Diagnostic apparatus
Inventors
Bresolin, Stefano • Calderwood, David A. • Heineck, Tobias M. • Newcomb, David • Paul, Chris • Pollard, Jaspar N> • Rodriguez, Rodolfo R. • Young, Demetris
Assignees
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Publication Number
US-10620190-B2
Publication Date
2020-04-14
Expiration Date
Abstract
An automated microscope apparatus, comprises an outer housing having an external wall; optionally but preferably an internal wall in said housing, and configured to form a first compartment and a separate second compartment in said outer housing; a microscope assembly in said housing, preferably in said first compartment; and a microprocessor in said housing, preferably in said second compartment; and optionally but preferably a heat sink mounted on said housing external wall, preferably adjacent said second compartment, with said microprocessor thermally coupled to said heat sink and operatively associated with said microscope assembly.
Core Innovation
An automated microscope apparatus includes an outer housing having an external wall, a heat sink mounted on the housing external wall, a microscope assembly in the outer housing, and a microprocessor in the outer housing. The microprocessor is thermally coupled to the heat sink and operatively associated with the microscope assembly, and the microscope assembly supports imaging of a chambered sample cartridge.
The apparatus architecture includes a support frame, a subframe, and a plurality of vibration isolators connecting the support frame to the subframe. An XYZ stage is connected to the subframe, and an optical stage is connected to the subframe, with the sample cartridge secured to the stage so that imaging and autofocusing are performed on at least one chamber.
An automated method and system aid detecting a disorder in a subject by securing a sample cartridge to the stage of an automated microscope, the sample cartridge including at least one chamber containing a biological sample collected from the subject. The microscope is autofocused on the at least one chamber, selected cells in the sample including at least neutrophils are imaged, and a count of at least neutrophils is generated as an aid to detecting a disorder, with optional repeating of imaging for at least one additional chamber on the cartridge.
Claims Coverage
The independent claims are directed to an automated microscope apparatus with heat-sink thermal coupling and a microscope assembly, a specific structural microscope assembly with vibration isolation and a passively cooled microprocessor assembly, an automated method for detecting a disorder using chambered cartridge imaging and neutrophil counting, an automated system for detecting a disorder using XYZ-stage chamber imaging with autofocusing and optional repetition, and a method for detecting a disorder using the automated microscope apparatus of the heat-sink/microprocessor configuration. Across these independent claims, the main inventive features include thermal coupling for the microprocessor and chambered cartridge microscopy workflows with autofocusing and neutrophil counts, optionally extending to differential cell counting across additional leukocyte types and repeated imaging across chambers.
Thermally coupled microprocessor with heat sink on outer housing
An automated microscope apparatus comprising an outer housing having an external wall, a heat sink mounted on the housing external wall, a microscope assembly in the outer housing, and a microprocessor in the outer housing with the microprocessor thermally coupled to the heat sink and operatively associated with the microscope assembly.
Vibration-isolated microscope assembly with XYZ and optical stages plus passively cooled microprocessor assembly
An automated microscope apparatus comprising an outer housing; a microscope assembly in the housing including a support frame, a subframe, a plurality of vibration isolators connecting the support frame to the subframe, an XYZ stage connected to the subframe, and an optical stage connected to the subframe; and a passively cooled microprocessor assembly in the housing.
Autofocused chamber imaging with neutrophil counting as aid to disorder detection
An automated method to aid detecting a disorder in a subject comprising securing a sample cartridge to the stage of an automated microscope, said sample cartridge comprising at least one chamber containing a biological sample collected from a subject; autofocusing the microscope on said at least one chamber; imaging selected cells in the sample including at least neutrophils; generating a count of at least neutrophils in the sample as an aid to detecting a disorder in the subject; and optionally repeating at least the imaging step for at least one additional chamber on the cartridge.
XYZ-stage chamber imaging system with autofocusing and optional repeated imaging
An automated system for detecting a disorder in a subject comprising an XYZ stage configured to secure a sample cartridge including at least one chamber containing a biological sample collected from a subject; an imaging system operatively associated with the XYZ stage and configured to image selected cells including at least neutrophils; an autofocusing system operatively associated with the imaging system and the XYZ stage and configured to focus the imaging system on the at least one chamber; means for generating a count of at least neutrophils in the sample as an aid to detecting a disorder in the subject; and a controller configured to optionally repeat at least the imaging for at least one additional chamber on the cartridge.
Automated microscope apparatus-based disorder detection method with neutrophil counts
A method for detecting a disorder in a subject with an automated microscope apparatus comprising providing an automated microscope apparatus having an outer housing with an external wall, a heat sink mounted on the housing external wall, a microscope assembly in the outer housing including a stage, and a microprocessor in the outer housing thermally coupled to the heat sink and operatively associated with the microscope assembly; securing a sample cartridge to the stage with at least one chamber containing a biological sample collected from a subject; autofocusing the microscope on the at least one chamber; imaging selected cells including at least neutrophils; generating a count of at least neutrophils as an aid to detecting a disorder; and optionally repeating at least the imaging step for at least one additional chamber on the cartridge.
Across the independent claims, the key claim coverage centers on an automated microscope apparatus with a microprocessor thermally coupled to a heat sink and a microscope assembly with vibration isolation and stage architecture, combined with an automated chambered-cartridge microscopy workflow in which autofocusing and imaging of selected cells including neutrophils generate neutrophil counts as an aid to detecting a disorder, with optional repetition for additional chambers. Some dependent claim coverage specifies differential leukocyte analysis and additional leukocyte-type counts, and constrains the disorder and sample context to infection/inflammation and to dairy-animal mastitis with milk, secretions, or colostrum in a cartridge having a defined number of chambers and teat-specific sampling.
Stated Advantages
A count of at least neutrophils is generated as an aid to detecting a disorder in a subject.
Optional repeating of imaging for at least one additional chamber on the cartridge.
Differential leukocyte analysis provides additional counts beyond neutrophils (neutrophils, lymphocytes, and macrophages) as part of disorder detection.
Documented Applications
Detecting disorders in dairy animals, particularly bovine mastitis, using a biological sample selected from milk, secretions, or colostrum collected in a sample cartridge with chambers containing milk from different teats.
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