Density-Driven Solvent Layering for Bead Sealing in Microarrays
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Solution Overview
Problem
Current methods for detecting low-concentration target molecules, such as disease markers, require extensive time and effort to prepare large numbers of small liquid droplet arrays for efficient bead sealing, making it difficult to apply to cases requiring millions of arrays.
Innovation Solution
A method involving the use of a first solvent with a substance and a second solvent of greater specific gravity, optionally containing surfactants like TWEEN 20 or Triton X-100, to efficiently seal beads, nucleic acid, protein, virus, cells, or lipid membrane complexes into an array by layer substitution, allowing for high-density storage and detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional centrifugal force methods are used to seal beads into arrays, then bead sealing can be achieved, but it requires extensive time and effort to prepare large numbers of arrays and uses strong centrifugal force
Solution Approach 1:
The invention changes the physical parameters of the sealing process by using a sealing solution with specific density (greater than the aqueous solution) and introducing surfactants to reduce surface tension. This allows beads to be sealed into arrays through density-driven separation rather than strong centrifugal force, dramatically reducing preparation time and enabling efficient sealing of millions of arrays
Solution Approach 2:
The invention introduces a sealing solution as an intermediary substance between the bead-containing aqueous solution and the array. This sealing solution, with its specific density and surfactant properties, acts as a mediator that enables gentle, efficient bead sealing without requiring strong external centrifugal force
2Measurement precision
If the number of arrays is increased to detect very low concentration target molecules, then detection sensitivity improves, but the time and effort required for array preparation increases significantly
Solution Approach 1:
By changing the density parameter of the sealing solution and using surfactants to modify surface properties, the invention enables rapid bead sealing that scales efficiently. This allows preparation of millions of arrays for high-sensitivity detection without the time penalty that would normally accompany increased array numbers
3Productivity
If strong centrifugal force is applied to seal beads into arrays, then bead sealing efficiency improves, but the complexity and requirements of the equipment increase
Solution Approach 1:
The invention replaces the strong mechanical centrifugal force system with a gentler density-driven separation mechanism. By using a sealing solution with specifically controlled density and surfactant properties, bead sealing is achieved through natural density stratification rather than strong mechanical centrifugal fields, simplifying equipment requirements
Solution Approach 2:
The invention changes the physical parameters of the sealing process by using a sealing solution with specific density (greater than the aqueous solution) and introducing surfactants to reduce surface tension. This allows beads to be sealed into arrays through density-driven separation rather than strong centrifugal force, dramatically reducing preparation time and enabling efficient sealing of millions of arrays
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 the efficient sealing of a large number of substances into arrays, enhancing the sensitivity of target molecule detection, particularly for low-concentration molecules like those found in 10 aM concentrations.
Implementation Method 1
introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent
Implementation Method 2
a step of introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent
Implementation Method 3
at least one of the first solvent and the second solvent contains a surfactant
Data Source
Figure 1A~1H
Figure 2
AI summary
As a technique for efficiently sealing many substances, such as beads, nucleic acid, protein, virus, cells, and lipid membrane complex, into an array, the present invention provides a method for sealing a substance, including: (i) a step of introducing a first solvent containing a substance on a substrate on which a plurality of receptacles capable of storing the substance are formed separated from each other by a side wall; and (ii) a step of introducing a second solvent having a greater specific gravity than that of the first solvent onto the first solvent, the step (ii) being carried out after the step (i).