Sequencing Chip Tapered Channels and PDMS Substrate
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Solution Overview
Problem
Current second-generation sequencing chips face issues with non-uniform fluid flow field distribution and deformation under negative imbibition pressure, leading to incomplete reagent replacement and compromised chip quality, which are not suitable for single-molecule sequencing technology.
Innovation Solution
A single-molecule sequencing chip design featuring a substrate with tapered channels and a transparent base layer, including a spacing layer to prevent sample cross-contamination, and a hydrophilic surface for reduced nonspecific adsorption, facilitating fluid flow and biochemical reactions without backflow and deformation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a large chip channel width is used to achieve high-throughput sequencing, then sequencing throughput is improved, but fluid flow field distribution becomes non-uniform and cover glass deformation occurs
Solution Approach 1:
The chip divides the large channel into multiple smaller parallel channels (e.g., 10-24 channels). Each channel has dimensions optimized for uniform fluid flow (width 100-500 μm, depth 50-200 μm), while the collective array of channels provides high-throughput sequencing capability. This segmentation resolves the contradiction by achieving both uniform flow fields in individual channels and high productivity through parallel processing.
Solution Approach 2:
The invention transitions from a single large two-dimensional channel to a three-dimensional array of multiple smaller channels with controlled depth (50-200 μm). This dimensional change allows optimization of each channel's cross-sectional geometry for uniform flow while maintaining high throughput through vertical stacking and parallel arrangement of multiple channels.
2Ease of operation
If negative imbibition pressure is applied for sample injection, then sample loading is achieved, but cover glass deformation occurs affecting chip quality
Solution Approach 1:
The chip employs a flexible PDMS substrate with integrated channels that can withstand negative imbibition pressure without deformation. The PDMS material provides elastic compliance, allowing the structure to flex under pressure and return to its original configuration, preventing permanent deformation of the cover glass and maintaining chip quality while enabling sample injection.
Solution Approach 2:
The chip uses a composite structure combining PDMS substrate with glass or PDMS cover glass. This composite material system provides both the flexibility needed to withstand negative pressure cycling and the optical clarity required for sequencing. The PDMS-glass composite maintains structural integrity under negative imbibition pressure while allowing sample injection.
3Productivity
If non-uniform flow field distribution occurs, then incomplete reagent replacement happens, but this affects biochemical reaction efficiency
Solution Approach 1:
Each channel in the array is designed with specific local geometric qualities (width 100-500 μm, depth 50-200 μm, tapered ends) that optimize fluid flow characteristics. The local channel geometry creates uniform velocity profiles and eliminates dead zones, ensuring complete reagent replacement. This local optimization of channel dimensions throughout the array ensures uniform flow fields and high biochemical reaction efficiency.
Solution Approach 2:
The channels incorporate curved or tapered geometries at their ends rather than sharp corners. This curvature design promotes smooth fluid flow transitions, eliminates flow separation and eddies, and ensures complete reagent replacement throughout the channel volume. The curved channel ends create uniform flow fields that enhance biochemical reaction efficiency.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The chip ensures uniform fluid flow, reduces substrate deformation, and prevents cross-contamination, enhancing the accuracy and efficiency of single-molecule sequencing by eliminating the need for barcodes and simplifying sample preparation and analysis.
Implementation Method 1
The flow field distribution of the chip is good, and the deformation rate of the chip is low, and the fluid can be fully flushed or replaced
Implementation Method 2
the base layer comprises a transparent layer and a spacing layer arranged on the surface of the transparent layer, the spacing layer being in contact with the first surface of the substrate, and grooves being provided on the spacing layer corresponding to the positions where the channels are located
Data Source
AI summary
Disclosed is a chip. The chip comprises a substrate (1) and a base layer (2) in pressing arrangement with the substrate; the substrate comprises a first surface (1a) and a second surface (1b) in opposite arrangement, reaction tank arrays formed by a plurality of flowing channels (11) are arranged on the first surface of the substrate at intervals, two oppositely arranged side walls (111, 112) of each flowing channel (11) stretch along the length direction of the flowing channel (11) and intersect at two ends of the flowing channel to form two tapered tail ends (113) with included angles, and a fluid inlet hole (12) and a fluid outlet hole (13) which are communicated with the second surface of the substrate are respectively provided on the surfaces of the two tapered tail ends (113); and the base layer (2) comprises a transparent base (21) and a spacing layer (22) arranged on the surface of the transparent base, the spacing layer (22) is in contact with the firs surface (1a) of the substrate, and a corrosion groove is provided on the spacing layer (22) corresponding to a position where the flowing channel (11) is located. The flow field distribution of the chip is good, the deformation rate of a base in the chip is low, and the fluid in the chip can be fully flushed or replaced. Also disclosed is an application of the chip.