Microfluidic Chamber for Single-Cell Antibody Binding Analysis
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Solution Overview
Problem
Conventional methods for producing monoclonal antibodies are inefficient due to low fusion rates of antibody-secreting cells with murine myeloma cells, requiring large numbers of animals and lengthy clonal expansion processes, which are time-consuming and costly.
Innovation Solution
A microfluidic method involving a chamber with a reversible trap allows for the retention and analysis of single antibody-producing cells, enabling direct measurement of antigen-antibody binding kinetics using techniques like fluorescence imaging, SPR spectroscopy, and interferometry, without the need for extensive clonal expansion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional hybridoma technology is used to produce monoclonal antibodies, then antibody production is achieved, but the process is time-consuming and expensive due to low fusion efficiency
Solution Approach 1:
The invention extracts and isolates individual antibody-secreting cells from the complex mixture of cells in the immune response. By capturing single cells in microfluidic chambers, the method eliminates the need for clonal expansion and allows direct measurement of antibody binding kinetics from the original single cells, thereby reducing time loss while maintaining productivity
Solution Approach 2:
The invention segments the complex immune response into individual cell-level analyses. By using microfluidic devices to isolate and analyze single antibody-secreting cells, the method divides the population-level process into discrete unit operations, enabling direct measurement without requiring expansion to measurable concentrations
2Quantity of substance
If hybridoma technology is used to amplify antibody quantities, then sufficient antibody concentration is achieved for binding affinity measurements, but the process requires fusions from hundreds to thousands of animals
Solution Approach 1:
The invention extracts individual antibody-secreting cells directly from the immune response without requiring animal fusion procedures. By capturing single cells in microfluidic chambers, the method obtains sufficient antibody material from the original single cells to perform binding affinity measurements, eliminating the need to use hundreds to thousands of animals
Solution Approach 2:
The invention creates a functional copy of the antibody binding assay using single cells in microfluidic chambers. Instead of requiring physical expansion of the cell population, the method uses the microfluidic system to replicate and measure the binding kinetics of individual cells, achieving the necessary data without additional animal use
3Quantity of substance
If clonal expansion is performed to produce monoclonal antibodies, then sufficient antibody quantity is achieved, but the process is costly and time-consuming
Solution Approach 1:
The invention extracts and analyzes antibody binding kinetics directly from single antibody-secreting cells without performing clonal expansion. By capturing individual cells in microfluidic chambers and measuring their antibody production and binding activity, the method obtains sufficient data without the time-consuming expansion process
Solution Approach 2:
The invention performs preliminary measurement of binding kinetics directly from single cells before any clonal expansion would occur. By capturing and analyzing individual cells in their original state, the method obtains the necessary binding affinity data upfront, eliminating the need for subsequent expansion and associated time loss
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 method allows for the efficient measurement of antigen-antibody binding kinetics, reducing the need for large-scale animal immunization and clonal expansion, thereby streamlining the production and selection of monoclonal antibodies.
Implementation Method 1
exposing the protein produced by the cell to a capture substrate, wherein the capture substrate is in fluid communication with the protein produced by the cell and wherein the capture substrate is operable to bind the protein produced by the cell
Implementation Method 2
retaining the cell within a chamber having an inlet and an outlet
Implementation Method 3
flowing a first fluid volume comprising the biomolecule through the inlet into the chamber and out the outlet
Data Source
AI summary
There are provided methods, and devices for assaying for a binding interaction between a protein, such as a monoclonal antibody, produced by a cell, and a biomolecule. The method may include retaining the cell within a chamber having an aperture; exposing the protein produced by the cell to a capture substrate, wherein the capture substrate is in fluid communication with the protein produced by the cell and wherein the capture substrate is operable to bind the protein produced by the cell; flowing a fluid volume comprising the biomolecule through the chamber via said aperture, wherein the fluid volume is in fluid communication with the capture substrate; and determining a binding interaction between the protein produced by the cell and the biomolecule.