SWCNT Molecular Tool for Label-Free miRNA Detection

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Solution Overview

Problem

Current methods for detecting microRNAs (miRNAs) face challenges such as trade-offs between accuracy/sensitivity and cost/time, with RNA-sequencing being sensitive but time-consuming and costly, and RT-PCR being prone to errors and lacking reproducibility, while existing optical sensors require surfactants that can be toxic and affect bioenvironment.

Innovation Solution

A label-free method using a molecular tool comprising a substrate of optical material, such as Single Wall Carbon Nanotubes (SWCNTs), coupled with nucleic acid analogues like PNA, which allows for direct optical detection of miRNAs without the need for surfactants, enabling rapid and specific detection through nucleobase complementarity and electromagnetic radiation interaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If RNA-sequencing is used for miRNA detection, then sensitivity and accuracy are improved, but processing time and cost increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts and eliminates the need for reverse-transcription and amplification steps from the detection workflow. By using a label-free optical detection method that directly detects miRNA hybridization events, the invention removes time-consuming processing steps while maintaining high sensitivity through direct optical signal transduction from the hybridization event.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/chemical amplification processes (reverse-transcription and PCR) with an optical detection system based on SWCNT fluorescence. This substitution eliminates the need for complex enzymatic reactions and thermal cycling, dramatically reducing processing time while maintaining detection sensitivity through direct optical transduction of hybridization events.

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

2Productivity

If RT-PCR is used for miRNA detection, then processing time is reduced, but specificity and reproducibility deteriorate due to errors in reverse-transcription and background corrections

Engineering Contradiction:
Improveprocessing speedVSAvoidreproducibility
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent removes the reverse-transcription step entirely from the detection process. By using a label-free optical method that directly detects miRNA hybridization to the probe on SWCNTs, the invention eliminates the source of reproducibility errors associated with reverse-transcription efficiency variations and background correction requirements, while maintaining rapid processing.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The SWCNT-based optical sensor performs self-detection of hybridization events through intrinsic fluorescence changes. The system requires no external labels, enzymes, or amplification reagents, eliminating the need for complex background corrections and standardization protocols, thereby improving reproducibility while maintaining fast processing.

Inventive Principle:
Principle #25Self-service

3Productivity

If existing optical sensors using SWCNTs are used for miRNA detection, then detection speed is improved, but toxicity and bioenvironment interference occur due to surfactant requirements

Engineering Contradiction:
Improvedetection speedVSAvoidtoxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and eliminates the requirement for surfactants from the detection system. By using a label-free optical detection method where miRNA hybridization directly modulates SWCNT fluorescence, the invention removes the need for surfactant molecules that cause toxicity and bioenvironment interference, enabling safe in vivo applications while maintaining rapid detection capability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The SWCNT probe performs self-detection of miRNA through intrinsic fluorescence changes upon hybridization. This self-service mechanism eliminates the need for external surfactants or labels, removing the source of toxicity while preserving the rapid detection speed through direct optical transduction of the hybridization event.

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

This approach provides a robust, customizable, and purification-free platform for detecting miRNAs, offering improved sensitivity and specificity without the need for surfactants, making it suitable for in vivo applications and point-of-care diagnostics.

Implementation Method 1

spectral changes in the emission spectrum of the SWCNT

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Optical modulation of SWCNT fluorescence was first used to detect DNA hybridization

Methodology Applied
Scientific EffectOptical modulation:

Implementation Method 3

providing an electromagnetic radiation to the sample comprising the molecular tool under conditions allowing the interaction of the electromagnetic radiation with the optical material

Methodology Applied
Scientific EffectElectromagnetic radiation interaction:

Data Source

PatentUS20250002979A1A Molecular Tool And Use Thereof In A Label-Free Method For Detecting A Target Nucleic Acid In A Sample
Publication Date: 2025.01.02 ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
  • US20250002979A1 patent drawing
  • US20250002979A1 patent drawing
  • US20250002979A1 patent drawing

AI summary

A molecular tool and a label-free method useful for detecting a target nucleic acid in a sample are disclosed, the molecular tool comprising a substrate comprising or consisting of an optical material; a first polymeric molecule, selected from nucleic acids or nucleic acid analogues, coupled with the substrate; and a second nucleic acid analogue coupled with the first polymeric molecule by means of nucleobase complementarity. The molecular tools and methods of the invention are configured for the optical detection of oligonucleotide binding events for diagnostic, point-of-care, drug screening applications using for instance a carbon nanotube optical signal. Circulating nucleic acids that have diagnostic and prognostic value for cancer, metabolic disease, organ rejection, foetal health and infectious disease can be therefore identified and characterized.