Multiplex Microfluidic Device for Parallel Aptamer Selection

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Solution Overview

Problem

Current methods for selecting nucleic acid aptamers are time-consuming, complex, and not suitable for multiplexed selection, as they primarily isolate aptamers for single targets, requiring extensive repetition and lacking automation for simultaneous isolation of multiple aptamers.

Innovation Solution

A multiplex microfluidic device with a substrate having binding channels, target molecule-binding regions, elution channels, and a valve on/off system, allowing for simultaneous selection and automation of aptamers for multiple targets through a high-throughput process that includes introducing nucleic acids, binding, elution, amplification, and repeated cycles without final amplification, enabling efficient selection and sequencing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional SELEX process is used for single target, then aptamers can be isolated with high affinity, but the process requires large amount of time and is complicated

Engineering Contradiction:
Improveaptamer isolation effectivenessVSAvoidprocess time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The device divides the binding channel into multiple target molecule-binding regions (first, second, third regions) that can simultaneously bind different target molecules. This segmentation allows parallel processing of multiple aptamer selections, reducing the overall time required while maintaining the effectiveness of each individual selection process

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention merges multiple SELEX processes into a single integrated device. Multiple target molecules are bound simultaneously in different regions of the same device, and a single pool of nucleic acids is introduced to interact with all targets concurrently, combining what would traditionally require multiple separate experiments into one unified process

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If conventional SELEX process is used, then aptamers can be selected, but the process is complicated and requires extensive repetition

Engineering Contradiction:
Improveaptamer selection capabilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The device is designed as a universal platform that can simultaneously perform multiple aptamer selection processes for different target molecules using a single pool of nucleic acids. The binding channel with multiple target-binding regions allows the same device structure to handle diverse selection experiments, reducing the need for multiple specialized devices and simplifying the overall workflow

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention transitions from sequential single-target selection to parallel multi-target selection by adding spatial dimensionality to the process. Multiple target molecules are positioned in different spatial regions (first, second, third binding regions) within the same device, allowing simultaneous interaction with the nucleic acid pool and enabling multiplexed selection without increasing procedural complexity

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

3Loss of time

If previous microfluidic device is used, then SELEX process time is shortened, but several aptamers cannot be simultaneously isolated and only sequential isolation is possible

Engineering Contradiction:
ImproveSELEX process timeVSAvoidmultiplexed selection capability
Core Design Contradiction:
Loss of timeVSAdaptability or versatility

Solution Approach 1:

The binding channel is segmented into multiple distinct target molecule-binding regions, each capable of independently binding different target molecules. This segmentation enables simultaneous isolation of multiple aptamers in parallel, overcoming the limitation of sequential processing while maintaining the time-efficient microfluidic approach

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The device utilizes spatial arrangement of multiple binding regions within the microfluidic channel to enable multiplexed selection. By positioning first, second, and third target-binding regions at different locations along the channel, the system achieves parallel processing capability, allowing simultaneous isolation of multiple aptamers rather than sequential processing

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

4Loss of time

If previous microfluidic device is used, then process time is reduced, but means for isolating aptamers are limited and automation is not achieved

Engineering Contradiction:
Improveisolation timeVSAvoidprocess automation level
Core Design Contradiction:
Loss of timeVSExtent of automation

Solution Approach 1:

The device is designed as a universal platform that can handle multiple target molecules and aptamer selections simultaneously through a standardized binding channel structure with multiple target-binding regions. This universality enables integration with automated liquid handling systems and high-throughput sequencing platforms, facilitating automation of the entire workflow from sample introduction to data analysis

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

The device enables the simultaneous isolation of aptamers for numerous targets in a significantly shorter time, increasing throughput and automating the process, reducing the need for extensive repetition and manual handling, and facilitating high-throughput sequencing for rapid aptamer selection and analysis.

Implementation Method 1

a pool of nucleic acids is introduced into the binding channel to bind to target molecules in target molecule-binding regions

Methodology Applied
Scientific EffectBinding interaction: Adsorption

Data Source

PatentUS10221412B2Multiplex microfluidic device for selecting nucleic acid aptamers, and high throughput selection method for nucleic acid aptamers using same
Publication Date: 2019.03.05 PCL
  • US10221412B2 patent drawing
  • US10221412B2 patent drawing
  • US10221412B2 patent drawing

AI summary

The present invention relates to a multiplex microfluidic device for selection of nucleic acid aptamers and a method for high-throughput selection of nucleic acid aptamers using the same, and more particularly to a multiplex microfluidic device (SELEX lap-on-a-chip) that uses an improved multiplex platform in place of the development of an aptamer for a single target and to a method for high throughput selection of aptamers using the same together with high-throughput sequencing. A multiplex microfluidic device according to the present invention can simultaneously detect aptamers for a plurality of targets, and it can greatly increase the screening throughput and greatly shorten the process time compared to conventional multiplex techniques. Particularly, when a process for selecting aptamers is performed using the device of the invention together with a high-throughput sequencing method, the number of target binding/elution/amplification rounds can be greatly reduced, and the process can be performed in an automated manner. Thus, the device of the invention is highly useful.