Abstract: The formulations, systems, and methods disclosed herein permit automated preparation of specimens (e.g., biological specimens) for examination. The disclosed formulations, systems, and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation phases for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining specimens.

Abstract: 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.

Abstract: Sample application systems can include an extraction mechanism to remove a sample from sample containers, a sample vessel disposed on a deployment mechanism, where the deployment mechanism is arranged to move the sample vessel to receive a sample, an extraction mechanism washing station to wash the extraction mechanism, a sample applicator to remove a portion of the sample in the sample vessel and apply it onto a sample carrier, where the deployment mechanism can move the sample vessel to a sample application position, a sample vessel washing station to wash the sample vessel, where the deployment mechanism can move the sample vessel to the sample vessel washing station, a sample applicator washing station to wash the sample applicator after the sample has been dispensed onto the sample carrier, and a fluid control system to control flow of a fluid provided to the extraction mechanism and the sample applicator.

Abstract: A method for determining a mean cell volume for a blood sample includes: illuminating the sample with incident light at a plurality of illumination wavelengths and obtaining a two-dimensional image of the sample at each of the plurality of illumination wavelengths; identifying a plurality of cells that appear in each of the images; for each one of the plurality of cells, determining an integrated optical density corresponding to each of the plurality of illumination wavelengths; for each one of the plurality of cells, determining a cell volume based on the integrated optical densities corresponding to each of the plurality of illumination wavelengths; and determining the mean cell volume for the blood sample from the cell volumes for each one of the plurality of cells.

Abstract: Systems and methods for displaying measured values of a complete blood count (“CBC”) parameter include displaying the measured values of the CBC parameter obtained from a plurality of samples from a first lot of a quality control composition, where the displaying includes displaying a marker corresponding to each measured value from the first lot on a plot that includes a two dimensional coordinate system, and where the two dimensional coordinate system includes a first dimension corresponding to a time at which measured values of the CBC parameter were obtained, and a second dimension corresponding to a numerical value of the CBC parameter.

Abstract: Sample transport systems are described that move a sample carrier from one station to a next station in a sample processing systems. The systems include: a translating member; two or more sample carrier retaining devices attached to the translating member, wherein each of the two or more sample carrier retaining devices can include a retainer portion to temporarily retain one or more sample carriers; and a movement mechanism to move the translating member and the attached sample carrier retaining devices between a first position and a second position; wherein the sample carrier retaining devices are controlled and moved simultaneously to retain a sample carrier when the translating member reaches the first position and to release a sample carrier when the translating member reaches the second position to successively advance sample carriers in the sample processing systems.

Abstract: Systems, methods and computer program products for mapping coordinates of various imaging stations are described. In some implementations, cells (e.g., red blood cells) in a biological specimen can be used for determining the mapping information between the imaging stations. The use of cells allows a target image (e.g., an image of a sub-region of cells in the biological specimen) taken by one imaging station to be pattern-matched to a reference image (e.g., an image showing a larger region of cells in the biological specimen that also includes the sub-region) taken by another imaging station. Once the target image is matched to the reference image, point by point correspondence (and therefore coordinates) between the target image and the reference image can be established for computing the coordinate transformation to map the imaging stations.

Abstract: Methods for dispensing a fluid sample on a substrate include obtaining an image of a sample applicator in proximity to the substrate, where the image includes a first image of the sample applicator and a second image of the sample applicator, determining a height of the sample applicator relative to a surface plane of the substrate based on a distance between common portions of the first and second images, and dispensing the fluid sample onto the substrate using the sample applicator, where the dispensing includes: translating the sample applicator, translating the substrate, or translating both the sample applicator and the substrate to effect a relative translation between the sample applicator and the substrate; and maintaining the sample applicator within 2 microns of a target height relative to the surface plane of the substrate during the translating.

Abstract: This document describes methods, systems and computer program products directed to imaging blood cells. The subject matter described in this document can be embodied in a method of classifying white blood cells (WBCs) in a biological sample on a substrate. The method includes acquiring, by an image acquisition device, a plurality of images of a first location on the substrate, and classifying, by a processor, objects in the plurality of images into WBC classification groups. The method also includes identifying, by a processor, objects from at least some classification groups, as unclassified objects, and displaying, on a user interface, the unclassified objects and at least some of the classified objects.

Abstract: The apparatus disclosed herein features a substrate arm and gripper, a platform having a top surface located opposite the substrate when the substrate arm is in a specimen processing position and featuring at least one fluid port located on a surface of the platform facing the substrate and at least one vacuum port located on the surface of the platform facing the substrate, and during operation, the apparatus is configured to (a) dispense a first quantity of fluid from the at least one fluid port to fill a separation between the substrate and the platform, (b) dispense an additional quantity of fluid from the at least one fluid port into the separation to displace a portion of the first quantity of fluid, and (c) remove the portion of the first quantity of fluid from the separation through the at least one vacuum port.

