control of diffusion versus separation-force effects.
Electrode-based separation force generator with separation-voltage modulation
A detection apparatus wherein the separation force generator includes two electrodes connected to a separation-voltage source that modulates the separation voltage to modulate the separation force.
Interferometric signal collection at at least one focus position using background reference superposition
A detection apparatus wherein the detection device illuminates at least one focus position in a detection volume and collects interferometric light signals at that focus position as a superposition of a background reference portion and a scattered portion created by the particles.
Type-selective separation with arrival-time determination and detection as series of single light scattering events
A detection apparatus using the separation force generator to individually separate particles of one particle type from other particle types and remaining sample components along the separation path, determining arrival times from different particle velocities, and detecting the individually separated particles as a sequence of single light-scattering events using interferometric sensing by collecting the scattering light signals.
The claim set covers a detection apparatus that moves particles through a separation path into a restricted detection volume and detects them using a common-path interferometer formed by illumination and a fixed reflecting detection surface. The analyzing unit extracts specific particle features from the interferometric output light, while dependent refinements specify binding on the reflecting surface, optical focusing geometry, electrode-based separation-force modulation, and type-selective separation combined with arrival-time-based, time-resolved detection of single light scattering events.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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