Plastic microfluidic separation and detection platforms
Inventors
Tan, Eugene • Kan, Cheuk Wai • Lam, Heung Chuan
Assignees
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Publication Number
US-11052398-B2
Publication Date
2021-07-06
Expiration Date
Abstract
Plastic electrophoresis separation chips are provided comprising a plurality of microfluidic channels and a detection window, where the detection window comprises a thin plastic; and the detection window comprises a detection region of each microfluidic channel. Such chips can be bonded to a support provided an aperture is provided in the support to allow detection of samples in the electrophoresis chip at the thin plastic detection window. Further, methods for electrophoretically separating and detecting a plurality of samples on the plastic electrophoresis separation chip are described.
Core Innovation
The disclosed invention relates to a plastic electrophoresis microfluidic separation chip and a laser-induced fluorescence detection platform for focused nucleic-acid analysis. The problem addressed is the need for rapid, high-resolution, high-SNR multi-lane plastic biochips in view of issues such as autofluorescence, bonding, and electroosmotic and DNA-to-wall interaction problems. The document describes reducing plastic autofluorescence relative to glass and enabling simultaneous multi-lane separation and detection in a plastic format.
A plastic chip component is described that includes a separation chip with a substrate layer and a cover layer, wherein one layer includes a plurality of grooves and the other includes a series of through holes. The top surface of the substrate layer and the bottom surface of the cover layer are bonded to form a first microfluidic channel connecting a sample to a plurality of second microfluidic channels, each second channel having a detection region at the termini of a separation region.
The document further specifies optical and material characteristics for the thin plastic layers, including selection of thin plastics from polyethylene, poly(carbonate), cyclic olefin polymers (COP), cyclic olefin copolymers (COC), norbornene thermopolymers, or a poly(acrylate) which essentially does not fluoresce light between 500 and 800 nm when excited between about 450 and 500 nm. A plastic support includes an anode portion with anode wells, a cathode portion with cathode wells, and a center portion with a detection window fabricated from a cut-out that overlaps each detection region.
Claims Coverage
The provided claims include one independent claim. The inventive aspects center on a bonded two-layer plastic separation chip forming one sample channel to multiple non-intersecting second channels with termini detection regions, overlapped detection regions by a thin cut-out detection window in a plastic support with anode/cathode well portions, and optical/material and thickness limits on the thin plastic layers and total plastic at the detection region.
Bonded two-layer plastic separation chip with first-to-multiple second microfluidic channels
A plastic chip component with a separation chip where one of the substrate layer and cover layer includes a plurality of grooves and the other includes a series of through holes, and where bonded top and bottom surfaces form a first microfluidic channel connecting sample to a plurality of second microfluidic channels, each second channel having a detection region at the termini of a separation region.
Thin plastic layer optical selection and thickness limits
The separation chip where each of the substrate layer and cover layer comprises one of the listed thin plastics, including a poly(acrylate) essentially not fluorescing light between 500 and 800 nm when excited between about 450 and 500 nm, and where each thin plastic layer has a thickness of less than 200 μm.
Plastic support with anode/cathode wells and detection window overlapping termini detection regions
A plastic support fixedly attached to the chip, having an anode portion with at least one anode well, a cathode portion with at least one cathode well and a center portion therebetween, where the center portion has a detection window fabricated from a cut-out in the plastic support that overlaps with the detection region of each of the plurality of second microfluidic channels such that the total thickness of plastic at the detection region is less than 400 μm.
Across the independent claim, the coverage emphasizes a bonded multi-channel plastic electrophoresis separation structure with termini detection regions, combined with a thin overlapped detection window in a plastic support that includes anode and cathode well portions, while using specified low-fluorescence plastic materials and thickness constraints at the detection region.
Stated Advantages
Enables low plastic autofluorescence compared to glass for laser-induced fluorescence detection.
Achieves high resolution for STR allelic ladder detection and single-base resolution with acceptable signal-to-noise as described in the document.
Supports detection of very low template copies/copy amount as described in the document.
Documented Applications
Clinical diagnostics.
Forensics.
Field or ruggedized use.
Drug resistance monitoring (as part of the described applications/domain examples).
STR sizing (including allelic ladder STR sizing as described in the document).
Sequencing (including sequencing profiles as described in the document).
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