Automated robotic microscopy systems
Inventors
Finkbeiner, Steven M. • Ando, Dale Michael • Daub, Aaron C.
Assignees
Publication Number
US-11361527-B2
Publication Date
2022-06-14
Expiration Date
2033-12-13
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Abstract
The present disclosure provides automated robotic microscopy systems that facilitate high throughput and high content analysis of biological samples, such as living cells and/or tissues. In certain aspects, the systems are configured to reduce user intervention relative to existing technologies, and allow for precise return to and re-imaging of the same field (e.g., the same cell) that has been previously imaged. This capability enables experiments and testing of hypotheses that deal with causality over time with greater precision and throughput than conventional microscopy methods.
Core Innovation
The invention provides automated robotic microscopy systems designed to facilitate high throughput and high content analysis of biological and non-biological samples such as living cells and tissues. These systems reduce user intervention compared to existing technologies and enable precise return to and re-imaging of the same field or cell that has been previously imaged. This capability empowers experiments and hypothesis testing related to causality over time with greater precision and throughput than conventional microscopy methods.
These systems include components such as an imaging device with a sample holder, a transport device for moving samples, processors communicating with these devices, and memory storing instructions for image acquisition and sample alignment. The invention allows automated handling from bulk sample storage to imaging and processing, including alignment of samples via fiduciary marks to ensure consistent imaging positions. The imaging devices may include advanced microscopes with cameras, light sources, filter wheels, and automated focusing components. The system software allows for scheduling, image stitching, alignment, object identification, tracking, and data extraction enabling longitudinal studies at single-cell resolution.
Claims Coverage
The patent includes two independent claims focusing on systems comprising a sample holder, imaging device, and robotic arm with features enabling precise positioning, imaging, and sample handling.
Automated sample handling and imaging with fiduciary mark alignment
System comprising a sample holder defining a cutout portion, an internal beveled edge, and bottom lip portion; an imaging device; and a robotic arm configured for automatic retrieval and placement of a sample on the imaging device. The system automatically identifies a fiduciary mark on the sample, moves the sample so the fiduciary mark matches a reference image position, and acquires an image of the sample.
Sample transport including retrieval from imaging device and placement on alternative surfaces
The robotic arm is configured to retrieve the sample from the imaging device and place it on a second surface, facilitating automated sample transport within the system.
Bulk sample storage with environmental control and robotic transfer
The system includes a bulk sample storage subsystem capable of storing multiple samples with heating or cooling elements, and a robotic arm configured to transfer samples to and from storage and the imaging device.
Sample identification and tailored imaging
Sample identification subsystem comprising a barcode reader in electronic communication with a processor, enabling sample-specific tailoring of image acquisition steps.
Sample holder designed for precise positioning and compatibility
The sample holder is sized to receive a sample with a 127.5 mm×85 mm footprint, includes walls defining a cutout, internal beveled edges within specified angular ranges, and an actuator to bias the sample into a consistent corner.
Imaging system components
Imaging device includes an inverted microscope body imaging from below, cameras with exposure of 30 ms or less (such as EMCCD cameras), a Xenon light source, and image acquisition includes multi-wavelength image deconvolution.
Method for sample positioning and longitudinal imaging
System configured to move the sample to an approximate stage location, automatically identify a fiduciary mark, align the sample to the reference image, acquire temporal series of images, and track objects within the sample over time.
The claims cover automated microscopy systems combining sample holders with specific structural features, robotic arms for automated sample handling and precise fiduciary-based alignment, bulk storage with environmental control, sample identification for tailored imaging, and imaging devices equipped with advanced components that facilitate high throughput, longitudinal imaging and data processing.
Stated Advantages
Reduces user intervention relative to existing technologies.
Enables precise return to and re-imaging of the same field or cell multiple times.
Facilitates experiments and testing hypotheses related to causality over time with greater precision and throughput than conventional methods.
Allows high throughput and high content analysis of living cells, tissues, and various sample types.
Supports automated sample handling including storage, identification, placement, alignment, imaging, and processing.
Permits flexible, runtime-adjusted imaging parameters tailored to specific samples or wells within multi-well plates.
Documented Applications
High throughput and high content analysis of biological samples such as living cells (e.g., neurons) and tissues.
Longitudinal imaging and tracking of individual cells over extended time periods (e.g., 96 hours or more).
Drug and genetic screens using multi-well plates with different experimental conditions per well.
Monitoring cellular health markers such as neurite morphology and mitochondrial degradation over time.
Automated transfection of primary neurons using liquid handling integrated into the system.
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