Abstract: A system and method for analyzing images using a non-transitory programmable device is disclosed. A user interface generator operating on the non-transitory programmable device receives specifications of a first image of a biological sample and a first image analysis step. A sequencer operating on the non-transitory programmable device applies the first image analysis step to the first image to develop annotated training data, and a machine learning system trainer operating on the non-transitory 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.

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: An optical component for a microscope may include a low-autofluorescence substrate, or a substrate and a high-performance anti-reflective layer coating the substrate. An optical component may include a low-autofluorescence substrate and high-performance anti-reflective layer coating the low-autofluorescence substrate. The high-performance anti-reflective layer may be a low-autofluorescence high-performance anti-reflective layer. A microscope may include one or more such optical components.

Abstract: A system and a method to analyze a phenotypical response of cells to a treatment are disclosed in which a model development module receives images of a plurality of reference cell carriers and treatment information associated with the plurality of reference cell carriers, identifies parameters of cells in the image that distinguish those reference cell carriers to which the treatment has been applied from other reference cell carriers, and trains a model using the identified parameters. A high-content imaging system includes an image capture device, and the image acquisition module receives from the image capture device a plurality of images of cell carriers to be evaluated. The model application module applies the trained model to the plurality of images of the cell carriers to be evaluated to predict a concentration of the treatment applied to each of the cell carriers evaluated.

Abstract: Method and system for trans-illumination imaging. In an exemplary method, a sample is irradiated in a well. The sample may include biological cells and a liquid or semi-solid medium that forms a meniscus. The step of irradiating may be performed with an array of light sources generating light of respective light beams that are incident on the meniscus at different orientations from one another. One or more images may be detected. A proportional contribution of light from two or more subsets of the light sources to the one or more images may be controlled by differential energization of the two or more subsets relative to one another to compensate for refraction by the meniscus and improve contrast.

Abstract: A liquid immersion microscope objective assembly includes an objective, a liquid delivery system for delivering an immersion liquid to a lens of the objective, and a liquid return system for removing liquid from an area around the lens. The objective may be positioned below a sample container. Liquid is delivered to the lens so as to form a bolus between the lens and the sample container. Excess liquid drains into the return system, which may be done via a notch or a V-shaped channel. Additionally, the direction of flow through the delivery system may be reversed, such that liquid may also be removed from the area around the lens via the delivery system. The assembly may also be utilized to remove liquid from the underside of the sample container. The assembly may also include a leak sensor and/or an electrowetting device.

Abstract: Imaging systems and methods with scattering to reduce source auto-fluorescence and improve uniformity. In some embodiments, the system may include a plurality of trans-illumination light sources configured to irradiate an examination region with different colors of trans-illumination light, while a same diffuser is present in each optical path from the trans-illumination light sources to the examination region. The system also may comprise an excitation light source configured to irradiate the examination region with excitation light. The system may be configured to irradiate the examination region with each of the trans-illumination light sources and, optionally, with the excitation light source, without moving parts in any of the optical paths from the trans-illumination light sources. The system further may comprise an image detector configured to detect grayscale images of the examination region, and a processor configured to create a color trans-illumination image from grayscale images.

Abstract: A system and method of analyzing a biological sample using an imaging system are disclosed. An image acquisition module instructs the imaging system to obtain a label free image of a training biological sample and in response receives a first training image. The image acquisition module also instructs the imaging system to cause the training biological sample to fluoresce and obtain an image of the training biological sample undergoing fluorescence, and in response receives a second training image. An analysis module analyzing the second training image to generate a plurality of training cell characteristics, wherein each of the plurality training cell characteristics is associated with one of a plurality of training cells that comprise the training biological sample.

Abstract: In a method for measuring luminescence of a biological sample utilizing two different luminescence reagents, the sample is agitated to improve mixing with the second luminescence reagent, allowing for a shorter delay time between injection of the second reagent and measurement of the resulting luminescence activity. The improved mixing may also allow for a shorter measurement time, thereby improving throughput when assaying a large number of samples.

Abstract: A system and a method to analyze a phenotypical response of cells to a treatment are disclosed in which a model development module receives images of a plurality of reference cell carriers and treatment information associated with the plurality of reference cell carriers, identifies parameters of cells in the image that distinguish those reference cell carriers to which the treatment has been applied from other reference cell carriers, and trains a model using the identified parameters. A high-content imaging system includes an image capture device, and the image acquisition module receives from the image capture device a plurality of images of cell carriers to be evaluated. The model application module applies the trained model to the plurality of images of the cell carriers to be evaluated to predict a concentration of the treatment applied to each of the cell carriers evaluated.

