V-Groove Imaging Chamber for CTC Alignment
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Solution Overview
Problem
Existing methods for analyzing circulating tumor cells (CTC) in cancer patients using immunomagnetic separation face challenges with image distortion due to unbound magnetic particles, which interfere with the confirmation and analysis of captured target cells.
Innovation Solution
The use of pre-molded V-shaped grooves on the inner surface of the imaging chamber, made from transparent materials like PDMS, aligns magnetically labeled cells effectively while allowing for the removal of excess unbound magnetic particles, utilizing techniques like Buffered Hydrofluoric acid etching and Deep Reactive Ion Etching for precise structure creation, and subsequent spinning to aspirate excess ferrofluid, ensuring minimal cell loss and improved imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunomagnetic separation is used to enrich rare cells, then cell recovery is improved, but unbound magnetic particles cause image distortion and interfere with analysis
Solution Approach 1:
The patent extracts and removes unbound magnetic particles from the sample using a magnet positioned adjacent to the imaging chamber. This separation step removes the harmful unbound particles while preserving the magnetically-labeled rare cells for imaging, thereby eliminating image distortion while maintaining cell recovery
Solution Approach 2:
The patent introduces a magnet as an intermediary component between the imaging chamber and the detection system. This magnet acts as a mediator to selectively remove unbound magnetic particles without affecting the magnetically-labeled cells, resolving the contradiction between maintaining cell enrichment and eliminating imaging interference
2Manufacturing precision
If V-shaped grooves are etched on the viewing surface to align cells, then alignment precision is improved, but manufacturing complexity increases
Solution Approach 1:
The patent segments the viewing surface into distinct functional zones by etching V-shaped grooves that create alignment channels. These grooves divide the surface into structured pathways that guide cell positioning, achieving precise alignment while maintaining a relatively simple overall device structure
Solution Approach 2:
The patent replaces complex mechanical alignment mechanisms with statically etched V-shaped grooves on the viewing surface. This substitution eliminates the need for moving parts or complex adjustment mechanisms, achieving precise cell alignment through simple surface topography that can be manufactured using standard etching techniques
3Productivity
If excess ferrofluid is used in immunomagnetic separation, then cell capture efficiency is improved, but image quality deteriorates due to particle interference
Solution Approach 1:
The patent extracts excess unbound ferrofluid particles from the sample using an external magnet positioned near the imaging chamber. This removal step eliminates the harmful excess particles that cause image degradation while preserving the magnetically-labeled cells, thereby maintaining high capture efficiency without compromising image quality
Solution Approach 2:
The patent changes the concentration parameter of ferrofluid in the sample by removing excess unbound particles through magnetic separation. This parameter adjustment optimizes the balance between having sufficient ferrofluid for effective cell capture and maintaining low enough concentration to avoid image interference during analysis
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 approach enables 95-99% recovery of CTCs and reduces excess ferrofluid concentration to less than 2 ug/ml, significantly improving image quality and allowing for optimal quantitative measurements and morphological data collection.
Implementation Method 1
magnetic-responsive particles having a binding agent for producing magnetically-labeled species
Implementation Method 2
susceptible to immunospecific or non-specific binding with magnetic-responsive particles
Implementation Method 3
an external magnetic gradient is employed to attract magnetically labeled target specimens present in a collection chamber to one of its surfaces
Implementation Method 4
The movement of magnetically labeled biological specimens to the collection surface is obtained by applying a vertical magnetic gradient
Implementation Method 5
Once the magnetically labeled biological specimens are pulled sufficiently close to the surface by the externally applied gradient, they come under the influence of an intense local gradient produced by the ferromagnetic collection structure and are immobilized
Implementation Method 6
The collection surface is provided with a ferromagnetic capture structure, such as plurality of ferromagnetic lines
Implementation Method 7
These magnetically labeled rare cells are subjected to Time Delay Integration Imaging (TDI) in the CellTracks Platform
Implementation Method 8
subsequent spinning to aspirate excess ferrofluid
Data Source
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AI summary
A method for removing excess unbound ferrofluid and imaging immunomagnetically enriched circulating tumor cells is provided. A vessels having a preformed grooves in the viewing surface is optimally designed for cell alignment and imaging. After separating the unbound particles by centrifugation, an externally-applied force is applied to transport magnetically responsive particle-CTC complex toward the transparent collection wall. The grooved inner surface of the viewing face of the chamber provide uniform distribution of the particles for easy imaging. The invention is also useful in conducting quantitative analysis and sample preparation in conjunction with automated cell enumeration techniques as in quantitative analysis of CTC in disease.