Multiplexed Microcolumn Devices for Aptamer Selection
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Solution Overview
Problem
Current affinity chromatography-based methods for selecting nucleic acid aptamers are inefficient and labor-intensive, particularly when dealing with multiple targets, as they require large resin volumes, are expensive, and lack high-throughput capabilities.
Innovation Solution
The development of reconfigurable microcolumn devices that use minimal affinity chromatography resin (2-50 μL) and can be easily assembled in various configurations for serial or parallel operations, allowing for efficient selection of aptamers for single and multiple targets, and integration with common laboratory equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If affinity chromatography-based methods are used for selecting nucleic acid aptamers, then high purification quality (>95%) can be achieved, but large resin volumes are required and the process becomes labor-intensive
Solution Approach 1:
The invention divides the affinity chromatography system into multiple microcolumns (each containing 2-50 μL resin) that can be connected in series or parallel configurations. This segmentation allows the same purification quality to be achieved through multiple small columns working together, rather than requiring a single large column, thereby reducing the resin volume required in each individual column while maintaining overall system performance.
Solution Approach 2:
The invention transitions from a single-column affinity chromatography system to a multi-column system with configurable serial and parallel arrangements. This dimensional change in system architecture enables flexible scaling where multiple microcolumns can be combined to achieve the required purification quality without increasing the resin volume in each column, thus resolving the contradiction between purification quality and resin volume requirements.
2Adaptability or versatility
If standard affinity chromatography columns are used for multiple target selection, then comprehensive screening can be performed, but the cost increases due to higher resin and target immobilization requirements
Solution Approach 1:
The invention segments the multi-target screening function across multiple independent microcolumns, each containing a small amount of resin (2-50 μL) with a specific target immobilized. This segmentation allows comprehensive multi-target screening capability while minimizing the resin and target material required in each column, as each microcolumn handles a specific target rather than requiring one large column to handle all targets.
Solution Approach 2:
The microcolumn system provides universal functionality by enabling the same basic microcolumn design to be used for single or multiple target selections through configurable serial and parallel arrangements. The system can be adapted to screen for any number of targets by simply connecting the appropriate number of microcolumns, thereby achieving multi-target screening capability without proportionally increasing resin and material requirements.
3Ease of operation
If batch-mode affinity chromatography is used, then simple operation is possible, but the process is labor-intensive and time-consuming when repeated multiple times
Solution Approach 1:
The invention merges multiple batch-mode affinity chromatography operations into a single continuous flow process by connecting multiple microcolumns in series. The library flows continuously through all columns simultaneously, performing multiple selection operations in one pass rather than requiring sequential batch operations. This maintains the simplicity of batch operation while dramatically improving productivity by eliminating repeated manual steps.
Solution Approach 2:
The invention transforms the discontinuous batch-mode process into a continuous flow process where the nucleic acid library continuously flows through the series of microcolumns. This continuous action allows multiple selection operations to occur simultaneously in one continuous pass, eliminating the need to stop, process, and restart between operations, thereby maintaining ease of operation while significantly improving selection process efficiency.
4Extent of automation
If flow-mode affinity chromatography with small columns is used, then automation is possible, but more resin and immobilized target are required compared to batch-mode
Solution Approach 1:
The invention segments the flow-mode affinity chromatography system into multiple microcolumns, each requiring only 2-50 μL of resin. This segmentation allows automation to be implemented with small, manageable column units that require minimal resin and target material each, while the overall system achieves comprehensive screening capability through the combined effect of multiple columns connected in series or parallel.
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
Facilitates high-throughput and efficient aptamer selection by reducing resin requirements, enabling rapid screening for multiple targets with improved specificity and affinity, and allowing for real-time monitoring and optimization of the selection process.
Implementation Method 1
a frit disposed in the recessed portion
Implementation Method 2
each adapter includes a connector region for effectuating serial fluid communication of a plurality of microcolumn devices
Implementation Method 3
affinity chromatography resin disposed in the microfluidic channel of the body
Implementation Method 4
introducing a sample comprising a population of nucleic acid molecules through the serially connected microcolumn devices under conditions effective to allow nucleic acid molecules to bind specifically to the target molecules
Data Source
AI summary
The present invention relates to a microcolumn device for selecting nucleic acid aptamers for single and multiple target molecules, as well as a method for making the microcolumn device. The present invention also relates to a system for selecting nucleic acid aptamers for single and multiple target molecules. The present invention further relates to methods of using the microcolumn device for selecting nucleic acid aptamers for multiple target molecules. Kits that include one or more microcolumn device and/or system of the present invention are also disclosed.