Microfluidic Glycan Analysis Device

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Solution Overview

Problem

Traditional methods for glycan analysis from glycoproteins are time-consuming, cumbersome, and require large quantities of starting material, with manual operations being error-prone and inefficient.

Innovation Solution

A microfluidic device with a deglycosylation column, trapping column, and separation column, utilizing a switching element to streamline the process, allowing for rapid deglycosylation, enrichment, and separation of glycans, achieving higher recovery yields and superior chemical separation of isoforms with a significantly smaller sample amount.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional in-solution enzymatic reaction with PNGase F is used for glycan removal, then glycan analysis can be performed, but the process requires 24-hour incubation time and multiple manual steps

Engineering Contradiction:
Improveglycan analysis qualityVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces traditional manual mechanical operations (pipetting, centrifugation, filtration) with an automated microfluidic system that integrates enzymatic deglycosylation, protein precipitation, and glycan separation in a continuous flow process, eliminating the need for 24-hour incubation and multiple manual transfer steps while maintaining analytical quality

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent combines multiple separate operations (enzymatic reaction, protein precipitation, glycan separation) into a single integrated microfluidic device where samples flow continuously through different functional zones, allowing all steps to occur simultaneously in sequence rather than as separate time-consuming operations

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If traditional manual operations are used for glycan processing, then glycan separation can be achieved, but the process is error-prone and cumbersome

Engineering Contradiction:
Improveglycan separation qualityVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces error-prone manual pipetting and handling with an automated microfluidic system that uses integrated pumps, valves, and channels to precisely control sample flow through deglycosylation and separation zones, eliminating human error while maintaining separation quality

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The microfluidic device is designed to perform all operations autonomously once sample is loaded - the system self-regulates flow rates, mixing, enzymatic reaction conditions, and separation parameters without requiring operator intervention at each step, making operation simple and reproducible

Inventive Principle:
Principle #25Self-service

3Measurement precision

If traditional methods are used for glycan analysis, then sufficient data can be obtained, but a relatively large quantity of starting material is required

Engineering Contradiction:
Improvedata qualityVSAvoidstarting material amount
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent changes the physical parameters of the system by miniaturizing all dimensions - channel widths, chamber volumes, and flow rates are reduced to micro-scale, which increases surface-to-volume ratios and enhances mass transfer efficiency, allowing high-quality data to be obtained from minimal sample quantities that would be insufficient in traditional macro-scale systems

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If multiple separate steps are used for glycan analysis, then thorough processing can be achieved, but the device complexity and manual operations increase

Engineering Contradiction:
Improveprocessing thoroughnessVSAvoidsystem structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple separate processing steps into a single integrated microfluidic chip where deglycosylation columns, separation columns, and detection zones are connected through microchannels, allowing thorough processing to occur in a compact unified device rather than through multiple separate instruments and manual transfers

Inventive Principle:
Principle #5Merging (Combining)

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 microfluidic device enables fast and efficient glycan analysis, achieving higher recovery yields and superior chemical separation of isoforms, reducing analysis time to minutes and requiring a significantly smaller sample amount compared to traditional methods.

Implementation Method 1

The process of removing glycans from glycoproteins traditionally includes an in-solution enzymatic reaction with PNGase F

Methodology Applied
Scientific EffectEnzymatic hydrolysis: Enzyme

Implementation Method 2

After the enzyme reaction, protein precipitation is needed to separate the glycans from the proteins for analysis of the glycans

Methodology Applied
Scientific EffectProtein precipitation: Precipitation

Data Source

PatentUS10209259B2Microfluidic glycan analysis
Publication Date: 2019.02.19 AGILENT TECHNOLOGIES INC
  • US10209259B2 patent drawing
  • US10209259B2 patent drawing
  • US10209259B2 patent drawing

AI summary

Microfluidic devices and methods for analyzing glycan profiles of glycoproteins are provided. Some embodiments of the devices comprise a deglycosylation column for cleaving glycans, an optional cleaning column for removing proteins, a trapping column for enriching glycans, and a separation column for resolving glycans. The devices and methods significantly improve the speed and sensitivity of glycan analysis.