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Publication Number
US-11719700-B2
Publication Date
2023-08-08
Expiration Date
Abstract
Two or more upconverting particles are attached to each unit of one or more units of a chemical component in a sample, to form, for each unit of the chemical component, a multi-particle complex including the unit of the chemical component and two or more corresponding upconverting particles. The sample is illuminated by input light having a first wavelength. Light is received at an imaging sensor, the received light including output light generated by at least a portion of the upconverting particles attached to the units of the chemical component, the output light having a second wavelength that is shorter than the first wavelength. One or more images of the sample are captured from the received light. Based on the captured one or more images, a presence or a level of the chemical component in the sample is determined.
Core Innovation
A method is described for determining a presence or a level of a chemical component in a sample using upconversion-based detection. Two or more upconverting particles are attached to each unit of one or more units of a chemical component, where the two or more upconverting particles are configured to attach specifically to a corresponding unit of the chemical component, thereby forming a multi-particle complex comprising the unit of the chemical component and two or more corresponding upconverting particles.
The sample is illuminated by input light having a first wavelength. Light is received at an imaging sensor including output light generated by at least a portion of the upconverting particles attached to the one or more units of the chemical component, and the output light has a second wavelength that is shorter than the first wavelength. One or more images of the sample are captured from the received light including the output light.
Multi-particle complexes are identified in the one or more images based on at least one of proximity of the two or more upconverting particles to one another in each multi-particle complex or brightness of the output light generated by the two or more upconverting particles. Based on identifying the one or more multi-particle complexes in the one or more images, a presence or a level of the chemical component in the sample is determined.
The framework also supports multi-particle complex discrimination using proximity and/or brightness, and includes optional use of temporal and optical constraints such as time-gating and multiplexed excitation/collection across different excitation/emission bands to distinguish particle types and complexes. Near-field contact placement of the sample with the imaging sensor and sensor spectral selectivity to avoid wavelength filters are described as enabling robust imaging and detection of chemical components, including serology via antigen/antibody binding.
Claims Coverage
The document includes one independent method claim directed to determining a presence or a level of a chemical component by forming multi-particle complexes with two or more upconverting particles and imaging shorter-wavelength upconverted output, where inventive features include specific attachment, wavelength conversion, and identification of multi-particle complexes by proximity and/or brightness. Dependent claim coverage adds temporal separation between illumination and receiving, complex identification in a single image, excitation-band constraints for particle types, ratio differences between complexes for different chemical components, and attachment units as antibodies.
Specific attachment of multiple upconverting particles to chemical component units forming multi-particle complexes
Attaching two or more upconverting particles to each unit of one or more units of a chemical component in a sample based on the two or more upconverting particles being configured to attach specifically to a corresponding unit of the chemical component, to form, for each unit of the one or more units of the chemical component, a multi-particle complex comprising the unit of the chemical component and two or more corresponding upconverting particles.
Upconversion imaging using shorter-wavelength output generated by attached particles
Illuminating the sample by input light having a first wavelength; receiving light at an imaging sensor, the received light including output light generated by at least a portion of the upconverting particles attached to the one or more units of the chemical component, the output light having a second wavelength that is shorter than the first wavelength; capturing one or more images of the sample from the received light including the output light generated by at least the portion of the upconverting particles.
Proximity-based or brightness-based identification of multi-particle complexes in images
Identifying one or more multi-particle complexes in the one or more images based on at least one of a proximity of the two or more upconverting particles to one another in each of the one or more multi-particle complexes, or a brightness of the output light generated by the two or more upconverting particles.
Determining presence or level from identified multi-particle complexes
Based on identifying the one or more multi-particle complexes in the one or more images, determining a presence or a level of the chemical component in the sample.
Time-gated illumination and receiving with a time difference threshold
Illuminating the sample by input light at a first time; receiving the light at an imaging sensor at a second time, wherein the time difference between the first time and the second time is at least about 1 μs.
Complex identification in a single image based on proximity or brightness
Identifying one or more multi-particle complexes in a single image based on at least one of proximity of the two or more upconverting particles to one another in each multi-particle complex, or brightness of the output light generated by the two or more upconverting particles.
Excitation-band constrained particle-type selectivity for output wavelength generation
Each multi-particle complex comprises a first type of upconverting particles and a second type of upconverting particles, with a first wavelength of the input light being within a first excitation wavelength band and being outside a second excitation wavelength band, wherein the output light having the second wavelength is generated by the first type of upconverting particles.
Particle-type ratio differences between complexes corresponding to different chemical components
A method includes a sample having a first chemical component and additional units of a second chemical component, wherein multi-particle complexes include first and second types of upconverting particles, and wherein a ratio of a number of the first type of upconverting particles to a number of the second type of upconverting particles differs between the multi-particle complexes for the first chemical component and the multi-particle complexes for the second chemical component.
Attachment units as antibodies
Where the two or more attachment units comprise antibodies.
Overall claim coverage centers on forming multi-particle complexes by specific attachment of two or more upconverting particles to chemical component units, illuminating with input light to generate shorter-wavelength upconverted output at an imaging sensor, and identifying the complexes in images using proximity and/or brightness, then determining a presence or level of the chemical component from the identified complexes. Dependent claim refinements further constrain temporal separation between illumination and receiving, specify complex identification in a single image, add excitation-band relationships tied to particle types, introduce ratio-based distinctions across complexes for different chemical components, and specify antibody attachment units.
Stated Advantages
Enables determining a presence or a level of a chemical component in a sample using upconverted output light captured by an imaging sensor.
Supports identification of multi-particle complexes using proximity and/or brightness in the one or more images.
Allows complex discrimination using temporal and optical constraints, including time-gating and multiplexed excitation/collection across different excitation/emission bands to distinguish particle types and complexes.
Describes near-field placement with imaging sensor contact and sensor spectral selectivity to avoid wavelength filters.
Documented Applications
Serology using antigen/antibody binding to determine presence or level of chemical components, with described examples including antigen/antibody binding and pathogen-directed antibodies and recombinant viral proteins.
Chemical analysis in a sample, including determining presence/level such as concentration based on identified multi-particle complexes.
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