Abstract: Methods and systems for time-domain and wavelength domain resolved multiplexed time-resolved fluorescence of a sample having at least one of a first fluorescent label bound to a first analyte and a second fluorescent label bound to a second analyte. The sample also includes a third fluorescent label bound to a third analyte and a fourth fluorescent label bound to a fourth analyte. The first and second fluorescent labels emit wavelengths having a first and second lifetime. The third fluorescent label comprises an upconverting phosphor (UCP) emitting at a wavelength having a third lifetime, and the fourth fluorescent label comprises an infrared dye emitting at wavelength having a fourth lifetime. The methods and systems measure as a function of time intensities of at least one of more of the first, second, third, and fourth fluorescent labels.

Abstract: A computer-implemented system and method for template-based imaging are disclosed. A first image of a first slide, a second image of a second slide, and a third image of a third slide are received, wherein the third image includes a representation of a sample disposed on the third slide. Values of pixels of a template image that are associated with a plurality of features common to the first and second slides and represented in the first and second images are set to a non-background value and values of pixels of the template image not associated with the plurality of features are set to a background value. An offset between the template image and the third image is developed and coordinates of pixels in the third image that are associated with the representation of the sample are determined in accordance with the offset.

Abstract: Systems, including methods and apparatus, for growing viable monoclonal colonies, identifying them as monoclonal after their viability has been demonstrated, and picking and placing them into a target environment. The methods may include plating cells at low density in a well, capturing at a first time shortly after plating a series of vertically spaced-apart images of the well showing locations of the cells, capturing at a second, later time images of the same well showing locations of candidate cell colonies, determining a likelihood that the candidate colonies are monoclonal based on information in the first set of images, and, based on the likelihood, picking candidate colonies using a picking head for transfer to a target environment.

Abstract: A well tray includes a base including an upper surface, a lower surface and at least one edge surface connecting the upper surface to the lower surface. The at least one edge surface defines a slot. The slot is in communication with a magnet receiver at least partially defined between the upper surface and the lower surface. The magnet receiver is configured to slidably receive a removable magnet. The tray includes a plurality of wells disposed on an upper surface of the base.

Abstract: In one aspect, a method for inspecting features of an image using an image inspection controller that includes a processor communicatively coupled to a memory is described. The method includes receiving, at the processor, an input image, performing, on the input image, one of a semantic segmentation process and an object classification process to generate an output image, and prompting a user to select between approving the displayed output image, and at least one of i) performing an additional semantic segmentation process on the displayed output image, and ii) performing an additional object classification process on the displayed output image.

Abstract: Microscope imaging system and method for bolus formation and detection. In an exemplary method, immersion fluid may be delivered onto a front end of an objective of the imaging system to form one or more boluses. Each bolus may have a rounded outer surface intersected by an optical axis defined by the objective. At least a portion of each bolus may be illuminated. Light may be detected from each illuminated bolus to create detection data. A value representing a size of each bolus may be determined using the detection data. Delivery of the immersion fluid may be adjusted, if needed, based on the value(s) determined.

Abstract: System, including methods and apparatus, for identifying and picking spectrally distinct colonies. In an exemplary method, a filter may be received in an optical path extending from a light source to a grayscale image detector. The filter may be configured to increase an intensity difference between a first type of colony and a spectrally distinct second type of colony. Colonies including both types may be received in the optical path. An image of the colonies may be obtained with the grayscale image detector. At least one of the types of colony may be identified in the image. One or more colonies of the at least one type may be picked robotically.

Abstract: A system and method for analyzing images using programmable device is disclosed. A sequencer operating on the non-transitory programmable device applies the first image analysis step to the first image to develop annotated training data. Specifications of the first image and the first image analysis step are developed using a graphical user interface operating on a computer. In addition, a machine learning system trainer operating on the programmable device trains an untrained machine learning system to develop a trained machine learning system. When the trained machine learning system is presented with the first image as an input, the trained machine learning system develops a prediction of the annotated training data. In addition, the sequencer analyzes a second image by undertaking a workflow, wherein the workflow is received from the computer and is specified using the graphical user interface and comprises a second image analysis step that that specifies operating the trained machine learning system.

Abstract: The invention relates to a method for a computer device, for detecting an optimal candidate compound based on a plurality of samples comprising a cell line and one or more biomarkers, and a plate map configuration, wherein the plate map configuration is providing locations of samples comprising cell lines exposed to one or more biomarkers and different concentrations of a candidate compound forming at least one concentration gradient, the candidate compound being comprised in a plurality of candidate compounds, said method comprising generating (310) phenotypic profiles of each concentration gradient of each of the plurality of candidate compounds at a plurality of successive points in time to form a plurality of compound profiles, wherein generating phenotypic profiles comprises the steps obtaining (312) image data depicting each sample comprised in the concentration gradient, generating (314) a class-label and a class for each cell of the samples based on the image data, detecting (320) the optimal candidat

Abstract: A method and system for autofocusing an objective lens in a microscope system are disclosed. A decentered aperture is disposed in an optical path between an objective lens and an image plane of an image capturing device and a plurality of reference images are captured. Each reference image is captured when the objective lens is positioned at a corresponding z-position of a plurality of z-positions along an axis of travel of the objective lens and the optical path is at least partially occluded by the decentered aperture. At least one reference image of the plurality of the reference images is associated with a best focus position. The plurality of reference images are analyzed to develop a plurality of pattern locations, wherein each pattern location represents a position of a pattern formed on the image plane when a corresponding reference image was captured. The objective lens is positioned in accordance with the best focus position and the plurality of pattern locations.

