Unitary biochip providing sample-in to results-out processing and methods of manufacture
Inventors
Selden, Richard F. • Tan, Eugene
Assignees
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Publication Number
US-9314795-B2
Publication Date
2016-04-19
Expiration Date
Abstract
A biochip for the integration of all steps in a complex process from the insertion of a sample to the generation of a result, performed without operator intervention includes microfluidic and macrofluidic features that are acted on by instrument subsystems in a series of scripted processing steps. Methods for fabricating these complex biochips of high feature density by injection molding are also provided.
Core Innovation
The claims describe a stationary, unitary plastic biochip comprising an injection-molded macrofluidic block, a fluidic plate, and a pneumatic plate. The macrofluidic block receives an unprocessed sample, contains foil-sealed liquid-reagent storage chambers, and transfers the processed sample to the fluidic plate. The fluidic and pneumatic plates include microfluidic features and through holes that connect their surfaces and align the plates for automated fluid handling.
The biochip architecture supports automated nucleic acid purification, amplification, electrophoretic separation, and optical detection under instrument control. Across the independent claims, specified variations include injection-molding fabrication, microfluidic features with draft angles of less than 2 degrees, and regions of at least one square centimeter wherein microfluidic features have a pitch of at least 1.00 mm. Embodiments split DNA into parallel reactions and use low-autofluorescence substrates.
Claims Coverage
The relevant claims comprise eight independent claims directed to a biochip and its component arrangements, covering eight inventive features.
Biochip with molded macrofluidic, fluidic, and pneumatic components
Claim 1 covers a biochip comprising an injection-molded macrofluidic block, fluidic plate, and pneumatic plate, wherein the macrofluidic block receives an unprocessed sample and transfers processed sample to the fluidic plate, the plates include microfluidic features and through holes for connection and alignment, and the block includes a foil-sealed liquid-reagent storage chamber.
Fluidic plate with low-draft-angle features
Claim 2 includes the component arrangement and reagent storage chamber of claim 1, with at least two microfluidic features on the fluidic plate having a draft angle of less than 2 degrees.
Biochip with at least one injection-molded component
Claim 3 covers a macrofluidic block, fluidic plate, and pneumatic plate with a foil-sealed liquid-reagent storage chamber, sample transfer, and through-hole alignment, wherein at least one of the three components is fabricated by injection molding.
Pneumatic plate with low-draft-angle features
Claim 4 includes the component arrangement and reagent storage chamber of claim 1, with at least two microfluidic features on the pneumatic plate having a draft angle of less than 2 degrees.
Fluidic plate with specified feature pitch
Claim 5 includes the component arrangement and reagent storage chamber of claim 1, wherein the fluidic plate has a region of at least one square centimeter in which at least two microfluidic features are at a pitch of at least 1.00 mm.
Pneumatic plate with specified feature pitch
Claim 6 includes the component arrangement and reagent storage chamber of claim 1, wherein the pneumatic plate has a region of at least one square centimeter in which at least two microfluidic features are at a pitch of at least 1.00 mm.
Macrofluidic block with specified feature pitch
Claim 7 includes the component arrangement and reagent storage chamber of claim 1, wherein the macrofluidic block has a region of at least one square centimeter in which at least two microfluidic features are at a pitch of at least 1.00 mm.
Injection-molded component with specified feature pitch
Claim 8 covers a macrofluidic block, fluidic plate, and pneumatic plate with a foil-sealed liquid-reagent storage chamber, sample transfer, and through-hole alignment, wherein at least one component is injection molded and contains a region of at least one square centimeter having at least two microfluidic features at a pitch of at least 1.0 mm.
The eight independent claims cover a biochip assembly comprising a sample-receiving macrofluidic block, a foil-sealed liquid-reagent storage chamber, and aligned fluidic and pneumatic plates, with claim-specific variations concerning injection-molding fabrication, microfluidic feature draft angles, and microfluidic feature pitch.
Stated Advantages
The system reduces operator intervention.
The system reduces fabrication costs.
Parallel neat and diluted DNA reactions avoid the need for quantitation.
The substrate and notch-filter configuration reduces plastic fluorescence background and improves the signal-to-noise ratio.
The system achieves single-base-pair resolution in STR profiling.
Documented Applications
Sample-in-to-results-out nucleic acid analyses, including DNA purification, PCR amplification, electrophoretic separation, and optical detection.
Short tandem repeat (STR) profiling using buccal-swab samples, generating electropherogram traces with labeled genetic-marker loci and peaks.
Bacterial pathogen detection.
Multiplex sequencing using blood samples.
Analytical applications displaying DNA fragment-size signal traces with markers from 100 to 600 bp.
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