Enhanced cytometry for tissue characterization and screening
Inventors
Arvindan, Nallakkan • MEHI, Stephen • OU, Guanqing
Assignees
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Publication Number
US-12235264-B2
Publication Date
2025-02-25
Expiration Date
Abstract
An optical imaging system (100) includes a frame (102) designed to provide mechanical coupling between a first stage (104) and a second stage (106), a sample holding region (108) located on the first stage (104), a lens arrangement, and a sensor array. The lens arrangement is disposed between the first stage (104) and the second stage (106) and is designed to receive light from a sample at the sample holding region (108) on the first stage. The lens arrangement has a numerical aperture less than 0.1. The sensor array is coupled to the second stage (106) and is designed to receive light passing through the lens arrangement.
Core Innovation
An optical imaging system is provided for enhanced cytometry, tissue/cell characterization, and screening. The system includes a first stage with a sample holding region, and a frame configured to provide mechanical coupling between the first stage and a second stage. The first stage supports a substrate comprising a plurality of microfluidic channels such that, in operation, the sample holding region holding a sample is located below the substrate supported by the first stage.
A solution comprising fluorescently tagged probe molecules contacts the sample as the solution flows through the plurality of microfluidic channels. The system includes one or more lenses disposed between the first stage and the second stage, wherein the lenses receive light from the sample at the first stage. The arrangement of the one or more lenses has a numerical aperture less than 0.1, and the system can use a telecentric lens arrangement.
A sensor array is coupled to the second stage and configured to receive light passing through the one or more lenses to detect light fluorescing from the fluorescently tagged probe molecules. The disclosed system supports fluorescently tagged probe molecules delivered via a microfluidic substrate/channel to interrogate potentially whole tissue regions in a single field of view. The document also describes optional optical filters, an optional prism block to reduce excitation leakage and/or noise, substantially uniform flow rates through parallel channels, and high-throughput sequential or serial introduction of multiple probe solutions.
Claims Coverage
The independent claim contains inventive features that combine a microfluidic sample-contacting substrate, low numerical aperture lens optics, and a sensor array fluorescence detection arrangement. Additional claim refinements further specify lens type, optional filtering elements, optional prism block, sensor type, flow constraints, and probe loading sequences.
Microfluidic channels contacting a sample with fluorescently tagged probes
A first stage configured to support a substrate comprising a plurality of microfluidic channels such that the sample holding region holding a sample is located below the substrate supported by the first stage and a solution comprising fluorescently tagged probe molecules contacts the sample as the solution flows through the plurality of microfluidic channels.
Numerical aperture less than 0.1 lens arrangement between stages
One or more lenses disposed between the first stage and the second stage, configured to receive light from the sample at the first stage, wherein an arrangement of the one or more lenses has a numerical aperture less than 0.1.
Sensor array detecting fluorescing light from fluorescently tagged probe molecules
A sensor array coupled to the second stage and configured to receive light passing through the one or more lenses to detect light fluorescing from the fluorescently tagged probe molecules.
Telecentric lens arrangement
The one or more lenses include a telecentric lens.
Optical filter elements under the sample holding region
The first stage includes one or more of a bandpass filter, a longpass filter, and/or a polarization filter positioned under the first stage sample holding region.
CMOS sensor array for detection
Detecting light fluorescing from the fluorescently tagged probe molecules using a CMOS sensor array.
Substantially constant flow rate through microfluidic channels
Flowing a solution at a substantially constant flow rate through a plurality of microfluidic channels.
Prism block disposed over a substrate
Disposing a prism block over a substrate.
Overall, the claim set centers on an optical imaging system where fluorescently tagged probe molecules contact a sample via microfluidic channels, fluorescence is collected through a low numerical aperture lens arrangement, and a sensor array detects the resulting fluorescing light. Dependent claims narrow this with telecentric lens optics, optional filter elements, a prism block, substantially constant flow through parallel channels, and detection using a CMOS sensor array.
Stated Advantages
Enables enhanced cytometry for tissue/cell characterization and screening using fluorescence detection from fluorescently tagged probe molecules.
Supports detection across potentially whole tissue regions in a single field of view.
Supports high-throughput sequential or serial introduction of multiple probe solutions.
Can reduce excitation leakage and/or noise using an optional prism block and/or optical filters.
Documented Applications
Tissue/cell characterization and screening using an enhanced cytometry optical imaging system with fluorescently tagged probe molecules delivered through microfluidic channels.
Determining binding and target concentration across potentially whole tissue regions using fluorescence signal characteristics in a single field of view.
High-throughput detection with sequential/serial introduction of multiple probe solutions for screening.
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