Dosimeters including lensless imaging systems

Inventors

Fine, Alan Marc

Assignees

Alentic Microscience Inc

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Publication Number

US-11061031-B2

Patent

Publication Date

2021-07-13

Expiration Date


Abstract

Among other things, a method comprises imaging a sample displaced between a sensor surface and a surface of a microscopy sample chamber to produce an image of at least a part of the sample. The image is produced using lensless optical microscopy, and the sample contains at least blood from a subject. The method also comprises automatically differentiating cells of different types in the image, generating a count of one or more cell types based on the automatic differentiation, and deriving a radiation dose the subject has absorbed based on the count.

Core Innovation

The invention provides dosimeters for radiation biodosimetry that use lensless optical microscopy to image a blood sample in a microscopy sample chamber with the sample positioned between a sensor surface and a chamber surface. Cells in the imaged blood sample are automatically differentiated and classified in the generated image, producing cell-type counts from the image.

The method detects labeled antibodies in the lensless optical microscopy image, where the labeled antibodies are bound to cells of one or more different types based on the labeled antibodies being directed against cells of the one or more different types. Based on the detected labeled antibodies and the classification of cells in the image, counts of the cells of the one or more different types are generated, including counts relevant to lymphocytes.

Based on the generated cell-type counts, a radiation dose of the subject is derived. The approach supports optional corrections associated with the counts, including volume correction, dilution correction, and spacing corrections, and it can further support longitudinal estimation through a lymphocyte depletion model based on time-separated samples.

Claims Coverage

The independent claim set is represented by one independent method claim, with additional dependent claims that refine the targeting of cell types/antigens, imaging and processing constraints, and longitudinal lymphocyte depletion modeling. The independent claim comprises five main inventive functional blocks: antibody labeling, lensless optical microscopy imaging, detecting antibody-bound cells, generating cell-type counts, and deriving a radiation dose based on those counts.

Labeled antibodies bound to different cell types

adding labeled antibodies to a blood sample of a subject, producing an image of the blood sample using lensless optical microscopy, the blood sample including the labeled antibodies; detecting the labeled antibodies in the image, wherein the labeled antibodies are bound to cells of one or more different types in the image based on the labeled antibodies being directed against the cells of the one or more different types

Lensless optical microscopy image of the labeled blood sample

producing an image of the blood sample using lensless optical microscopy, the blood sample including the labeled antibodies

Cell-type counts generated from detected antibody binding

generating counts of the cells of the one or more different types in the image based on the labeled antibodies in the image

Radiation dose derived from cell-type counts

based on the counts, deriving a radiation dose of the subject

Across the independent method and its dependents, the claim coverage centers on lensless optical microscopy of antibody-labeled blood, detection of labeled antibodies bound to cells of different types, generation of cell-type counts from the image, and derivation of radiation dose from those counts. Dependent claim refinements further specify targeted cell antigens, imaging resolution constraints, and longitudinal lymphocyte depletion estimation based on samples at different times.

Stated Advantages

Enables deriving a radiation dose of the subject based on cell-type counts generated from a lensless optical microscopy image of a labeled blood sample.

Supports automated differentiating and classifying of cells in the imaged blood sample to generate cell-type counts.

Supports longitudinal estimation of lymphocyte depletion using first and second blood samples taken at first and second different times.

Allows optional volume, dilution, and spacing-related corrections associated with the generated counts.

Documented Applications

Radiation biodosimetry using a dosimeter that images a blood sample by lensless optical microscopy to derive radiation dose from cell-type counts, including lymphocyte-related analysis.

Longitudinal lymphocyte depletion estimation for a subject using time-separated blood samples to support dose-relevant estimation.

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