Microwell Array Platform for Single Cell Identity Tracking
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Solution Overview
Problem
Current single cell assays are limited in tracking the responses of individual cells in multiple processes and lack the ability to identify and track the same cells over time, hindering their effectiveness in studying immune cell responses and tumor interactions, especially in cancer immunotherapy where tumor heterogeneity and patient variability pose challenges.
Innovation Solution
A high-throughput microwell array platform that allows for real-time monitoring of T cell cytotoxicity and cytokine secretion, combined with a mathematical model to quantify immune-cancer cell interactions, enabling the identification and tracking of individual cells and their responses to stimuli, and the evaluation of T cell cytotoxicity and cytokine secretion at a single cell level.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single cell assays are used to study individual cell responses, then measurement precision is improved, but the ability to track the same cells across multiple processes is lost
Solution Approach 1:
The assay system segments the cell population into individually addressable units by distributing cells into separate microwells in a grid pattern. Each microwell contains a specific cell that can be individually monitored, allowing both precise single-cell measurement and tracking of the same cell across multiple assays through its spatial position in the grid.
Solution Approach 2:
The system creates a spatial map copy of cell positions in the microwell grid that can be referenced across multiple assays. This positional information serves as a persistent identifier that allows tracking of the same cell through different chemical and physical processes without requiring complex cell tagging or identification systems.
2Productivity
If high-throughput screening is implemented to increase productivity, then the number of cells tested increases, but the ability to perform multiple processes on the same cells is reduced
Solution Approach 1:
The microwell grid system serves multiple functions: it enables high-throughput screening of many cells simultaneously while also allowing the same cells to undergo multiple different assays. The standardized grid format is compatible with various chemical treatments, physical processes, and detection methods, making the system universally applicable across different experimental conditions.
Solution Approach 2:
The system adds the spatial dimension of microwell position as an additional identifier beyond cell type or population. This dimensional approach allows millions of individual cell assays to be performed while maintaining the ability to track specific cells across different assays by referencing their two-dimensional grid coordinates, thereby resolving the conflict between throughput and tracking capability.
3Measurement precision
If current single cell analysis methods are used, then one single aspect of immune cell response can be studied, but comprehensive investigation of overall immune cell function is limited
Solution Approach 1:
The system merges multiple assay capabilities into a single integrated platform. By combining the microwell grid system with compatible detection methods, researchers can simultaneously or sequentially perform multiple different assays on the same cells, including cytokine secretion detection, cytotoxicity assessment, and other immune cell functional evaluations, thereby achieving comprehensive investigation of immune cell function.
Data Source
AI summary
Disclosed is a technology for assaying individual cells, in which the identity of each individual cell in an ordered array is determined from coordinates assigned to it, and can be readout at high throughput with microscope. The method is able to test responses of millions of identical cells in multiple chemical and physical processes with superior statistics power to facilitate deep data mining.