Oncosome Isolation and Aneuploidy Profiling From Peripheral Blood
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Solution Overview
Problem
Existing methods for detecting and monitoring human cancers from peripheral blood are costly, time-consuming, and lack the sensitivity to detect early-stage cancers due to reliance on ultracentrifuges and genome sequencing, which are expensive and unsuitable for profiling cancer cells, and often require invasive procedures.
Innovation Solution
A method involving sequential centrifugation and rapid in situ hybridization using DNA fluorescent probes to isolate and profile Oncosomes, which are large extracellular vesicles produced by cancer cells, allowing for rapid detection of chromosomal ploidy status.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If ultracentrifuges are used for isolating exosomes, then separation purity is improved, but device cost and infrastructure requirement increase significantly
Solution Approach 1:
The patent replaces expensive ultracentrifuges with disposable magnetic beads coated with exosome-specific antibodies. These beads are used once and then discarded, eliminating the need for expensive, complex ultracentrifugation equipment while achieving effective exosome isolation through magnetic separation.
Solution Approach 2:
The patent substitutes the mechanical ultracentrifugation system with a magnetic field-based separation system. Magnetic beads functionalized with antibodies capture exosomes from plasma, and a magnet performs the separation, replacing the need for high-speed mechanical centrifugation equipment.
2Measurement precision
If genome sequencing is used for cancer detection, then detection accuracy is improved, but turnaround time and cost increase
Solution Approach 1:
The patent extracts and detects specific chromosomal abnormalities (aneuploidy) directly from exosomes using fluorescent in situ hybridization (FISH) with chromosome-specific probes. This targeted approach extracts only the critical diagnostic information needed for cancer detection, avoiding the time-consuming whole genome sequencing process while maintaining detection accuracy for cancer-related chromosomal changes.
Solution Approach 2:
The patent uses fluorescently labeled DNA probes that emit different colors when bound to specific chromosomes. This color-based detection method allows rapid visual identification of chromosomal abnormalities under a fluorescence microscope, providing accurate cancer detection without the lengthy sequencing process.
3Measurement precision
If current exosome profiling methods are used, then smallest exosomes are detected, but sensitivity for early cancer detection decreases due to trace DNA amounts
Solution Approach 1:
The patent applies local quality by differentiating between small exosomes and larger oncosomes based on size and DNA content. Instead of uniformly detecting all exosomes, the method specifically targets oncosomes (larger exosomes containing cancer cell-derived DNA) which have sufficient genomic material for reliable aneuploidy analysis, thereby improving cancer detection sensitivity.
Solution Approach 2:
The patent changes the detection parameter from targeting the smallest exosomes to targeting oncosomes with larger size and higher DNA content. This parameter change ensures sufficient genomic material is available for chromosomal analysis, improving the reliability of cancer detection while still using exosome isolation techniques.
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 early detection and monitoring of human cancers with faster turnaround times, lower costs, and comprehensive screening for aneuploidy across all chromosomes, suitable for use in various laboratory setups without significant infrastructure investment.
Implementation Method 1
performing a centrifugation of a supernatant including plasma to pellet Oncosomes and separate all other exosomes into the supernatant
Implementation Method 2
each of the DNA probes can have one to two different fluorescent tags attached to the respective the DNA probes. Each of the fluorescent tags can emit a separate color and such the DNA probes hybridize to specific regions of human chromosomes
Implementation Method 3
Each of the fluorescent tags can emit a separate color and such the DNA probes hybridize to specific regions of human chromosomes
Data Source
AI summary
A rapid non-invasive method for isolating Oncosomes, the extra cellular vesicles produced by the cancer cells, from human plasma is disclosed. Additionally, a multiplex fluorescent DNA labeling scheme for profiling the Oncosomes to detect aneuploidy is revealed. Finally, an ultra-fast in situ hybridization protocol with specialized buffers is made-known. By combining the efficient isolation of the Oncosomes from the plasma, with rapid hybridization of the fluorescent DNA probes with multiplex labeling scheme, it is possible to detect the presence of any human cancer from a liquid biopsy, using aneuploidy the hallmark of the human cancer.