Micro-fluidic Isolation Pens for Specific Nucleic Acid Capture

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for extracting and selectively capturing nucleic acid materials from biological cells are inefficient and lack specificity, often resulting in contamination and mixed nucleic acid types within micro-fluidic devices.

Innovation Solution

A micro-fluidic device with isolation pens and capture objects that utilize specific binding materials to selectively capture nucleic acid types from individual biological cells, allowing for precise identification and correlation of captured nucleic acid material with its origin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current extraction methods are used, then nucleic acid materials can be obtained from biological cells, but the extraction is inefficient and lacks specificity resulting in contamination and mixed nucleic acid types

Engineering Contradiction:
Improvespecificity of nucleic acid captureVSAvoidextraction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The device segments the extraction process into distinct functional zones: isolation pens for individual cell containment, lysis zones for controlled cell breakdown, and capture regions with specific binding materials. This spatial segmentation enables simultaneous processing of multiple cells with different nucleic acid types without cross-contamination, thereby improving both specificity and efficiency

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the micro-fluidic device are equipped with capture materials having different specificities tailored to local requirements. For example, certain isolation pens contain capture materials specific to DNA while others contain materials specific to RNA or organelle membranes. This local differentiation of capture properties enables highly specific extraction of desired nucleic acid types while maintaining high throughput

Inventive Principle:
Principle #3Local quality

2Reliability

If conventional extraction methods are used, then nucleic acid materials can be extracted from cells, but contamination and mixed nucleic acid types occur

Engineering Contradiction:
Improvepurity of captured nucleic acidVSAvoidcomplexity of isolation and capture system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The device employs a nested structure where multiple isolation pens are integrated within a single micro-fluidic chip, each pen containing its own capture objects. This nesting approach allows parallel processing of multiple samples in a compact footprint, achieving high purity through physical isolation while avoiding the need for complex external equipment or multi-step procedures

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

Capture objects serve as intermediary elements between the lysed cell contents and the final nucleic acid product. These capture objects with specific binding materials selectively bind to target nucleic acids, facilitating pure separation from non-target materials. The capture objects can then be easily removed or retained based on downstream application needs

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If individual cells are processed separately, then specific nucleic acid types can be captured, but the process requires precise correlation between capture objects and originating cells

Engineering Contradiction:
Improvecorrelation accuracy between capture objects and cellsVSAvoidthroughput of cell processing
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The device establishes correlation between capture objects and originating cells before the actual capture process. Isolation pens are pre-configured with specific capture materials and pre-associated with identification markers or positional information. When cells are introduced and lysed, the capture objects are already in position to selectively bind specific nucleic acid types, and the correlation data is already recorded, enabling high-throughput processing with precise tracking

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

Enables efficient and specific extraction of nucleic acid materials, preventing contamination and allowing for accurate correlation of captured nucleic acids with their originating cells, enhancing the precision and reliability of nucleic acid analysis.

Implementation Method 1

Each of the capture objects can comprise a capture material that binds to a particular type of nucleic acid material with at least two times greater specificity than it binds to other types of nucleic acid material

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Data Source

PatentUS11318479B2Capturing specific nucleic acid materials from individual biological cells in a micro-fluidic device
Publication Date: 2022.05.03 BRUKER SPATIAL BIOLOGY INC
  • US11318479B2 patent drawing
  • US11318479B2 patent drawing
  • US11318479B2 patent drawing

AI summary

Individual biological cells can be selected in a micro-fluidic device and moved into isolation pens in the device. The cells can then be lysed in the pens, releasing nucleic acid material, which can be captured by one or more capture objects in the pens. The capture objects with the captured nucleic acid material can then be removed from the pens. The capture objects can include unique identifiers, allowing each capture object to be correlated to the individual cell from which the nucleic acid material captured by the object originated.