Flow cytometry system and method
Inventors
Schreuder, Frederik • Hoekman, Marcel • Dekker, Ronald • Hosseini, Seyed Naser
Assignees
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Publication Number
US-9453791-B2
Publication Date
2016-09-27
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 invention relates to an optofluidic flow cytometry system that uses a substrate defining a flow channel operative for conveying fluid through a region of the substrate. The flow channel conveys fluid along a first direction that is substantially orthogonal to a plane of the substrate, and optical interrogation is performed by coupling light with surface waveguides located in parallel planes within the same region. The surface waveguides are optically coupled with the flow channel so that a detection zone of the fluid is interrogated using light propagating in the surface waveguides.
The system includes an excitation network and a collection network implemented as first and second surface waveguides arranged in different planes substantially parallel to respective substrate planes. Illumination and illumination collection are driven by controlling the phase of light propagating in a surface waveguide, where a first phase controller is optically coupled with a surface waveguide to control the phase of a first light signal. By controlling the phase, the shape of a first illumination pattern in the flow channel is shaped to be substantially uniform, with a low coefficient of variation for improved cell characterization.
The phase controller includes a waveguide core and a piezoelectric layer operatively coupled between electrodes so that strain is induced when a voltage is applied, thereby changing the effective refractive index and phase of light in the waveguide. The optofluidic architecture is implemented with wavelength-filtered collection for detection, and waveguide placement can be circular or polygonal around the flow channel in the region. The overall system architecture comprises a light source, the optofluidic system with excitation and collection waveguides, detectors, and a processor/control signals to support cell interrogation based on illumination interaction with the fluid.
Claims Coverage
The document includes three independent claims. Across these claims, the coverage centers on a substrate with an orthogonal or thickness-through flow channel, optically coupled surface waveguides located in substantially parallel planes, phase control of light propagating in the surface waveguides to shape an illumination pattern, and coupling illumination portions into additional surface waveguides after fluid interaction.
Substrate with orthogonal flow channel and first-plane surface waveguides
a substrate that defines a first plane, the substrate comprising a flow channel that is operative for conveying fluid along a first direction that is substantially orthogonal to the first plane, the flow channel being located within a first region of the substrate; a first surface waveguide that is optically coupled with the flow channel, the first surface waveguide being located in a second plane within the first region, wherein the second plane is substantially parallel with the first plane; a first phase controller operative for controlling the phase of a first light signal propagating in the first surface waveguide; and a second surface waveguide optically coupled with the flow channel in the first region and located in a third plane substantially parallel with the second plane.
Substrate thickness flow channel with coplanar excitation and collection surface waveguides
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 optically coupled with the flow channel in a first region and coplanar in a first plane within the first region; a first phase controller optically coupled with a first surface waveguide of the first plurality and operative for controlling the phase of a first light signal; and a second plurality of surface waveguides optically coupled with the flow channel and 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.
Illumination interrogation with orthogonal-plane surface-waveguide emission and post-interaction coupling
conveying a first fluid along a first direction through a first region; interrogating the first fluid with a first illumination pattern based on a first light signal emitted from a first surface waveguide that lies in a first plane orthogonal to the first direction in the first region; controlling the shape of the first illumination pattern by controlling the phase of the first light signal; and coupling a first portion of the first illumination pattern into a second surface waveguide that lies in a second plane orthogonal to the first direction in the first region after the first illumination pattern has interacted with the first fluid.
Across the independent claims, the document covers an optofluidic flow cytometry apparatus and method that interrogates a fluid in a flow channel with illumination generated from optically coupled surface waveguides in parallel or orthogonal planes, and shapes the illumination pattern by controlling the phase of light propagating in the surface waveguides. Additional coverage specifies multi-waveguide pluralities arranged around the flow channel, wavelength-filtered coupling, and piezoelectric strain-based phase control.
Stated Advantages
Improved cell characterization with a substantially uniform illumination pattern having a low coefficient of variation.
Documented Applications
Cell interrogation in an optofluidic flow cytometry system using illumination interaction with the fluid to support cell characterization.
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