Systems and methods for analyzing body fluids

摘要

Systems and methods analyzing body fluids contain cells including blood, bone marrow, urine, vaginal tissue, epithelial tissue, tumors, semen, and spittle are disclosed. The systems and methods utilize an improved technique for applying a monolayer of cells to a slide and generating a substantially uniform distribution of cells on the slide. Additionally aspects of the invention also relate to systems and method for utilizing multi-color microscopy for improving the quality of images captured by a light receiving device.

主权项

1. A system configured for analyzing red blood cells and white blood cells from a sample of a body fluid containing blood cells, the system comprising:
a. a feeder for storing new transparent substrates; b. an application station comprising a mixer, a body fluid reservoir, a diluent reservoir, and an applicator tip for dispensing the body fluid containing a homogenous and quantifiable number of blood cells onto a transparent substrate, wherein the mixer, the body fluid reservoir, and the diluent reservoir are fluidly connected, and wherein the applicator tip is fluidly connected to the mixer and is arranged above the substrate; c. a preparation station comprising a dispenser for dispensing fixative and stain onto the cells on the transparent substrate; d. an imaging station comprising:
i. a light source arranged on one side of the transparent substrate and configured to direct light through the transparent substrate to illuminate the blood cells on the transparent substrate; andii. a light receiving device arranged on a side of the transparent substrate opposite the light source and configured to capture at least one image of the blood cells corresponding to light in a first wavelength range of 400 to 470 nm transmitted through the cells without capturing a fluorescent emission or light reflected off the transparent substrate, and at least one image of the cells corresponding to light in a second wavelength range of 470 to 750 nm transmitted through the cells without capturing a fluorescent emission or light reflected off the transparent substrate; e. an advancer for moving the transparent substrate through the system in order from the feeder, to the application station, to the preparation station, and to the imaging station; f. a display comprising a graphical user interface (“GUI”) arranged to display images of cells: g. a computer comprising a microprocessor; and h. software instructions stored on a storage device for controlling the system, wherein when the microprocessor executes the software instructions the computer causes the system to:
i. fill the applicator tip with a volume of the body fluid;ii. position the applicator tip above the transparent substrate;iii. dispense a known volume of body fluid including a quantifiable number of blood cells out of the applicator tip and while ejection of the body fluid onto the transparent substrate is occurring, maintaining relative movement between the tip and the transparent substrate to lay down the entire known volume of body fluid in two or more rows over a defined area of the transparent substrate, wherein the applicator tip height above the transparent substrate, a flow rate of the body fluid out of the applicator tip, and a speed of the relative movement are controlled such that blood cells in the body fluid settle onto the transparent substrate in a layer that is about one cell thick and such that morphology of the blood cells is sufficiently preserved to enable image-based cell analysis;iv. fix and stain the cells on the transparent substrate;v. control the light source to illuminate the cells on the transparent substrate;vi. activate the light receiving device to capture at least one image of the red blood cells (“RBCs”) and at least one image of the white blood cells (“WBCs”) corresponding to light in the first wavelength range transmitted through the cells without capturing a fluorescent emission or light reflected off the transparent substrate, and at least one image of the red blood cells and at least one image of the white blood cells corresponding to light in the second wavelength range transmitted through the cells without capturing a fluorescent emission or light reflected off the transparent substrate;vii. store the images in a memory;viii. automatically analyze the images of the RBCs and WBCs to determine whether the body fluid sample dispensed onto the substrate is sufficiently dilute or concentrated to form the about one cell thick layer of blood cells for analysis, wherein if the analysis of the images indicates that the body fluid sample on the substrate is too concentrated, the system adds more diluent from the diluent reservoir to the mixer to further dilute the body fluid, and if the analysis of the images indicates that the body fluid sample on the substrate is too dilute, the system adds more body fluid or concentrated body fluid from the body fluid reservoir to the mixer to further increase the body fluid concentration on the substrate;ix. automatically analyze the images of the RBCs and WBCs to determine a RBC count per microliter of the sample of body fluid and a WBC differential for the sample including a count of each type of WBC per microliter of the sample of body fluid; andx. display color images of a plurality of the RBCs and of a plurality of the WBCs based on the images captured by the light receiving device, the results of the RBC count, and the results of the WBC differential and the WBC counts in the GUI of the display, wherein the GUI is configured to allow an operator to interact with the color images and sign off on the RBC count results and the WBC differential results.