LPS-Binding DNA Aptamers for Precise Gram-Negative Detection

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Solution Overview

Problem

Existing methods for detecting lipopolysaccharides (LPS) are not as efficient or cost-effective as they could be, and aptamers directed against LPS have not fully exploited the potential of in vitro synthesis and modification for high specificity and stability.

Innovation Solution

Development of DNA aptamers with specific loop and double-stranded stem structures, labeled with optical or electrochemical labels, capable of binding to LPS with high affinity and specificity, and their use in detection kits and assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If aptamers are synthesized in vitro to detect LPS, then manufacturing cost and batch consistency are improved, but detection precision and specificity may be compromised

Engineering Contradiction:

Improvemanufacturing cost and batch consistencyVSAvoiddetection precision and specificity

Core Design Contradiction:

Ease of manufactureVSMeasurement precision

Solution Approach 1:

The aptamer is divided into distinct functional regions: a binding region (15-25 nucleotides) that specifically recognizes LPS, a structural region that forms stable secondary structures (hairpins, bulges, loops), and a constant region for assay compatibility. This segmentation allows independent optimization of each function, ensuring both manufacturability and detection precision.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different regions of the aptamer are designed with specific local properties: the binding region contains sequences complementary to LPS components (lipid A, core polysaccharide, or O-antigen), the structural region incorporates G-quadruplexes or hairpin structures for stability, and the constant region provides uniformity for automated synthesis. This local differentiation enables the aptamer to achieve high specificity while maintaining ease of manufacture.

Inventive Principle:

Principle #3Local quality

2Measurement precision

If aptamers are designed with complex three-dimensional structures for high affinity binding, then binding specificity is improved, but structural stability under various temperatures may deteriorate

Engineering Contradiction:

Improvebinding specificityVSAvoidstructural stability at various temperatures

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The aptamer combines multiple structural motifs (G-quadruplexes, hairpins, internal loops) within a single nucleic acid sequence to create a composite structure that achieves both high binding specificity and thermal stability. The G-quadruplex regions provide rigid structural frameworks that maintain binding geometry across temperature variations, while flexible loops allow conformational adaptation for specific LPS recognition.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The aptamer sequence is designed with built-in structural cushions such as stacked base pairs, G-quadruplex planes, and hydrophobic cores that preemptively protect the three-dimensional structure from thermal denaturation. These pre-formed stable elements act as structural buffers that maintain binding capability across a wide temperature range, preventing loss of specificity under varying conditions.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Difficulty of detecting and measuring

If aptamers are modified with functional groups such as fluorescent molecules, then detection capability is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvedetection capabilityVSAvoidmanufacturing complexity

Core Design Contradiction:

Difficulty of detecting and measuringVSDevice complexity

Solution Approach 1:

The aptamer design incorporates a standardized constant region with universal properties that can accommodate various functional group attachments (fluorophores, quenchers, biotin, streptavidin) without affecting the binding region. This universal platform allows the same aptamer core to be used across multiple detection modalities (FRET, ELISA, lateral flow), simplifying manufacturing by reusing the validated binding sequence while only modifying the terminal functional groups.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 DNA aptamers provide stable and cost-effective detection of LPS, enabling accurate identification of Gram-negative bacteria, particularly in medical samples, with potential for rapid diagnosis and treatment of infections.

Implementation Method 1

Aptamers are short strands of oligonucleotides that form a three-dimensional structure able to bind a target material with high affinity and specificity

Methodology Applied

Scientific EffectMolecular recognition and binding:

Data Source

PatentUS12600972B2Lipopolysaccharide (LPS) aptamers and associated methods

Publication Date: 2026.04.14 FRESENIUS MEDICAL CARE HOLDINGS INC

AI summary

Described are a number of aptamers that are specific to bind with lipopolysaccharide (LPS), and associated methods.