Mesofluidic Device for Simultaneous Rare Cell Sorting
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Solution Overview
Problem
Current methods for detecting and characterizing rare cells in biological samples, such as cancer cells, are limited by their inability to selectively and simultaneously identify multiple heterogeneous sub-populations, require large blood volumes, and are not compatible with frozen samples or immunofluorescence and FISH characterization, leading to low detection capacity and restricted use.
Innovation Solution
A mesofluidic device with laminar-flow fluidic chambers functionalized with specific antibodies allows for the selective, specific, and simultaneous sorting of rare target cells, enabling positive and negative selection of cell populations in a single step, compatible with IF and FISH characterization, and capable of using small blood volumes, including frozen samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If single-step detection methods using unique antibodies (e.g., anti-EpCAM) are used, then detection simplicity is improved, but detection capacity is limited to single cell populations
Solution Approach 1:
The device segments the detection process into multiple independent fluidic chambers, each functionalized with different antibodies targeting specific cell populations. This allows simultaneous detection of multiple heterogeneous cell types (CTC, CSC, CEC, mesenchymal cells) while maintaining the simplicity of single-antibody binding mechanisms in each chamber.
Solution Approach 2:
The mesofluidic device serves multiple functions: it can detect various cell types (tumor cells, stem cells, endothelial cells), work with different sample types (fresh and frozen blood), and enable multiple characterization methods (immunofluorescence and FISH) within a single platform, replacing multiple separate detection systems.
2Adaptability or versatility
If two-step methods involving magnetic beads are used, then detection capacity for multiple cell types is improved, but device complexity increases
Solution Approach 1:
The invention extracts and eliminates the complex magnetic bead manipulation steps from the detection process. Instead of requiring magnetic separation and multiple washing steps, cells are directly captured on antibody-functionalized surfaces in fluidic chambers, simplifying the procedure to a single incubation and detection step while maintaining multi-cell-type detection capacity.
Solution Approach 2:
The antibody-functionalized solid surface acts as an intermediary that directly captures cells of interest from the biological sample. This eliminates the need for magnetic beads as intermediaries, reducing procedural complexity while maintaining the ability to selectively capture multiple cell populations through different antibodies.
3Measurement precision
If large blood volumes (5-10 ml) are required for detection, then detection sensitivity is improved, but sample volume requirement becomes restrictive
Solution Approach 1:
The device creates localized high-concentration antibody environments on the functionalized surfaces within each fluidic chamber. This local concentration of detection reagents enhances binding efficiency and detection sensitivity, allowing effective detection with smaller blood volumes (less than 5 ml) compared to methods requiring bulk processing of large volumes.
4Reliability
If methods are not compatible with frozen samples, then detection reliability for fresh samples is maintained, but sample type versatility is reduced
Solution Approach 1:
The device allows preliminary freezing of blood samples without affecting subsequent detection. The antibody-functionalized chambers can directly process thawed frozen samples, and the detection protocol accounts for the frozen state, maintaining reliable detection across both fresh and frozen sample types, thereby expanding clinical utility.
5Measurement precision
If single population detection is used, then selectivity for specific markers is improved, but ability to characterize heterogeneous cell populations is reduced
Solution Approach 1:
The detection system is segmented into multiple independent fluidic chambers, each functionalized with antibodies against specific markers (EpCAM for CTC, CD133 for CSC, CD146 for CEC, etc.). This segmentation allows each chamber to maintain high selectivity for its target population while the overall device characterizes heterogeneous cell populations through the combined results from all chambers.
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
The device achieves efficient detection and characterization of rare cell sub-populations, including those not expressing EpCAM, with enhanced sensitivity and versatility, suitable for various medical applications, including cancer diagnosis and personalized medicine.
Implementation Method 1
laminar-flow fluidic chambers each comprising a surface functionalized with molecules, at least some of which are able to form a bond with a receptor molecule borne by the target cells
Implementation Method 2
at least one pump adapted to cause a sample of the biological solution to circulate in the fluidic chambers of the first row then of the last row
Implementation Method 3
a first row of at least two laminar-flow fluidic chambers
Data Source
AI summary
A device for sorting of rare target cells in a biological sample comprises a first row of at least two laminar-flow fluidic chambers, each comprising an inlet connected to a reservoir of a biological solution and an outlet and a last row of laminar-flow fluidic chambers equal in number to the number of chambers of the first row. Each last row fluidic chamber comprises an inlet connected to an outlet of a chamber of the first row and an outlet. A reservoir for collecting solution is connected to each outlet of the fluidic chambers of the second row, at least one pump causing a sample of the solution to circulate in the fluidic chambers of the first row then of the last row, wherein the fluidic chambers include a surface functionalized with molecules, at least some of which able to bond with a receptor molecule borne by the target cells.