CTC Filtration Membrane with Impedance-Based Real-Time Detection
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Solution Overview
Problem
Existing methods for isolating and detecting circulating tumor cells (CTCs) in blood are limited by low sensitivity, require small blood samples, fail to detect CTCs that have lost the EpCAM protein, and lack real-time, direct detection capabilities, especially at early cancer stages.
Innovation Solution
A system using electrodes to generate an alternating electrical signal for dielectrophoretic capture and release of CTCs based on impedance variations, allowing real-time detection and discrimination of cell types without immunolabeling, using a filter membrane with specific pore dimensions and materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If immunolabeling techniques are used to capture CTCs, then CTCs can be detected based on EpCAM protein, but the method fails to detect CTCs that have lost the EpCAM protein during epithelial-mesenchymal transition
Solution Approach 1:
The invention changes the detection parameter from EpCAM protein-specific immunolabeling to physical properties (size, deformability) that are invariant across different CTC states. This allows detection of both EpCAM-positive and EpCAM-negative CTCs by measuring mechanical properties rather than molecular markers.
Solution Approach 2:
The device creates a universal detection platform that can identify all CTCs regardless of their molecular phenotype. By using physical property measurement instead of protein-specific binding, the system achieves multi-functionality in detecting differentiated and undifferentiated CTCs alike.
2Ease of operation
If small blood samples (7.5 ml) are used for CTC isolation, then the isolation process is manageable, but the number of CTCs detected is very low due to their low concentration
Solution Approach 1:
The invention changes the detection approach from relying on large sample volumes to using highly sensitive physical property measurement. This allows effective detection in small samples by improving the sensitivity of the measurement technique rather than increasing the sample quantity.
Solution Approach 2:
The invention replaces traditional mechanical separation methods requiring large volumes with an electrical measurement system that can detect rare cells in small samples through impedance variations, substituting mechanical processing with electrical detection.
3Quantity of substance
If in vitro isolation methods are used, then CTCs can be captured, but real-time detection and counting capabilities are lacking
Solution Approach 1:
The invention merges the capture and detection functions into a single integrated process. CTCs are captured and counted simultaneously through impedance measurement as they pass through the device, eliminating the time delay between capture and detection that characterizes separate in vitro methods.
Solution Approach 2:
The device enables continuous real-time detection as CTCs flow through the system, maintaining constant monitoring rather than requiring discrete sampling and analysis steps. This provides uninterrupted detection capability throughout the measurement period.
4Measurement precision
If immunolabeling is performed on captured cells, then tumor cell identification is possible, but cell integrity is altered before biological analyses or culturing
Solution Approach 1:
The invention replaces chemical immunolabeling with physical impedance measurement to identify tumor cells. This substitution preserves cell integrity by avoiding chemical modifications while still achieving accurate tumor cell identification through detection of size and electrical property variations.
Solution Approach 2:
The device allows cells to maintain their natural state without external chemical modification. Cells passively provide their intrinsic electrical and mechanical properties for detection, eliminating the need for exogenous labels that would compromise their suitability for downstream biological analyses.
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 real-time, direct detection and isolation of CTCs with high sensitivity, preserving cell integrity and viability, and providing immediate medical information for personalized patient care, without the need for sample preparation or transportation.
Implementation Method 1
A system using electrodes to generate an alternating electrical signal for dielectrophoretic capture and release of CTCs based on impedance variations
Implementation Method 2
using a filter membrane with specific pore dimensions and materials
Data Source
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AI summary
The invention relates to a system for detecting at least one species present in a fluid, preferably for detecting at least one circulating cell or aggregate of cells present in a human or animal biological fluid, and in particular circulating tumour cells (CTC) present in a blood fluid, the detection system comprising means (20) for filtering the fluid, the filtering means (20) comprising a filtering membrane (21), the filtrating membrane comprising at least one pore (22) designed to retain a species of a given type present in the fluid, the filtration means (20) further comprising at least one opening (23) designed to ensure, during operation within the fluid, the continuous circulation of the biological fluid, even when the at least one pore (22) is occupied.