Bioanalysis Device Magnetic Particle Immobilization

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Solution Overview

Problem

Current methods for detecting cancer markers in early stages face challenges due to their low concentrations, requiring ultrasensitive detectors that can efficiently capture and quantify trace amounts of biomolecules without degrading the quality of quantification, especially when magnetic fine particles form aggregates under strong magnetic fields, leading to unfocused fluorescence spots and increased imaging time.

Innovation Solution

Confining a solution containing microscopic magnetic fine particles between flat substrates of high wettability in thin vertical thickness and applying a magnetic field from one substrate to evenly immobilize the particles, preventing aggregation and maintaining focus for precise quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If small magnetic fine particles are used to increase capture efficiency and particle density, then sensitivity and detection speed are improved, but magnetic susceptibility decreases making particle spreading difficult and causing bead-like aggregation under strong magnetic fields

Engineering Contradiction:
Improvedetection sensitivityVSAvoidparticle spreading difficulty
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent transitions from conventional horizontal particle placement to vertical confinement between substrates. By applying a magnetic field perpendicular to the substrate surface, particles are attracted and immobilized in a thin vertical gap, achieving high-density even distribution without horizontal aggregation. This dimensional change resolves the contradiction by using vertical magnetic attraction instead of horizontal spreading.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent changes the physical state and distribution parameters of magnetic particles by confining them in a thin liquid layer between substrates. The magnetic field strength and vertical confinement geometry are adjusted to achieve optimal particle density and distribution, transforming particles from aggregated beads into an even monolayer suitable for high-sensitivity detection.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If small magnetic fine particles are densely immobilized on a flat surface, then capture efficiency increases, but particle aggregation under strong magnetic fields creates mass that exceeds objective lens focal depth, causing fluorescence spots to go out of focus

Engineering Contradiction:
Improvecapture efficiencyVSAvoidfluorescence quantification quality
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent uses vertical confinement between two substrates to control particle positioning. By adjusting the gap thickness and magnetic field strength, particles are immobilized at a controlled vertical distance from the substrate, ensuring they remain within the objective lens focal depth while achieving high capture efficiency through dense packing.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Measurement precision

If autofocus function is added to capture unfocused fluorescence bright spots, then quantification completeness improves, but analysis complexity and imaging time increase

Engineering Contradiction:
Improvequantification completenessVSAvoidanalysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by confining and evenly distributing particles in the focal plane before fluorescence imaging begins. This pre-positioning eliminates the need for autofocus during imaging, as all particles are already in focus. The even distribution and vertical confinement ensure particles remain within focal depth, simplifying the imaging process and reducing analysis time.

Inventive Principle:
Principle #10Preliminary action

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

This method allows for even immobilization of magnetic fine particles, preventing light trapping and maintaining focus, enabling sensitive and efficient detection of trace biomolecules by ensuring that fluorescence bright spots remain in focus, thus improving the quality and speed of biomolecule quantification.

Implementation Method 1

a magnetic field is applied from the side of one of the flat substrates to attract the magnetic fine particles

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

microscopic magnetic fine particles of sizes no greater than 1 micron as the capture molecules

Methodology Applied
Scientific EffectMagnetism: Magnetism

Implementation Method 3

For the detection of biomolecules with fluorescent dye labels, observation is possible without interfering with the excitation and emission of the fluorescent dye

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10802017B2Bioanalysis device and biomolecule analyzer
Publication Date: 2020.10.13 HITACHI HIGH TECH CORP
  • US10802017B2 patent drawing
  • US10802017B2 patent drawing
  • US10802017B2 patent drawing

AI summary

Paramagnetic fine particles of 1 micron or less used under a strong magnetic field were shown to form beads-like aggregates along the magnetic flux, and become irregularly shaped as such a mass of particles combines with a flat particle layer. This phenomenon becomes a factor that degrades the quality of quantification in bioanalysis. By confining a solution of microscopic magnetic fine particles between flat substrates of high wettability as thin a vertical thickness as possible and attracting the magnetic fine particles under a magnetic field applied from the side of one of the flat substrates, the magnetic fine particles can be evenly immobilized in the form of a film on the substrate surface in a dispersion state, and the quality of the biomolecule quantification can be improved.