Abstract: A computer implemented system and method for generating a focus corrected image of a sample disposed on a sample holder of an imaging system is disclosed. The imaging system includes an image sensor and a lens moveable relative to the image sensor between a first position and a second position. A characteristic map of the lens is developed that associates coordinates of each pixel of an image generated by the imaging sensor with one of a first plurality of locations of the lens between the first position and the second position. An image generator develops an output pixel of a focus-corrected image of a sample from a plurality of images of the sample acquired when the lens is positioned at a corresponding one of a second plurality of locations of the lens between the first position and the second position.

Abstract: An object such as a cell colony may be picked from a plurality of objects by acquiring an image of the objects and an image of a pipette tip. The image of the objects is analyzed to select an object of interest. The selected object is associated with a coordinate position. Based on the coordinate position, the pipette tip is positioned over the selected object. An image of the pipette tip is then acquired and analyzed. The pipette tip is associated with a coordinate position. A positional error between the coordinate position of the selected object and the coordinate position of the pipette tip is determined. Based on the positional error, the pipette tip and/or a sample holder supporting the objects is moved to align the pipette tip over the selected object, by matching the coordinate position of the pipette tip with the coordinate position of the selected object.

Abstract: A template-based image analysis system and method are disclosed. A slide is loaded in a high-content image system (HCIS), wherein the slide includes a plurality of reference marks and a plurality of sample locations. An acquired images data store has previously acquired images stored therein. An image acquisition module acquires an image of the slide from the high-content imaging system. A feature identification module develops a binary image of the acquired image, wherein the binary image identifies areas associated with reference marks. A template generation module generates a template in accordance with the previously acquired images and a template alignment module aligns the generate template with the binary image. An offset calculation module determines an offset between the template and the binary image and an image segmentation module determines the coordinates of pixels of the acquired image that are associated with the sample locations in accordance with the calculated offset.

Abstract: A computer-implemented system and method for analyzing a biological sample are disclosed. A sequence of images of the biological sample from an image capture device are received from an image capture device, wherein each image of the sequence of images is acquired at a particular focal plane of the biological sample. In addition, an object map is developed from the sequence of images and the object map is analyzed to measure a three-dimensional characteristic of a particular object. The object map comprises a plurality of object map planes, each object map plane is associated with one image of the sequence of images, and pixels of the object map planes associated with the particular object in the sequence of images are assigned a unique identifier associated with the particular object.

Abstract: A high content imaging system and a method of operating the high content imaging system are disclosed. A microscope has a first objective lens and a second objective lens, and an objective lens database has first and second transformation values associated with the first and the second objective lenses, respectively. A microscope controller operates the microscope with the first objective lens to develop first values of acquisition parameters. A configuration module automatically determines second values of the acquisition parameters using the first values of the acquisition parameters, first transformation values associated with the first objective lens, and second transformation values associated with the second objective lens. The microscope controller operates the microscope using the second objective lens and the second values of the acquisition parameters.

Abstract: System and method using a projected reference to guide adjustment of a correction optic. In an exemplary method, a reference may be projected onto an imaging detector by propagation of light generally along an optical axis that extends from the reference, through an objective, to a surface of a sample holder, and from the surface, back through the objective, to the imaging detector. The light may propagate through an off-axis aperture located upstream of the imaging detector and spaced from the optical axis. A plurality of images of the reference may be captured using the imaging detector, and with a correction optic at two or more different settings. A setting for the correction optic may be selected based on the plurality of images, and a sample may be imaged while the correction optic has the selected setting.

Abstract: In one aspect, a method for inspecting features of an image using an image inspection controller that includes a processor communicatively coupled to a memory is described. The method includes receiving, at the processor, an input image, performing, on the input image, one of a semantic segmentation process and an object classification process to generate an output image, and prompting a user to select between approving the displayed output image, and at least one of i) performing an additional semantic segmentation process on the displayed output image, and ii) performing an additional object classification process on the displayed output image.

Abstract: A plenum assembly configured for electrophysiology assays, such as patch clamp techniques, includes one or more ground electrode assemblies. The ground electrode assemblies are individually removable from a plenum base of the plenum assembly in a non-destructive manner, and may be reinstalled in the plenum base in a manner that reestablishes electrical contact with ground circuitry without requiring soldering or other additional steps. A rejuvenating apparatus is provided for rejuvenating one or more ground electrode assemblies removed from the plenum base.

Abstract: Systems and methods for autofocusing an objective lens in a microscope system. A self-calibrating autofocus system includes a light source, a decentered aperture, and image-capturing device. The system may be connected to the microscope system so that the light source generates a light on an optical path that includes the objective lens and a plate having a reference surface proximal to a sample holding component. The image capturing device images a reflection of light from the reference surface as the objective lens moves to a series of z-positions. A reference calibration slope is generated for the objective lens by determining positions of the images taken at the z-positions of the objective lens. At least one image having a particular attribute corresponds to a best focus position. The objective lens is moved to predicted best focus or preferred offset from calibrated best focus using the reference calibration slope.

Abstract: A plenum assembly configured for electrophysiology assays, such as patch clamp techniques, includes one or more ground electrode assemblies. The ground electrode assemblies are individually removable from a plenum base of the plenum assembly in a non-destructive manner, and may be reinstalled in the plenum base in a manner that reestablishes electrical contact with ground circuitry without requiring soldering or other additional steps. A rejuvenating apparatus is provided for rejuvenating one or more ground electrode assemblies removed from the plenum base.