Structured Capture Array for Biomarker Isolation
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Solution Overview
Problem
Current methods for diagnosing and monitoring cancer, such as solid biopsies, are invasive, limited in scope, and do not accurately reflect the genetic heterogeneity of tumors, while liquid biopsies offer a less invasive alternative but require optimized protocols for efficient extraction of biomarkers from blood.
Innovation Solution
A method involving a structured capture array with topographical features and controlled humidity to isolate molecules and molecular complexes from complex fluids, utilizing surface tension and capillary forces to trap and separate low molecular weight markers like DNA, RNA, and exosomes, allowing for efficient isolation without pre-treatment of the fluid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If solid biopsy is used for cancer diagnosis, then tumor tissue can be obtained for analysis, but the procedure is highly invasive and limited to visible tumors
Solution Approach 1:
The invention extracts and isolates circulating tumor cells (CTCs) from liquid biopsy samples (blood, plasma, serum) instead of requiring solid tissue biopsy. This extraction approach allows obtaining tumor-derived material through minimally invasive blood draws, directly resolving the contradiction between obtaining sufficient tumor material and reducing invasiveness
Solution Approach 2:
The invention uses circulating tumor cells (CTCs) as an intermediary medium that carries tumor genetic information from the primary tumor to the bloodstream. By analyzing these intermediary CTCs in liquid biopsy, the system obtains tumor tissue information without directly accessing or removing solid tumor tissue, thus eliminating the need for invasive biopsies while still achieving comprehensive tumor analysis
2Loss of time
If solid biopsy is performed once from one tumor portion, then a sample is obtained, but the results do not reflect the full genetic heterogeneity of the tumor
Solution Approach 1:
The invention creates a universal liquid biopsy platform that can repeatedly sample circulating tumor cells from the bloodstream. This multi-functional approach allows frequent sampling over time and from different anatomical regions, comprehensively capturing tumor genetic heterogeneity that would be missed by single-point solid biopsies
Solution Approach 2:
The invention performs preliminary isolation and enrichment of circulating tumor cells from blood samples before genetic analysis. This preliminary action on liquid samples enables repeated sampling and comprehensive mapping of tumor heterogeneity across different time points and treatment responses, providing a complete picture of evolutionary changes that solid biopsies cannot capture
3Quantity of substance
If traditional centrifugation protocols are used to extract DNA from blood plasma, then DNA can be obtained, but the protocol is highly restrictive requiring EDTA tubes, cooling, and handling within 2 hours
Solution Approach 1:
The invention employs self-service microfluidic structures with integrated magnetic particles that automatically isolate circulating tumor cells and extract nucleic acids directly from whole blood or plasma samples. This self-service system eliminates the need for complex pre-processing steps, EDTA tubes, cooling requirements, and strict timing constraints, allowing sample processing under simpler, more flexible conditions while maintaining high DNA extraction efficiency
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 efficient, one-step isolation of low molecular weight biomarkers from raw biological fluids, overcoming the limitations of traditional biopsy methods by providing a repeatable and less invasive means for cancer diagnosis and monitoring.
Implementation Method 1
utilizing surface tension and capillary forces to trap and separate low molecular weight markers like DNA, RNA, and exosomes
Implementation Method 2
utilizing surface tension and capillary forces to trap and separate low molecular weight markers like DNA, RNA, and exosomes
Data Source
AI summary
A method for isolating molecules and/or molecular complexes having a radius of gyration smaller or equal to 2 μm from a complex fluid, including the steps of: a) contacting a complex fluid with a structured capture array having topographical features, wherein the structured capture array is placed in an environment with surrounding humid air humidity of at least 40% based on the maximal moisture content, b) covering the deposited complex fluid with a covering element, wherein the surface tension of the complex fluid between the covering element and the structured capture array defines at least a front and a rear meniscus; and c) dragging either the covering element or the structured capture array in one direction at a speed of at most 2 mm·s−1 for displacing the complex fluid, resulting in that the molecules and/or the molecular complexes are trapped inside the cavities.