Particle Capture Well Arrays for mRNA Leakage Control

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Solution Overview

Problem

Existing single cell capture systems face issues with non-specific capture and leakage of target material such as mRNA and proteins, particularly in microfluidic devices, leading to inefficiencies in cell processing and analysis.

Innovation Solution

A method involving the use of an array of wells on a substrate where target cells and particles are received, with particles retained closer to the surface than cells, followed by washing with a fluid reservoir, applying a lysis buffer at controlled temperatures, and using a partitioning fluid to retain mRNA within the wells while controlling heat transmission.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If particles and cells are co-captured in the same wells, then capture efficiency is improved, but non-specific capture increases

Engineering Contradiction:

Improvecapture efficiencyVSAvoidspecific capture

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent introduces a vertical dimension to particle-cell separation by establishing distinct retention zones within the well: particles are retained closer to the surface plane while cells are retained deeper in the well. This vertical stratification allows both particles and cells to be captured in the same well (improving efficiency) while preventing non-specific capture (maintaining precision) through spatial separation along the vertical axis.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The well is segmented into different functional zones: a particle retention zone near the surface and a cell retention zone deeper in the well. This segmentation allows independent control over particle and cell positions, enabling efficient co-capture while minimizing non-specific interactions through physical separation of the two target materials within the same well.

Inventive Principle:

Principle #1Segmentation

2Quantity of substance

If target material is captured across multiple chambers, then capture capacity is improved, but leakage between chambers increases

Engineering Contradiction:

Improvecapture capacityVSAvoidleakage control

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent introduces a partitioning fluid as an intermediary substance between adjacent wells to prevent leakage of target material. This partitioning fluid creates a physical barrier that isolates captured cells and particles in each well, allowing the system to expand capture capacity across multiple chambers while maintaining reliable containment through the intermediary partitioning medium.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If lysis buffer is applied at higher temperature, then cell lysis efficiency is improved, but mRNA degradation increases

Engineering Contradiction:

Improvelysis efficiencyVSAvoidmRNA integrity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent utilizes controlled temperature phase transitions to optimize the lysis process. By carefully controlling the temperature during lysis buffer application, the system achieves efficient cell membrane disruption (lysis) while preventing excessive thermal energy that would cause mRNA degradation. The temperature control enables the system to operate in an optimal phase range where lysis is effective but mRNA remains intact.

Inventive Principle:

Principle #36Phase transitions

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 approach minimizes non-specific capture and leakage, enabling efficient cell processing and retention of mRNA, facilitating downstream assays and maintaining cell viability.

Implementation Method 1

displacing the air within the cavity with a partitioning fluid, comprising oil; and retaining messenger ribonucleic acid (mRNA) material of the set of target cells, within the array of wells

Methodology Applied

Scientific EffectSurface tension: Surface Tension

Implementation Method 2

retaining messenger ribonucleic acid (mRNA) material of the set of target cells, within the array of wells, with transmission of heat into the array of wells

Methodology Applied

Scientific EffectHeat conduction: Conduction (thermal)

Implementation Method 3

receiving a washing fluid into a reservoir in communication with the array of wells, thereby washing off excess particles

Methodology Applied

Scientific EffectFluid flow:

Implementation Method 4

receiving a lysis buffer into the reservoir at a temperature of below 15°C

Methodology Applied

Scientific EffectTemperature control:

Data Source

PatentEP3956473B1Method for leakage control in a particle capture system

Publication Date: 2025.10.01 BIO RAD LABORATORIES INC

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Figure 3

AI summary

A system and method for target material capture, the method comprising: receiving a set of target cells into an array of wells defined at a surface plane of a substrate; receiving a set of particles into the array of wells, thereby co-capturing the set of target cells and the set of particles; achieving a desired state for the array of wells upon receiving a washing fluid into a cavity in communication with the array of wells; receiving a lysis buffer into the cavity; receiving a partitioning fluid into the cavity, thereby displacing the lysis buffer from the cavity and partitioning each of the array of wells from adjacent wells, at the surface plane; and retaining intercellular material of the set of target cells, individually with the set of particles within the array of wells.