System and method for processing biological samples
Inventors
Kusner, Michael T. • Williams, Jeffrey
Assignees
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Publication Number
US-10093963-B2
Publication Date
2018-10-09
Expiration Date
Abstract
A system and method for processing and detecting nucleic acids from a set of biological samples, comprising: a molecular diagnostic module configured to receive nucleic acids bound to magnetic beads, isolate nucleic acids, and analyze nucleic acids, comprising a cartridge receiving module, a heating/cooling subsystem and a magnet configured to facilitate isolation of nucleic acids, a valve actuation subsystem including an actuation substrate, and a set of pins interacting with the actuation substrate, and a spring plate configured to bias at least one pin in a configurations, the valve actuation subsystem configured to control fluid flow through a microfluidic cartridge for processing nucleic acids, and an optical subsystem for analysis of nucleic acids; and a fluid handling system configured to deliver samples and reagents to components of the system to facilitate molecular diagnostic protocols.
Core Innovation
The invention is a system for processing and detecting nucleic acids using a cartridge with a fluidic pathway and a cartridge platform configured to receive the cartridge. The cartridge platform includes an access region aligned with the fluidic pathway, and the system includes a liquid handling system that delivers samples, reagents, and gases to cartridge fluidic pathways. The system includes heating/cooling to provide thermal processing associated with the nucleic-acid processing and detection in cartridge detection chambers, and a magnet configured for isolating nucleic acids from magnetic beads within the cartridge.
A valve actuation subsystem controls occlusion and opening of microfluidic fluidic pathways in the cartridge. The valve actuation subsystem includes a pin having a displacement region, and a spring coupled to the displacement region that biases the pin along a displacement axis extending through the first end, second end, and access region. The actuation substrate is translatable along an actuation axis perpendicular to the displacement axis, where a groove and a protrusion define open and closed configurations.
In the closed configuration, the groove aligns with the displacement region and the pin extends through the access region, and in the open configuration, the protrusion aligns with the displacement region and the pin is displaced away from the access region. An optical subsystem excites and detects nucleic-acid signals in detection chambers of the cartridge, including light emitting elements, excitation filters, a dichroic mirror, emission filters, and photodetectors with lenses. The cartridge construction supports sample/reagent port pairs, a waste chamber, a magnet housing region, shared fluid porting, fluidic pathways, detection chambers, and elastomeric occlusion.
Claims Coverage
Independent claims are directed to cartridge-based nucleic-acid processing and detection with a spring-biased pin valve actuation subsystem and defined open/closed configurations, and to a cartridge-based biological sample processing system with a pin occluding a fluidic pathway region in a first pin position and not occluding in a second pin position. Across the independent claims, two inventive features are specified for valve actuation, occlusion behavior, and open/closed state definition.
Spring-biased pin valve actuation subsystem with open/closed configurations
A valve actuation subsystem comprising a pin actuatable along a displacement axis, a spring coupled to a displacement region of the pin that biases the pin along the displacement axis, and an actuation substrate translatable along an actuation axis perpendicular to the displacement axis, wherein the system is operable between a closed configuration with a groove aligned with the displacement region and a first end of the pin extends through the access region, and an open configuration with a protrusion aligned with the displacement region and the first end of the pin displaced away from the access region.
Pin occlusion of an occlusion region versus access region with energetically coupled pin-substrate interface
A pin actuatable along a displacement axis between a first pin position and a second pin position, wherein the first end of the pin occludes an occlusion region of a fluidic pathway in the first pin position and does not occlude the access region of the fluidic pathway in the second pin position, together with an actuation substrate actuatable between a first substrate position and a second substrate position, and a pin-substrate interface aligning and energetically coupling at least one of the first substrate feature and the second substrate feature with the second end of the pin, wherein the system is operable between a closed state with the actuation substrate in the first substrate position and the first substrate feature aligned with the second end of the pin at the pin-substrate interface and the pin in the first pin position, and an open state with the actuation substrate in the second substrate position and the second substrate feature aligned with the second end of the pin at the pin-substrate interface and the pin in the second pin position.
Overall claim coverage centers on cartridge-based processing and detection in which valve actuation is implemented by a spring-biased pin and an actuation substrate that define a closed/open configuration, and in which the pin selectively occludes a fluidic pathway occlusion region while not occluding an access region in a corresponding pin position, with open/closed states established via an aligned and energetically coupled pin-substrate interface.
Stated Advantages
Documented Applications
Not explicitly described in patent.
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