High Throughput Immune Cell Engager Screening Assay
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Solution Overview
Problem
Current assays for evaluating immune cell engagers are limited in their ability to simultaneously analyze multiple parameters related to immune and tumor cell interactions, such as cell death, apoptosis, and cytokine changes, often requiring diverse labeling and analysis methods and lacking high-throughput capabilities.
Innovation Solution
A method and system for high-throughput assays that co-culture immune cells with tumor cells in the presence of potential immune cell engagers, allowing for simultaneous kinetic analysis of cell death, apoptosis, ATP concentration, and cytokine changes using multi-well plates and automated imaging, enabling the assessment of multiple parameters from small volumes of samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple parameters are analyzed using diverse labeling and analysis methods, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent combines multiple analysis methods (cell death detection, apoptosis measurement, cytokine analysis) into a single integrated assay system using multi-well plates with automated imaging, eliminating the need for separate diverse labeling methods while maintaining measurement precision across all parameters
Solution Approach 2:
The assay system is designed with universal multi-functionality to simultaneously perform multiple analyses (nuclear stain loss, caspase labeling, ATP measurement, cytokine detection) using a single platform, reducing device complexity while preserving the ability to measure multiple parameters with high precision
2Productivity
If multiple parameters are analyzed simultaneously, then productivity is improved, but measurement precision deteriorates
Solution Approach 1:
The patent segments the assay into distinct modular components (different fluorescent labels, separate detection channels, independent analysis methods) that can be simultaneously measured without interference, enabling high-throughput multi-parameter analysis while maintaining the precision of individual measurements through automated imaging and analysis
3Loss of substance
If small volumes of materials are used, then loss of substance is reduced, but measurement precision worsens
Solution Approach 1:
The patent employs fluorescent labels and luminescent signals that provide high-contrast optical changes detectable by automated imaging systems, enabling precise measurement of parameters even in small sample volumes by amplifying the detectable signal through fluorescence and luminescence rather than relying on large material quantities
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
Enables the efficient analysis of multiple parameters associated with immune and tumor cell interactions, allowing for the evaluation of hundreds of samples in parallel, providing detailed kinetic data on cell death, apoptosis, and cytokine changes, thereby facilitating the assessment of immune cell engager molecules.
Implementation Method 1
target cells, such as tumor or primary cells, are stained with a dye, for example where cells are stably transfected with a nuclear fluorescence protein
Implementation Method 2
loss of ATP activity measured in luminescence assays
Implementation Method 3
apoptosis may be measured by the use of stains whose signal depends on presence of apoptosis factors such as caspases
Data Source
AI summary
The present disclosure provides methods and systems for high throughput assays for testing immune cell engager molecules and potential immune cell engager molecules. In some embodiments, multiple parameters, for example, in connection with engagement of tumor cells by immune cells such as T cells and in connection with tumor cell death, may be analyzed from the same samples in the assays, and, in some cases, may be analyzed simultaneously. In some embodiments, the methods and systems allow for determining the kinetics of various parameters.