Nucleosome Measurement for Reliable Liquid Biopsy DNA Sequencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current DNA sequencing methods face challenges with inadequate DNA samples, particularly in liquid biopsies, leading to unreliable results due to low mutant allele fractions and the difficulty in detecting early-stage cancers, as traditional methods like single-gene mutation analysis and tissue biopsies are invasive and inefficient.
Innovation Solution
A method involving the measurement of nucleosomes in body fluid samples to determine the DNA level and volume required for sequencing, ensuring sufficient DNA is obtained before extraction and sequencing, using techniques such as ELISA and immunoassays to assess nucleosome levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional DNA sequencing methods are used on liquid biopsy samples, then DNA analysis can be performed, but the results are unreliable due to inadequate DNA levels and low mutant allele fractions
Solution Approach 1:
The patent applies preliminary action by measuring nucleosome levels in the body fluid sample before proceeding with DNA extraction and sequencing. This preliminary assessment allows determination of whether the sample contains sufficient DNA for reliable sequencing, preventing wasted effort on inadequate samples and enabling informed decisions about sample collection volume.
Solution Approach 2:
The patent uses nucleosomes as an intermediary marker to indirectly assess DNA levels. Instead of directly measuring DNA concentration which can be unreliable in liquid biopsies, the method measures nucleosome levels which correlate with DNA presence and provide a more reliable indicator of sample adequacy for sequencing.
2Quantity of substance
If tissue biopsy is performed to obtain DNA for sequencing, then sufficient DNA can be obtained, but the procedure is invasive and cannot be performed repeatedly
Solution Approach 1:
The patent uses nucleosomes as an intermediary marker to assess DNA availability in minimally invasive body fluid samples. This allows evaluation of liquid biopsy sample adequacy without requiring invasive tissue biopsies, enabling repeated sampling from the same patient through simple blood or plasma draws.
Solution Approach 2:
The patent replaces the mechanical invasive procedure of tissue biopsy with a biochemical measurement approach. Instead of physically removing tissue, the method uses nucleosome level measurement to assess DNA availability, substituting a minimally invasive biochemical assay for an invasive mechanical procedure.
3Measurement precision
If single-gene mutation analysis is used to detect cancer, then specific mutations can be identified, but the detection sensitivity is low for early-stage cancers
Solution Approach 1:
The patent applies preliminary action by first measuring nucleosome levels to assess the overall DNA content and quality in the sample before attempting cancer mutation detection. This preliminary assessment helps determine whether the sample has sufficient DNA for sensitive mutation analysis, particularly important for early-stage cancers where mutant allele fractions are low.
Solution Approach 2:
The patent uses nucleosomes as a proxy or copy indicator of DNA presence and quality. By measuring nucleosome levels, the method creates an indirect measure (copy) of the DNA available for cancer mutation detection, allowing assessment of sample adequacy without directly analyzing the difficult-to-detect cancer mutations themselves.
4Productivity
If DNA extraction and sequencing are performed on samples with inadequate DNA levels, then sequencing can be attempted, but the results are unreliable and resources are wasted
Solution Approach 1:
The patent applies preliminary action by measuring nucleosome levels before DNA extraction and sequencing to predict whether the sample will yield reliable results. This preliminary assessment enables filtering of inadequate samples before they enter the sequencing workflow, preventing wasted resources on sure-to-fail samples while maintaining high throughput by processing only viable samples.
Solution Approach 2:
The patent implements feedback by using nucleosome level measurements to inform subsequent decisions about sample processing. The nucleosome data provides feedback on sample adequacy, allowing the system to adjust its behavior - proceeding with sequencing only when nucleosome levels indicate sufficient DNA, thereby optimizing both productivity and reliability.
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 allows for efficient and reliable DNA sequencing by ensuring adequate DNA samples are collected, improving the detection of early-stage cancers and reducing the need for invasive biopsies.
Implementation Method 1
using techniques such as ELISA and immunoassays to assess nucleosome levels
Data Source
AI summary
The invention relates to the measurement of cell free nucleosomes for the selection of biological samples for DNA sequencing. The invention also relates to using the measurement of cell free nucleosomes to determine the volume of body fluid sample required to obtain a required level of DNA for DNA sequencing.