Hairpin Probe Sensor for Nucleic Acid Detection

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Solution Overview

Problem

Point-of-care systems face challenges in detecting nucleic-acid sequences due to the need for labeled primers and limited rinsing and washing capabilities, leading to poor signal-to-noise ratios and potential false signals, especially in mobile and portable settings.

Innovation Solution

A sensor apparatus using hairpin probes bonded to a surface, which can hybridize with target nucleic-acid sequences without labeled primers, improving signal-to-noise ratio and allowing for real-time PCR without additional labeling steps, enabling precise detection of nucleic-acid sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If labeled primers are used for PCR to detect nucleic-acid sequences, then detection capability is achieved, but device complexity and detection precision deteriorate due to additional PCR steps and poor signal-to-noise ratio

Engineering Contradiction:
Improvedetection precisionVSAvoidcomplexity of detection process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the need for labeled primers from the detection system. By using unlabeled primers for PCR amplification and instead labeling the capture molecules on the sensor surface, the system removes the complex step of incorporating labels during PCR while maintaining detection capability through hybridization-based detection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention inverts the conventional approach by placing the label on the capture molecule rather than on the primer. This reversal allows unlabeled PCR primers to amplify the target, which then hybridizes to labeled capture molecules on the sensor surface, improving signal-to-noise ratio by ensuring labels are only present where hybridization occurs.

Inventive Principle:
Principle #13The other way round (Inversion)

2Reliability

If labeled target nucleic-acid sequences are immobilized on capture molecules for separation, then specific detection is achieved, but measurement precision deteriorates due to erroneous signals and poor signal-to-noise ratio

Engineering Contradiction:
Improvedetection reliabilityVSAvoidsignal-to-noise ratio
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The invention performs preliminary labeling of capture molecules on the sensor surface before the detection process. This allows unlabeled PCR amplification to occur first, followed by hybridization of the amplified product to the pre-labeled capture molecules, ensuring that labels are only present on successfully hybridized targets and eliminating background noise from free labels.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If microfluidic systems are used in point-of-care systems for automated processing, then ease of operation is improved, but measurement precision deteriorates due to limited rinsing and washing capabilities

Engineering Contradiction:
Improveautomation capabilityVSAvoidsignal-to-noise ratio
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention employs a disposable sensor cartridge that integrates the sensor apparatus with all necessary reagents including pre-labeled capture molecules. This single-use design eliminates the need for complex rinsing and washing systems by ensuring that all labeling occurs during the controlled hybridization step, while the disposable nature maintains automation compatibility for point-of-care applications.

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

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 enhances detection sensitivity and reduces errors by eliminating the need for labeled primers and additional PCR steps, allowing for accurate identification of nucleic-acid sequences in point-of-care systems, even in mobile settings.

Implementation Method 1

A sensor apparatus using hairpin probes bonded to a surface, which can hybridize with target nucleic-acid sequences

Methodology Applied
Scientific EffectHybridization: Chemical Bonding

Data Source

PatentUS11268134B2Sensor apparatus and method for testing a sample
Publication Date: 2022.03.08 BOEHRINGER INGELHEIM VETMEDICA GMBH
  • US11268134B2 patent drawing
  • US11268134B2 patent drawing
  • US11268134B2 patent drawing

AI summary

A sensor apparatus for testing a biological sample, a system making use thereof and a method for testing a biological sample with the sensor apparatus and system.