Nucleic Acid Sequencing via Time-Resolved Luminescence

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Solution Overview

Problem

Current bioassays for detecting and analyzing biological samples require expensive equipment and trained personnel, and are often performed in bulk, making them inefficient for rapid and precise analysis of small sample quantities.

Innovation Solution

The method identifies single molecules based on luminescent intensity and lifetime, using luminescently labeled nucleotides with different spectral properties to differentiate between nucleotides, allowing for the determination of nucleic acid sequences through the detection of luminescence patterns.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional luminescent detection methods are used with laser light sources and complicated optics, then detection capability is achieved, but device complexity and cost increase

Engineering Contradiction:
Improvedetection capabilityVSAvoiddetection optics and electronics
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the complicated luminescent detection optics and electronics from the system. By using a simplified detection approach that relies on basic photodetector technology rather than complex optical systems, the invention achieves detection capability while significantly reducing device complexity and cost.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces expensive, complex, and durable optical components with simpler, more affordable detection elements. The use of basic photodetectors and simplified optics represents a shift toward more economical components that can be easily replaced or upgraded without significant investment.

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

2Measurement precision

If bulk sample analysis is performed, then detection is achieved, but sample quantity requirements increase and analysis efficiency decreases

Engineering Contradiction:
Improvedetection capabilityVSAvoidsample quantity
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention segments the analysis process to enable single-molecule or single-cell level detection. By developing detection methods that can identify and analyze individual biological entities rather than requiring bulk samples, the patent dramatically reduces the quantity of sample material needed while maintaining or improving detection precision.

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If trained personnel operate complex equipment, then accurate bioassays are performed, but operational complexity and training requirements increase

Engineering Contradiction:
Improvebioassay accuracyVSAvoidoperational complexity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention enables bioassays to perform themselves with minimal human intervention. By automating the detection process and using self-contained assay systems that require simple operation, the patent reduces the need for highly trained personnel while maintaining assay accuracy. The systems are designed to be user-friendly and require minimal technical expertise to operate.

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

Enables rapid, precise, and cost-effective analysis of biological samples by simplifying the detection process and reducing the need for bulk sample quantities, facilitating efficient sequencing and identification of nucleic acid sequences.

Implementation Method 1

Some bioassays are performed by tagging samples with luminescent markers that emit light of a particular wavelength. The markers are illuminated with a light source to cause luminescence, and the luminescent light is detected with a photodetector to quantify the amount of luminescent light emitted by the markers.

Methodology Applied
Scientific EffectLuminescence: Luminescence

Implementation Method 2

Jerker Widengren ET AL: 'Single-Molecule Detection and Identification of Multiple Species by Multiparameter Fluorescence Detection', Analytical Chemistry, vol. 78, no. 6, 1 March 2006, pages 2039-2050

Methodology Applied
Scientific EffectFluorescence detection: Fluorescence

Implementation Method 3

Method of determining the sequence of a nucleic acid using time resolved luminescence

Methodology Applied
Scientific EffectTime resolved luminescence: Luminescence

Data Source

PatentEP3298389B1Method of determining the sequence of a nucleic acid using time resolved luminescence
Publication Date: 2021.09.29 QUANTUM SI INC
  • EP3298389B1 patent drawingFigure 1
  • EP3298389B1 patent drawingFigure 2A~2D
  • EP3298389B1 patent drawingFigure 3~3-2

AI summary

Methods of sequencing molecules based on luminescence lifetimes and/or intensities are provided. In some aspects, methods of sequencing nucleic acids involve determining the luminescence lifetimes, and optionally luminescence intensities, of a series of luminescently labeled nucleotides incorporated during a nucleic acid sequencing reaction.