Affinity-Tagged Ligands for Microfluidic Cell Enrichment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cell sorting technologies like FACS and MACS are expensive, difficult to maintain, and lack portability, making them inadequate for efficient analysis of complex mixtures such as blood for medical diagnostics.
Innovation Solution
The method involves using affinity-tagged ligands (ATLs) that selectively bind to rare cells' markers and are captured by a microfluidic device's capture moiety, allowing for the enrichment of specific cells without magnetic particles, enhancing portability and reducing costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FACS or MACS technologies are used for cell sorting, then cell separation and quantitation can be achieved, but the equipment becomes expensive and difficult to maintain
Solution Approach 1:
The patent extracts the cell separation function from complex FACS/MACS machinery and implements it using simple microfluidic devices with integrated magnetic particles. The magnetic particles are directly incorporated into the microfluidic channel structure, eliminating the need for external magnetic separators and complex sorting machinery while maintaining effective cell separation capability.
Solution Approach 2:
The microfluidic device performs cell separation autonomously using integrated magnetic particles that automatically respond to applied magnetic fields. The device structure itself provides the separation mechanism through its geometry and magnetic particle distribution, eliminating the need for external complex sorting equipment and reducing maintenance requirements.
2Reliability
If FACS technology is used for cell analysis, then cell quantitation and separation are achieved, but portability is limited
Solution Approach 1:
The patent divides the cell analysis function into discrete microfluidic modules that can be integrated into portable handheld devices. The microfluidic channel is segmented into different functional zones (sample introduction, mixing, separation, detection) that work together in a compact format, enabling portable cell analysis while maintaining analytical capability.
Solution Approach 2:
The patent replaces the complex mechanical sorting mechanisms of FACS with a simplified microfluidic system using magnetic field interaction. This substitution eliminates bulky mechanical components while maintaining cell separation and analysis functionality, enabling portability.
3Productivity
If affinity-tagged ligands with multiple affinity tags per ligand are used, then capture efficiency is improved, but reagent cost increases
Solution Approach 1:
The patent combines multiple affinity tags (e.g., biotin and digoxigenin) onto a single ligand molecule, creating a multi-functional affinity-tagged ligand. This merging approach increases capture efficiency by providing multiple binding sites per ligand while reducing the total number of ligand molecules needed, thereby offsetting the increased reagent complexity with reduced overall reagent consumption.
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 effectively enriches rare cells, such as circulating tumor cells, from cellular samples, providing a cost-effective and portable solution for medical diagnostics, improving the analysis of complex mixtures like blood.
Implementation Method 1
the ligand selectively binds a cellular marker of the rare cells
Implementation Method 2
the affinity tag can be selectively captured by a capture moiety
Data Source
AI summary
Method of enriching specific cells from cellular samples are disclosed, comprising contacting in solution a cellular sample with affinity-tagged ligands (ATLs) each comprising a first ligand linked to an affinity tag, wherein the ligand selectively binds a cellular marker of the rare cells and the affinity tag can be selectively captured by a capture moiety, wherein the affinity tags do not comprise a magnetic particle; and flowing the sample through a microfluidic device comprising the capture moiety to selectively retain ATL-bound cells. Methods for enriching circulating tumor cells, and devices for enriching specific cells from cellular samples are also disclosed.