Printed Microarray for High-Throughput Antibody Screening
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Solution Overview
Problem
Current screening assays for identifying compounds or molecules involved in disease processes are time-consuming and often fail to recover the screened compounds, lacking efficiency and effectiveness.
Innovation Solution
A printed microarray of cell-derived products is used, where each position corresponds to a secretion from a single cell, with a conformable support allowing for rapid screening of secreted products like antibodies or cytokines, and a moldable slab with microwells enables high-throughput analysis and detection of associations between secreted products and target ligands.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional screening assays are used to identify compounds or molecules, then the screening process can be performed, but the time required is excessive and the compounds cannot be recovered
Solution Approach 1:
The invention segments the screening process by separating the compound library into individual wells of a microarray format, allowing parallel processing of thousands of compounds simultaneously. Each well contains a single compound or small pool, enabling high-throughput screening while maintaining the ability to recover specific compounds by identifying positive well locations.
Solution Approach 2:
The invention creates physical copies of the compound library arranged in a microarray format on a solid support. This copying allows the screening assay to be performed in parallel across numerous copies simultaneously, dramatically increasing throughput while preserving the original compound identities for recovery through location-based identification.
2Productivity
If conventional screening assays are used, then compounds can be screened, but the compounds cannot be recovered post-screening
Solution Approach 1:
The invention introduces a solid support (microarray substrate) as an intermediary between the compound library and the screening assay. This intermediary maintains the spatial organization of compounds throughout the screening process, allowing positive hits to be identified by their location on the substrate and enabling subsequent recovery of the original compounds from those specific locations.
Solution Approach 2:
The invention employs detectable signals (such as color changes, fluorescence, or other optical signals) to indicate positive screening results at specific well locations. These signal changes allow rapid identification of active compounds without disrupting the compound positions, facilitating both high-throughput screening and subsequent compound recovery from identified locations.
3Loss of time
If a printed microarray with single-cell deposits is used, then screening time is reduced and efficiency is enhanced, but the device complexity increases
Solution Approach 1:
The invention uses a universal microarray platform that can screen multiple different compound libraries and target various types of biological molecules using the same basic infrastructure. The standardized well formats, substrates, and detection methods allow the system to handle diverse screening applications without requiring separate complex systems for each assay type.
Solution Approach 2:
The invention optimizes physical parameters such as well size (less than 100 micrometers in diameter), deposit volume, and cell density to achieve single-cell isolation while maintaining assay performance. These parameter optimizations reduce the complexity of cell handling and improve the reliability of single-cell analysis without requiring overly sophisticated equipment.
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 significantly reduces screening time, enhances efficiency, and allows for the rapid identification and recovery of cells producing specific antibodies or cytokines, facilitating the development of new therapies and vaccines.
Implementation Method 1
a moldable slab with microwells enables high-throughput analysis and detection of associations between secreted products and target ligands
Implementation Method 2
exposing a first species comprising an unknown cell-derived, e.g., secreted, product, transferred from the conformable support to the substrate
Implementation Method 3
Optionally, the printed microarray comprises a capture ligand, e.g., which binds to a single immunoglobin isotype
Implementation Method 4
to determine if the first species and the second species associate
Data Source
AI summary
Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.