Method and apparatus for analyzing particles in a fluid
AssigneeBrightwell Technologies
InventorsPeter Oma, Jarret A. Diggins, Antonio J. G. Matias
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Abstract
A method and apparatus for analyzing particles in a fluid, such as proteinaceous particles in a pharmaceutical formulation intended for parenteral delivery, are disclosed. The method comprises arranging a fluid to form a wide and shallow stream, acquiring a sequence of magnified still images of the stream, and processing said images, so as to highlight images of particles in the flowing fluid. The apparatus includes a light source, a flow cell, a lens with increased depth of view, a detector array, and a processor for acquiring and processing the images of particles in the fluid stream.
Claims27
A method for analyzing particles in a sample fluid, comprising:
- arranging a sample fluid to form a sample fluid stream traveling in a direction of flow having a depth measuring between 20 microns and 1000 microns, and a width measuring between 25 and 10,000 microns in a direction of width;
- acquiring a sequence of magnified still images of the sample fluid stream, wherein the images are taken in a direction substantially perpendicular to:
- the direction of flow, and the direction of width of said sample fluid stream;
- and
- detecting and counting images of particles in said images of the sample fluid stream;
- wherein said detecting includes
- adjusting levels of illumination of said sample fluid stream so as to minimize a noise level present on said still images of sample fluid stream;
- measuring an actual level of illumination used to obtain a particular image of said sample fluid stream, for subsequent processing of such an image;
- subtracting a background image from said images of the sample fluid stream, forming background-corrected images, wherein said background image is substantially free of images of particles;
- and
- setting a threshold for the background-corrected images, so as to highlight images of particles present in the background-corrected images of the sample fluid stream.
An apparatus for analyzing particles in a sample fluid, comprising:
- a cell including
- a fluid inlet port for receiving a stream of the sample fluid in a direction of flow,
- a fluid outlet port for outputting the sample fluid stream,
- at least two transparent walls parallel to each other separated by a depth of between 20 microns and 1000 microns, and
- at least two side walls separated by a width of between 25 and 10,000 microns in a direction of width;
- an illumination means for illuminating said cell with light;
- an imaging means, coupled to said cell, for acquiring a sequence of magnified still images of the sample fluid stream flowing in said cell, wherein the images are taken in a direction substantially perpendicular to the direction of flow, and the direction of width;
- a suitably programmed processor for controlling the illumination means and the imaging means, as well as for detecting and counting images of particles in said images of the sample fluid stream, by,
- adjusting levels of illumination of said stream so as to minimize a noise level present on said still images of fluid stream,
- measuring an actual level of illumination used to obtain a particular image of said fluid stream, for subsequent processing of such an image,
- subtracting a background image from each of said images of the sample fluid stream, wherein said background image is substantially free of images of particles, and
- setting a threshold to thereby background-corrected images, so as to highlight images of particles present in the background-corrected images of the sample fluid stream.
Dependencies are inferred from the claim text.