Abstract: Systems and methods analyzing body fluids such as blood and bone marrow are disclosed. The systems and methods may utilize an improved technique for applying a monolayer of cells to a slide to generate a substantially uniform distribution of cells on the slide. Additionally aspects of the invention also relate to systems and methods for utilizing multi color microscopy for improving the quality of images captured by a light receiving device.

Abstract: A method of identifying the elements of a blood sample including placing an aliquot of blood on a transparent substrate such as a coverslip. The blood is allowed to stand and the cells to settle to form a layer or matrix. Inverted microscopy is used to identify the elements in the sample. Various forms of illumination may be used alone or in multiple combinations. The method improves the accuracy due to homogenous distribution of formed elements in the wet drop or aliquot, simplifies the method, lowers the cost of the test and results in a shortened analytical cycle time.

Abstract: Systems and methods for positioning a sample applicator relative to a substrate include: (a) obtaining an image of the sample applicator in proximity to the substrate, where the image includes a direct image region corresponding to the sample applicator and a first reflected image region corresponding to an image of the sample applicator reflected from a surface of the substrate; (b) determining a position of an edge of the sample applicator in the direct image region; (c) determining a position of a reflected edge of the sample applicator in the first reflected image region; (d) determining a distance between the edge of the sample applicator and the reflected edge of the sample applicator; and (e) determining the position of the sample applicator relative to the substrate based on the distance between the edges.

Abstract: The systems and methods disclosed herein permit automated preparation of biological specimens for examination. The disclosed systems and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a biological specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation cycles for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining biological specimens.

Abstract: Systems, methods and computer program products for mapping coordinates of various imaging stations are described. In some implementations, cells (e.g., red blood cells) in a biological specimen can be used for determining the mapping information between the imaging stations. The use of cells allows a target image (e.g., an image of a sub-region of cells in the biological specimen) taken by one imaging station to be pattern-matched to a reference image (e.g., an image showing a larger region of cells in the biological specimen that also includes the sub-region) taken by another imaging station. Once the target image is matched to the reference image, point by point correspondence (and therefore coordinates) between the target image and the reference image can be established for computing the coordinate transformation to map the imaging stations.

Abstract: 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.

Abstract: Sample application systems can include an extraction mechanism to remove a sample from sample containers, a sample vessel disposed on a deployment mechanism, where the deployment mechanism is arranged to move the sample vessel to receive a sample, an extraction mechanism washing station to wash the extraction mechanism, a sample applicator to remove a portion of the sample in the sample vessel and apply it onto a sample carrier, where the deployment mechanism can move the sample vessel to a sample application position, a sample vessel washing station to wash the sample vessel, where the deployment mechanism can move the sample vessel to the sample vessel washing station, a sample applicator washing station to wash the sample applicator after the sample has been dispensed onto the sample carrier, and a fluid control system to control flow of a fluid provided to the extraction mechanism and the sample applicator.

Abstract: The disclosure relates to methods and systems for automatically focusing multiple images of one or more objects on a substrate. The methods include obtaining, by a processor, a representative focal distance for a first location on the substrate based on a set of focal distances at known locations on the substrate. The methods also include acquiring, by an image acquisition device, a set of at least two images of the first location. The images are each acquired using a different focal distance at an offset from the representative focal distance. The methods further include estimating, by a processor, an ideal focal distance corresponding to the first location based on comparing a quality of focus for each of the images, and storing the estimated ideal focal distance and the first location in the set of focal distances at known locations.

Abstract: Systems and methods analyzing body fluids such as blood and bone marrow are disclosed. The systems and methods may utilize an improved technique for applying a monolayer of cells to a slide to generate a substantially uniform distribution of cells on the slide. Additionally aspects of the invention also relate to systems and methods for utilizing multi color microscopy for improving the quality of images captured by a light receiving device.

Abstract: Methods and systems for identifying reticulocytes in a blood sample deposited on a substrate include: illuminating the sample with incident light at two different wavelengths, obtaining a two-dimensional image of the sample corresponding to a first one of the wavelengths, and obtaining a two-dimensional image of the sample corresponding to a second one of the wavelengths; analyzing the images to identify a set of representative red blood cells; determining an area of each of the red blood cells in the set; determining a color value of each of the red blood cells in the set; and, for each one of the red blood cells in the set, identifying the red blood cell as a reticulocyte if the area of the red blood cell exceeds an area cutoff value and the color value of the red blood cell is less than a color cutoff value.