Platelet Nucleic Acid Screening for Sensitive Cancer Mutation Detection
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Solution Overview
Problem
Current methods for detecting clonal haematopoiesis and cancer are limited by low sensitivity due to the low abundance of tumor-derived cell-free DNA in plasma and the dilution of nucleic acids in whole blood samples, making it difficult to distinguish between malignant and non-malignant conditions.
Innovation Solution
The method involves isolating platelets from blood samples and analyzing nucleic acids, such as RNA and DNA, for the presence of clonal haematopoiesis-associated mutations and cancer-specific markers, utilizing techniques like droplet digital PCR and next-generation sequencing to enhance detection sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If cell-free DNA from plasma is analyzed for cancer detection, then the method is minimally invasive and easy to perform, but the sensitivity is low due to low abundance of tumor-derived cfDNA
Solution Approach 1:
The patent extracts and isolates platelets from whole blood samples, separating the nucleic acid-containing platelets from other blood components. This extraction concentrates the tumor-derived nucleic acids that are sequestered within platelets, thereby increasing sensitivity while maintaining the minimally invasive liquid biopsy approach
2Productivity
If whole blood samples are analyzed for nucleic acids, then the sample is readily available, but the nucleic acids are diluted making detection difficult
Solution Approach 1:
The patent extracts platelets from whole blood, isolating the nucleic acid-containing components from the diluted whole blood matrix. This extraction concentrates the target nucleic acids and removes diluting factors, thereby improving detection sensitivity while maintaining sample availability
Solution Approach 2:
The patent focuses analysis on platelets specifically, which have the unique property of sequestering tumor-derived nucleic acids. By targeting this specific cell type rather than analyzing whole blood uniformly, the method concentrates the signal where it is most abundant, improving local detection sensitivity
3Measurement precision
If platelet-derived nucleic acids are analyzed, then the sensitivity of mutation detection is significantly increased, but the method complexity increases due to platelet isolation requirements
Solution Approach 1:
The patent employs a universal platelet isolation protocol using standard centrifugation equipment and common laboratory reagents. This multi-functional approach uses widely available techniques to achieve platelet separation, reducing the need for specialized complex equipment while maintaining high detection sensitivity
Data Source
AI summary
The present invention relates to the detection of disease states such as clonal haematopoiesis and cancer by analysing thrombocytes for disease associated markers. The methods comprises steps of providing a biological sample comprising thrombocytes;extracting nucleic acid from said biological sample;analysing said nucleic acid to identify the presence of one or more clonal haematopoiesis associated mutations or cancer associated nucleic acid fragments; andindicating the presence or prognosis of clonal haematopoiesis or cancer based on the presence of one or more clonal haematopoiesis associated mutations or cancer associated nucleic acid fragments.