Patterned Chip Depressions for Higher-Density Nucleic Acid Sequencing
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Solution Overview
Problem
The stability and accuracy of nucleic acid sequencing results on biochips are influenced by the shape and dimensions of geometric structures on the chip surface, affecting parameters such as clonal cluster stability, signal intensity, and sequencing alignment.
Innovation Solution
A patterned chip design with regularly arranged depressions, featuring interconnected geometric structures with specific dimensions and angles, enhances sequencing stability and accuracy by optimizing the arrangement density and facilitating simultaneous detection of multiple nucleic acid types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If geometric structures with larger dimensions are used on the chip surface, then detection sensitivity may be improved, but the arrangement density of detection sites decreases, reducing detection throughput
Solution Approach 1:
The patent transitions from two-dimensional planar detection sites to three-dimensional depression structures with varying depths (0-100 μm) and geometric configurations. This vertical dimensionality change allows detection sites to be stacked in layers, increasing arrangement density without sacrificing individual site detection sensitivity, thereby resolving the contradiction between sensitivity and throughput
Solution Approach 2:
The depression structures are nested within the chip substrate, with deeper depressions containing shallower ones or vice versa. This nesting arrangement allows multiple detection sites to occupy the same horizontal footprint at different vertical levels, maximizing spatial utilization and enabling high-density arrangement while maintaining adequate signal intensity for each site
2Productivity
If the chip surface is configured with patterned geometric structures, then arrangement density and surface utilization rate improve, but the complexity of chip manufacturing increases
Solution Approach 1:
The chip surface is segmented into multiple independent depression structures with standardized geometric parameters (depth 0-100 μm, horizontal dimensions 10 nm-100 μm). Each depression is a discrete, replicable unit that can be manufactured using automated patterning techniques, reducing overall manufacturing complexity while enabling high arrangement density through systematic repetition
Solution Approach 2:
The patent employs a limited set of standardized geometric parameters for all depression structures (depth ranges, horizontal dimensions, included angles of 10-170°). This parameter standardization allows for simplified manufacturing processes and quality control, as deviations can be monitored against fixed specifications rather than custom designs, thereby reducing manufacturing complexity while maintaining high arrangement density
3Measurement precision
If deeper geometric structures are used to enhance signal intensity, then sequencing accuracy improves, but the difficulty of precise manufacturing and quality control increases
Solution Approach 1:
The patent establishes specific parameter ranges for depression depth (0-100 μm) and horizontal dimensions (10 nm-100 μm) that balance signal intensity enhancement with manufacturability. These standardized parameters enable the use of conventional fabrication techniques with controlled precision, avoiding the need for ultra-precise manufacturing while still achieving sufficient signal intensity for accurate sequencing
Solution Approach 2:
Different regions of the chip can employ depression structures with optimized local parameters (varying depths, dimensions, and geometries) tailored to specific detection requirements. This local optimization allows critical detection sites to use deeper structures for enhanced signal intensity where needed, while less critical areas use shallower structures that are easier to manufacture, thereby balancing sequencing accuracy with manufacturing precision across the entire chip
Data Source
AI summary
The present application provides a chip, which includes a chip substrate, wherein the chip substrate is provided with regularly arranged depressions on at least one surface; the depression comprises, in sequence, a first geometric structure and a second geometric structure that are interconnected in a direction from a surface of the chip substrate toward a central part of the chip substrate. In the chip provided by the examples of the present application, the regularly arranged depressions are formed on the substrate, and the depression comprises, in sequence, the first geometric structure and the second geometric structure that are interconnected in the direction from the surface of the chip substrate toward the central part of the chip substrate, so that the morphological structure of the depressions in the present application facilitates substance exchange and diffusion between the liquid phase of a reaction reagent and active molecules on the surface of the chip during a biochemical reaction in a detection process (e.g., nucleic acid sequencing), thereby promoting the reaction to occur and thus obtaining better detection signals (including signal intensity and signal-to-noise ratio) and more accurate detection results.