Flow cytometry system and method
Inventors
Schreuder, Frederik • Hoekman, Marcel • Dekker, Ronald • Hosseini, Seyed Naser
Assignees
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Publication Number
US-10180390-B2
Publication Date
2019-01-15
Expiration Date
Abstract
A flow cytometry system having a flow channel defined through the thickness of a substrate is disclosed. Fluid flowing through the flow channel is illuminated by a first plurality of surface waveguides that are arranged around the flow channel in a first plane, while a second plurality of surface waveguides arranged around the flow channel in a second plane receive light after it has interacted with the fluid. The illumination pattern provided to the fluid is controlled by controlling the phase of the light in the first plurality of surface waveguides. As a result, the fluid is illuminated with light that is uniform and has a low coefficient of variation, improving the ability to distinguish and quantify characteristics of the fluid, such as cell count, DNA content, and the like.
Core Innovation
The disclosed invention relates to a flow cytometry optofluidic system in which a substrate monolithically integrates a flow channel with optically coupled surface waveguides. The substrate defines a first plane and includes a flow channel operative for conveying fluid along a first direction that is substantially orthogonal to the first plane, with the flow channel located within a first region of the substrate.
The system includes a first surface waveguide and a second surface waveguide, each located in respective planes that are substantially parallel to the first plane, with the second plane between the first plane and a third plane. Optical coupling between the surface waveguides and the flow channel enables interrogation of the fluid with an illumination pattern based on light signals emitted from the surface waveguides.
The waveguide sets are arranged around a detection zone/flow channel, including configurations in which waveguides are coplanar in first and second planes that are substantially parallel to the major surfaces of the substrate. Polygonal arrangements about the flow channel are described, where the polygonal arrangement has a plurality of sides and each side includes at least two surface waveguides.
Phase control is introduced by coupling the first surface waveguide to a first phase controller operative for controlling the phase of a first light signal propagating in the first surface waveguide. The system architecture further includes excitation/collection optical networks and optional wavelength filtering to improve optical measurement precision by reducing illumination variation and supporting particle characterization.
Claims Coverage
The document contains three independent claims that cover an apparatus with a monolithically integrated substrate and two surface waveguides in parallel planes with phase control, an apparatus with through-thickness flow and coplanar pluralities of surface waveguides arranged in a polygonal pattern about the flow channel, and a method that interrogates fluid with an illumination pattern formed from a first surface waveguide and then couples a portion into a second surface waveguide after fluid interaction. Across these independent claims, the inventive features center on optofluidic integration of a flow channel with multiple surface waveguides in specified parallel/orthogonal plane relationships, polygonal placement of waveguides about the flow channel, and phase-controlled propagation using an optically coupled phase controller.
Monolithically integrated substrate with parallel-plane surface waveguides
An apparatus comprising a substrate defining a first plane with a flow channel located in a first region and conveying fluid along a first direction substantially orthogonal to the first plane, a first surface waveguide optically coupled with the flow channel located in a second plane substantially parallel with the first plane, and a second surface waveguide optically coupled with the flow channel located in a third plane substantially parallel to the second plane, wherein the substrate, the first surface waveguide, and the second surface waveguide are monolithically integrated and the second plane is between the first plane and the third plane.
Phase controller for controlling phase of a propagating light signal
The first surface waveguide is operatively coupled with a first phase controller that is operative for controlling the phase of a first light signal propagating in the first surface waveguide.
Through-thickness flow with polygonal arrangement of coplanar waveguides
An apparatus comprising a substrate having a thickness between a first major surface and a second major surface, a first flow channel operative for conveying fluid through the thickness, a first plurality of surface waveguides each optically coupled with the flow channel in a first region and being coplanar in a first plane within the first region, wherein the first plurality of surface waveguides is arranged in a polygonal arrangement about the flow channel in the first region, the polygonal arrangement having a plurality of sides, each side including at least two surface waveguides of the first plurality thereof.
Second coplanar plurality of optically coupled waveguides in a parallel plane
A second plurality of surface waveguides each optically coupled with the flow channel, the second plurality of surface waveguides being coplanar in a second plane within the first region, wherein the first major surface, the second major surface, the first plane, and the second plane are substantially parallel.
Interrogate with an illumination pattern and couple post-interaction light into a second waveguide
A method comprising conveying a first fluid through a flow channel arranged along a first direction through a first region of a substrate having a thickness between a first major surface and a second major surface, interrogating the first fluid with a first illumination pattern based on a first light signal emitted from a first surface waveguide of a first plurality of surface waveguides, and coupling a first portion of the first illumination pattern into a second surface waveguide of a second plurality of surface waveguides, wherein the first portion is coupled into the second surface waveguide after the first illumination pattern has interacted with the first fluid and wherein the first surface waveguide, the second surface waveguide, and the substrate are monolithically integrated such that the first major surface is between the second major surface and each of the first plane and the second plane.
Overall, claim coverage focuses on an optofluidic apparatus where a monolithically integrated substrate couples a flow channel with surface waveguides placed in parallel planes, including through-thickness flow with coplanar waveguide sets, and, in the apparatus of the first independent claim, includes phase control for propagating light. The method independent claim further specifies interrogating a fluid with an illumination pattern and coupling a portion of the post-interaction illumination into a second surface waveguide, consistent with the same monolithic and plane relationships.
Stated Advantages
Improved optical measurement precision by reducing illumination variation.
Supports particle characterization.
Documented Applications
Flow cytometry optofluidic system for interrogation of fluid/particles and supporting measurement and characterization using illumination patterns coupled through surface waveguides.
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