Inverted Microwell System for Single-Cell Analysis
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Solution Overview
Problem
Current systems for analyzing single biological particles, such as cells, often damage the particles due to electric fields used in dielectrophoresis, leading to viability issues and requiring cell lysis for analysis or product capture, which hampers high-throughput and efficient identification of therapeutically useful cells or molecules.
Innovation Solution
An inverted open microwell system that allows for rapid and efficient screening and sorting of single particles, including cells, by using dielectrophoretic forces to manipulate and position them without significant damage, enabling analysis of functional properties and recovery of viable cells, with precise delivery and manipulation of cells and reagents within the system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If dielectrophoresis is used to manipulate particles for analysis, then particle positioning and manipulation capability is improved, but particle viability and functional integrity deteriorate
Solution Approach 1:
The patent extracts the harmful electric field manipulation step from the analysis process. Instead of using dielectrophoresis to position and manipulate particles throughout the analysis, the system allows particles to flow naturally through the microfluidic channel and be analyzed in situ, removing the source of electric field-induced damage while preserving analytical capabilities
Solution Approach 2:
The patent inverts the conventional approach by not actively manipulating particles with electric fields, but rather allowing them to flow passively through the system. The analysis is performed on particles as they naturally traverse the microfluidic channel, reversing the traditional paradigm of active particle control
2Measurement precision
If particles are attached to substrate or electrode for analysis, then analysis capability is improved, but cell recovery and product capture require lysis
Solution Approach 1:
The patent introduces a microfluidic channel as an intermediary medium that allows particles to be analyzed without direct attachment to substrates or electrodes. The channel serves as a neutral environment where particles can be observed and measured while maintaining their natural state and viability, eliminating the need for attachment-based analysis
Solution Approach 2:
The system allows particles to serve themselves by flowing through the microfluidic channel under their own momentum and pressure-driven flow, without requiring attachment to external surfaces for positioning or analysis. This self-flowing mechanism preserves particle integrity throughout the analytical process
3Manufacturing precision
If prolonged electric field exposure is applied for particle manipulation, then manipulation precision is improved, but particle viability deteriorates leading to lysis and cell death
Solution Approach 1:
The patent implements a rapid flow-through approach where particles quickly traverse the microfluidic channel and complete the analysis process in minimal time. This rushing through the system prevents prolonged exposure to any potential harmful conditions and maintains particle viability throughout the process
Data Source
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AI summary
An inverted microwell (102) provides rapid and efficient microanalysis system (100) and method for screening of biological particles (128), particularly functional analysis of cells on a single cell basis. The use of an inverted open microwell system (102) permits identification of particles, cells, and biomolecules that may be combined to produce a desired functional effect also functional screening of secreted antibody therapeutic activity as well as the potential to recover cells and fluid, and optionally expand cells, such as antibody secreting cells, within the same microwell.