Hemoglobin A1c Aptamer Detection via SELEX Microfluidics

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Solution Overview

Problem

Current methods for detecting hemoglobin A1c in diabetes diagnosis are plagued by high costs, the need for sophisticated equipment, long processing times, and the instability of antibodies used in immunoassays, leading to inaccurate and unreliable results.

Innovation Solution

Development of specific aptamers that bind to hemoglobin A1c, which are nucleic acid molecules with defined sequences, used in microfluidic chips for accurate detection, overcoming the limitations of traditional antibody-based methods by providing high specificity, thermal stability, and ease of synthesis and storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibody-based immunoassay methods are used for HbA1c detection, then detection capability is achieved, but cost increases and reliability decreases due to antibody instability and batch variability

Engineering Contradiction:
Improvedetection reliabilityVSAvoidmanufacturing cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces antibodies with aptamers (nucleic acid molecules) that copy the binding function of antibodies. Aptamers are synthesized through in vitro selection (SELEX) to bind specifically to HbA1c, providing a stable, reproducible alternative to protein-based antibodies while reducing cost and batch variability.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent uses aptamers that can be synthesized cheaply through chemical methods rather than expensive biological production of antibodies. The aptamers are designed as single-use or limited-use reagents that can be discarded after use, eliminating the need for expensive storage infrastructure and quality control of antibody batches.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Measurement precision

If traditional HbA1c detection methods (HPLC) are used, then accurate measurement is achieved, but processing time increases and device complexity increases

Engineering Contradiction:
ImproveHbA1c measurement accuracyVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the essential detection function from complex HPLC systems by using aptamer-based binding followed by simple detection methods. The aptamer-HbA1c complex can be detected through various means (electrochemical, optical, etc.) that require minimal equipment, removing the need for sophisticated chromatography systems while maintaining measurement accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/chromatographic separation process of HPLC with molecular recognition-based detection using aptamers. The specific binding between aptamer and HbA1c provides the separation and detection function, eliminating the need for complex mechanical pumping, column separation, and data processing systems.

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

3Reliability

If antibody-based methods are used for HbA1c detection, then detection function is provided, but storage and transport become difficult due to antibody sensitivity to environmental conditions

Engineering Contradiction:
Improvedetection stabilityVSAvoidstorage and transport convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces temperature-sensitive protein antibodies with nucleic acid aptamers that have superior thermal and chemical stability. Aptamers can be stored at room temperature or frozen without denaturation, and are not affected by proteases or pH variations that degrade antibodies, enabling easy storage and transport without specialized infrastructure.

Inventive Principle:
Principle #26Copying

4Ease of operation

If manual antibody operations are used, then detection is performed, but human error increases and operational complexity increases

Engineering Contradiction:
Improveoperational simplicityVSAvoidoperational accuracy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent designs aptamer-based detection systems that minimize manual intervention. The aptamers can be pre-loaded into devices, automatically bind to HbA1c in the sample, and generate detectable signals with minimal human handling. This self-service approach reduces opportunities for human error while maintaining operational simplicity.

Inventive Principle:
Principle #25Self-service

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 aptamers enable precise and cost-effective detection of hemoglobin A1c, offering improved accuracy and reliability compared to existing methods, with the ability to replace antibodies and provide stable, reusable solutions for diabetes monitoring.

Implementation Method 1

an aptamer specifically binds to hemoglobin A1c, wherein the aptamer is a nucleic acid molecule comprising at least a nucleic acid sequence of SEQ ID NO: 1

Methodology Applied
Scientific EffectMolecular recognition:

Implementation Method 2

an aptamer specifically binds to hemoglobin, wherein the aptamer is a nucleic acid molecule comprising at least a nucleic acid sequence of SEQ ID NO: 5

Methodology Applied
Scientific EffectMolecular recognition:

Data Source

PatentUS9086406B2Hemoglobin A1c-specific aptamer, hemoglobin-specific aptamer, and applications thereof
Publication Date: 2015.07.21 NATIONAL TSING HUA UNIVERSITY
  • US9086406B2 patent drawing
  • US9086406B2 patent drawing
  • US9086406B2 patent drawing

AI summary

The present invention provides a Hemoglobin A1c-specific aptamer and a Hemoglobin-specific aptamer. The aptamers were selected in vitro using SELEX and a microfluidic chip system. The aptamers established low free energy, thus were more stable than conventional antibodies. The high specificity of the aptamers to Hemoglobin A1c or Hemoglobin allows them to be effectively used in diagnosis of diabetes and/or anemia.