Abstract: A system and method for analyzing multi-dimensional images includes a high content imaging system that includes an image capture device. An image acquisition module receives a series of images of a biological sample captured by the image capture device, and the series of images includes a sequence of image planes. A human interface module receives from a user computer specifications of a first image analysis step and a second image analysis step. The first image analysis step specifies a first image processing operation that processes an image plane of a series of images in accordance with at least another image plane of the series of images and the second image analysis step specifies a second image processing operation that processes each image plane of a series of images independently of the other image planes of the series.

Abstract: A method of generating in-focus images of measurement locations of a sample holder in a microscopy imaging system is provided. A camera sensor and an array of focusing optics are positioned at a first focal distance from the sample holder. A first image of a measurement location is acquired using the camera sensor. A candidate output image associated with the camera sensor and the array of focusing optics is developed in accordance with the first image. The camera sensor with the array of focusing optics is positioned at a second distance from the sample holder and a second image of the measurement location is acquired using the camera sensor. A portion of the candidate output image is updated in accordance with a portion of the second image in accordance with a selection criterion. The updated candidate image is transmitted.

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: The present invention is directed to multiplexed fluorescence detection, including time-resolved fluorescence (TRF) detection. A combination of spectral and temporal differences in fluorescence emission and spectral differences in excitation is used to enhance the ability to separate signals in an assay from multiple fluorescent labels. Different classes of labels may be utilized, including upconversion phosphors as well as lanthanide chelates and transition metal chelates. The methods may be implemented in optical plate readers, including cartridge-based multi-mode readers.

Abstract: Disclosed is a method for preparing dispersion gradients and an SPR injection method for determining full kinetics and affinity analysis in the presence of a competitor molecule. The SPR injection provides a dispersion gradient of two or more samples to a SPR flow cell and detector.

Abstract: Imaging systems and methods using an ancillary image detector for sample location. An exemplary system may comprise a light source to irradiate a sample on an irradiation axis, a first image detector on an optical axis oblique to the irradiation axis, and a stage. The system also may comprise a second image detector disposed on an imaging axis, and a drive mechanism configured to move the stage and the imaging axis relative to one another. The system further may comprise a processor configured to (a) receive an image of the sample detected by the first image detector, (b) determine a physical location for a region of contrast produced by the sample within the image, and (c) send a signal to the drive mechanism based on the physical location, to dispose at least part of the sample in a field of view of the second image detector.

Abstract: A referencing method for an optical biosensor system using a single sensing region is provided. The method involves limiting the ligand immobilized in a single sensing region to only a portion thereof. In one embodiment, this is accomplished by selectively deactivating a portion of the sensing surface to prevent immobilization of ligand to that portion. As a result, a reference response can be recorded in the same sensing region as a molecular interaction response. Thus, the bulk refractive index can be accurately accounted for in measuring the kinetics of a molecular interaction.

Abstract: The present invention is directed to a novel method to multiplex long lifetime fluorescent dyes using time-resolved fluorescence (TRF) detection. A combination of spectral and temporal differences in fluorescence emission is used to enhance the ability to separate signals in an assay from multiple dyes. Multiplexed TRF detection apparatuses and systems configured for performing all or part of any of the methods disclosed herein are also provided, particularly apparatuses and systems incorporating cartridge-based multi-mode readers.

Abstract: System of, and method for, trans-illumination imaging with use of interference fringes to enhance contrast and/or find focus. In an exemplary method, a coherence of light may be reduced upstream of a sample by scattering and mixing at least a portion of the light. The sample may be irradiated with the light of reduced coherence. An image of the sample may be detected, with the image being created with at least a portion of the light of reduced coherence that has passed through a plane defined by the sample. Image detection may be performed with the sample sufficiently defocused to form interference fringes in the image. The step of reducing a coherence of light may attenuate the interference fringes.

Abstract: A method of generating in-focus images of measurement locations of a sample holder in a microscopy imaging system is provided. A camera sensor and an array of focusing optics are positioned at a first focal distance from the sample holder. A first image of a measurement location is acquired using the camera sensor. A candidate output image associated with the camera sensor and the array of focusing optics is developed in accordance with the first image. The camera sensor with the array of focusing optics is positioned at a second distance from the sample holder and a second image of the measurement location is acquired using the camera sensor. A portion of the candidate output image is updated in accordance with a portion of the second image in accordance with a selection criterion. The updated candidate image is transmitted.