Laser-Assisted CTC Isolation via Polymeric Adhesive Blister
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Solution Overview
Problem
Current methods for isolating circulating tumor cells (CTCs) from peripheral blood face challenges due to low concentration, invasiveness, and the need for precise detection and manipulation, especially during the Epithelial-to-Mesenchymal Transition (EMT) phase, where existing technologies compromise cellular viability and purity.
Innovation Solution
A simplified laser-assisted transfer method using a semi-transparent polymeric adhesive tape as a donor substrate, which absorbs laser radiation, allowing for the selective movement and isolation of CTCs and DTCs without fluorescent dyes, enabling 'laser negative selection' for non-invasive, high-purity cell isolation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional biopsy methods are used to obtain tumor tissue, then sufficient tissue samples can be obtained for analysis, but patient discomfort increases and procedure invasiveness worsens
Solution Approach 1:
The patent uses circulating tumor cells (CTCs) as an intermediary medium between the primary tumor and the analysis target. Instead of directly accessing tumor tissue, CTCs that naturally circulate in the bloodstream are captured and analyzed, providing indirect but sufficient information about tumor characteristics without requiring invasive tissue biopsy procedures
Solution Approach 2:
The patent creates a liquid copy of tumor information through CTCs. These circulating cells serve as a representative sample or copy of the primary tumor's genetic and molecular characteristics, allowing researchers to study tumor properties through blood samples rather than directly from the tumor tissue itself
2Object-affected harmful factors
If liquid biopsy is used to extract CTCs from peripheral blood, then invasiveness is reduced and accessibility is improved, but CTC concentration becomes very low making isolation difficult
Solution Approach 1:
The patent applies local quality by using specific surface markers (such as EpCAM for epithelial cells or CD45 for hematopoietic cells) that are locally expressed on CTC surfaces. This allows the isolation system to selectively identify and capture CTCs based on their unique local molecular characteristics, distinguishing them from the vast number of other blood cells despite low concentration
Solution Approach 2:
The patent changes the isolation parameter from general physical properties to specific surface antigen expression levels. By detecting and responding to the presence of specific markers on CTC surfaces, the system can selectively isolate these rare cells from blood samples without requiring high CTC concentration, using immunomagnetic or fluorescence-activated cell sorting techniques
3Quantity of substance
If immunomagnetic separation is used to isolate CTCs, then CTC concentration and purity can be increased, but cellular viability may be compromised
Solution Approach 1:
The patent replaces harsh mechanical and chemical isolation methods with gentler magnetic field-based immunomagnetic separation. This substitution allows CTCs to be captured through specific antibody-antigen binding followed by magnetic separation, avoiding the mechanical stress and chemical exposure that would otherwise compromise cell viability while still achieving high concentration and purity
4Measurement precision
If fluorescent staining is used to identify tumor cells, then detection precision is improved, but cellular integrity and natural state are compromised
Solution Approach 1:
The patent extracts the detection function from the cell itself by using fluorescently labeled antibodies that bind to specific surface markers on CTCs. This allows the detection precision to be improved through fluorescent signal detection while the cell's natural state and integrity remain preserved, as the staining targets external surface proteins rather than requiring internal cell modification or disruption
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 method enhances the purity and viability of CTCs, allowing for precise isolation and manipulation of single cells or clusters, overcoming the limitations of UV damage and environmental disruption in existing technologies, and is particularly effective for low-concentration CTCs.
Implementation Method 1
A fluorescent staining of at least one of the cell populations (tumor and non-tumor cells) present in the liquid specimen is required to identify by means of optical and fluorescence microscopy the location of the cells to be isolated by a simplified laser-assisted transfer process. The semi-transparent polymeric adhesive tape is partially transparent to visible light and absorbent to the laser wavelength.
Data Source
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AI summary
The present invention relates to a method and system for detecting, manipulating and isolating circulating tumor cells found in organic fluids by a simplified laser-assisted transfer process. A liquid specimen of the organic fluid containing an enriched population of tumor cells and a population of non-tumor cells is spread onto a donor substrate with an interlayer comprising a semi-transparent polymeric adhesive tape. A fluorescent staining of at least one of the cell populations present in the liquid specimen is required to identify by means optical and fluorescence microscopy the location of the cells to be manipulated and/or isolated. The laser beam energy is absorbed by the polymeric adhesive tape giving place to the formation of a blister that mechanically interacts with the liquid specimen and such interaction can induce the expulsion of a portion of the liquid specimen comprising the selected tumor cells or non-tumor cells, which can be a single cell or a cell cluster, towards the receiving substrate.