Slanted Nanofilter Array for Continuous Protein Separation
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Solution Overview
Problem
Existing protein sorting technologies face limitations such as low separation resolution, low sensitivity, and complexity in manufacturing and use, particularly due to the need for polymeric sieving matrices and batch-process orientation, which hinder continuous monitoring and portability in pharmaceutical manufacturing.
Innovation Solution
A nanofluidic chip with slanted nanofilter arrays featuring periodically-patterned deep and shallow nanochannels for protein preconcentration and size-based separation, enabling continuous monitoring and high detection sensitivity through a one-step process, eliminating the need for launching bands and reducing sample volume requirements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If SEC (Size Exclusion Chromatography) is used for protein separation, then protein purity can be checked, but separation resolution is low and sensitivity is low due to adsorption to polymeric sieving matrices
Solution Approach 1:
The patent removes the polymeric sieving matrix from the separation system entirely, replacing it with a microfluidic chip-based nanofilter array that uses size-based filtration without polymeric materials, thereby eliminating adsorption issues while maintaining separation capability
Solution Approach 2:
The patent replaces the mechanical chromatography system with a microfluidic system that uses electrokinetic forces and size-based nanofiltration to achieve separation, substituting the polymeric matrix mechanism with a controlled fluidic and electrical field mechanism
2Measurement precision
If gel electrophoresis is used for protein separation, then separation resolution is improved, but technical complexity increases due to polymeric sieving matrices and batch-process orientation
Solution Approach 1:
The patent extracts and removes the complex polymeric gel matrix from the electrophoresis system, replacing it with a simple microfluidic chip containing nanofilter arrays, thereby maintaining high separation resolution while dramatically reducing manufacturing and operational complexity
Solution Approach 2:
The patent changes the fundamental operating parameters from batch-process gel electrophoresis to continuous-flow microfluidic nanofiltration, enabling real-time monitoring while maintaining separation performance and simplifying the system
3Measurement precision
If batch-process oriented technologies are used for protein analysis, then protein separation can be achieved, but continuous throughput and real-time monitoring are not enabled
Solution Approach 1:
The patent transforms the static batch-process system into a dynamic continuous-flow system where samples are continuously introduced, separated, and monitored in real-time, enabling both high productivity and real-time quality control
Solution Approach 2:
The patent implements continuous operation by eliminating the batch-wise processing steps, allowing samples to flow continuously through the nanofilter array with real-time detection, thereby enabling continuous throughput and real-time monitoring simultaneously
4Quantity of substance
If existing nanofilter arrays are used for protein separation, then protein preconcentration can be achieved, but detection sensitivity is low due to short optical path lengths and device complexity
Solution Approach 1:
The patent extends the optical detection path length by utilizing the vertical dimension of the microfluidic channel, allowing light to traverse a longer path through the concentrated protein sample, thereby significantly improving detection sensitivity while maintaining the preconcentration capability
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 solution achieves rapid protein preconcentration and high separation resolution, enhancing detection sensitivity and allowing for continuous monitoring, making it suitable for real-time release and on-site drug purity testing.
Implementation Method 1
size-based separation of proteins using technologies such as Size Exclusion Chromatography (SEC) and SDS-PAGE
Implementation Method 2
slanted nanofilter arrays comprising periodically-patterned deep and shallow nanochannels, or nanoslits, are used to achieve protein preconcentration and size-based protein separation
Data Source
AI summary
This disclosure provides an apparatus and a method for quickly, efficiently and continuously fractionating biomolecules, such as DNAs and proteins based on size and other factors, while allowing imaging of the separated biomolecules as they are processed within the apparatus. The apparatus employs angled nanochannels to first preconcentrate and then separate like molecules. Its embodiments offer improved detection sensitivity and separation resolution over existing technologies and multiplexing capabilities.