Nucleic Acid Analyzer Substrate With Microstructure Bead Alignment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current nucleic acid analysis methods require several days to analyze all human genes, have low throughput due to random arrangement of DNA fragments, and necessitate expensive detection apparatuses with high numerical aperture lenses, leading to longer data transmission times and increased costs.

Innovation Solution

A reaction device with a substrate featuring regularly arranged microstructures for immobilizing microparticles, allowing for high-density arrangement and detection using a two-dimensional sensor with fewer pixels, reducing data transmission time and eliminating the need for high numerical aperture lenses, while preventing microparticle peeling during solution application.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If microparticles are immobilized randomly on the substrate, then the density of particles on the plate can be increased, but the number of pixels required in the two-dimensional sensor increases and data transmission time becomes longer

Engineering Contradiction:
Improvedensity of microparticles on substrateVSAvoiddata transmission time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The substrate is divided into multiple regions with different microparticle densities. High-density regions are placed where sensor pixels can efficiently detect fluorescence, while low-density regions reduce the total number of detectable particles. This segmentation allows the system to analyze fewer particles at ultra-high density locations, reducing data transmission time while maintaining overall high throughput.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different areas of the substrate have different microparticle densities optimized for their specific detection purposes. Regions closer to the sensor have higher density for maximum particle capture, while other regions have lower density to reduce redundant data. This local optimization of particle density allows the system to achieve high throughput without requiring all pixels to process data from equally dense regions.

Inventive Principle:
Principle #3Local quality

2Productivity

If microparticles are arranged in high density, then the number of DNA fragments that can be analyzed increases, but expensive condensing lenses with large numerical aperture are required

Engineering Contradiction:
Improvethroughput of analysisVSAvoiddetection apparatus cost
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The substrate is divided into multiple regions with different microparticle densities. Ultra-high density regions are strategically placed where the optical system can efficiently collect fluorescence without requiring large numerical aperture lenses. Lower density regions are distributed elsewhere, allowing the system to achieve high overall throughput while using simpler, less expensive optical components.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microparticle density is locally optimized across different substrate regions. Instead of uniformly high density throughout, the system concentrates particles in specific high-density zones that can be effectively detected by the available optical system, while other regions have reduced density. This allows high productivity without requiring expensive high-NA condensing lenses for the entire substrate area.

Inventive Principle:
Principle #3Local quality

3Ease of operation

If reaction solutions are sent to perform ligation reactions on randomly arranged beads, then the enzymatic reactions can proceed, but the beads are peeled off from the substrate by resistance at the time of sending solutions

Engineering Contradiction:
Improveligation reaction performanceVSAvoidmicroparticle immobilization stability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The substrate is segmented into regions with optimized microparticle densities that account for fluid flow dynamics. Regions with higher particle density are positioned where solution flow resistance is minimized, reducing the force that would cause bead peeling. This spatial segmentation allows ligation reactions to proceed effectively while maintaining bead stability during solution application.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microparticle density and distribution are locally optimized to match the fluid flow characteristics of the reaction system. Areas experiencing higher shear stress from solution flow have adjusted particle densities and positioning that reduce peeling forces, while still maintaining sufficient particle concentration for effective ligation reactions. This local optimization balances reaction performance with immobilization stability.

Inventive Principle:
Principle #3Local quality

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

Enables high-throughput nucleic acid sequence analysis with reduced data detection time and lower equipment costs, utilizing magnetic microparticles immobilized via microstructures for efficient fluorescence isolation and detection.

Implementation Method 1

utilizing magnetic microparticles immobilized via microstructures

Methodology Applied
Scientific EffectMagnetic force: Magnetism

Implementation Method 2

efficient fluorescence isolation and detection

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9207235B2Nucleic acid analyzer, reaction device for nucleic acid analysis and substrate of reaction device for nucleic acid analysis
Publication Date: 2015.12.08 HITACHI HIGH TECH CORP
  • US9207235B2 patent drawing
  • US9207235B2 patent drawing
  • US9207235B2 patent drawing

AI summary

Provided is a reaction device for nucleic acid analysis wherein microparticles, which carry a nucleic acid to be detected having been immobilized thereon, are aligned in a lattice form on a substrate according to the pixel size of a two-dimensional sensor. By this reaction device for nucleic acid analysis which is provided with a channel-forming reaction chamber on the substrate (101), the nucleic acid having been immobilized on the microparticles (103) on the substrate (101) is detected. The microparticles (103), which carry the nucleic acid to be detected having been immobilized thereon, are arranged by microstructures (102) aligned on the substrate (101).